Cellular and Molecular Biology

Interplay of clinical biomarkers in allergic asthma diagnosis and severity: A case-control study

Zainab Khaleel Mohammed, Shukur Wasman Smail, Christer Janson, Kawa Amin — Thu, 06 Jun 2024 00:00:00 +0200

Given asthma’s large phenotypic diversity, the study was aimed to use specific biomarkers to characterize Allergic asthma (AA) and its severity. Blood was collected from 42 healthy controls (HCs) and 96 patients with AA. Biomarkers related to blood cell number and function: total leukocyte count (TLCs), neutrophil, lymphocyte, monocyte, eosinophil, basophil, neutrophil-to-lymphocyte ratio (NLR), immunoglobulin E (IgE), tryptase and eosinophilic cationic protein (ECP) as well as remodelling biomarkers (Matrix metalloproteinase (MMP-9), (MMP-16), Fibroblast growth factor (FGF-18) and (FGF-23) and alpha-skeletal muscle actin-1 (ACTa-1) were measured. Significant differences were observed in hematological parameters with higher levels of total leukocytes, eosinophil, and basophil counts in the AA group compared to HCs. The disease group also had significantly higher levels of several serum biomarkers (IgE, TPs, ECP, MMP-9, MMP-16, FGF-18, FGF-23, and ACTa-1) compared to HC. Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) had a strong negative correlation with ECP, IgE, and ACTa-1. FEV1 was negatively correlated with MMP-16 and tryptase. Patients with AA have higher levels of several biomarkers, such as MMP-9, MMP-16, FGF-18, FGF-23, IgE, tryptase, and ACTa-1. In addition, IgE, tryptase, ACTa-1, and MMP-16 are related to lung function impairment in AA. This indicates that measuring multiple biomarkers may be of value in the future when diagnosing and monitoring AA.

Circular RNA Circ_0001322 inhibits gastric cancer progression by modulating the miR-1264/QKI axis and suppressing the Hedgehog pathway

Wenyi Wu, Yiqi Cai, Jinji Jin, Zhejing Chen, Mujian Teng — Thu, 06 Jun 2024 00:00:00 +0200

Circular RNA hsa_circ_0001322 (circ1322) was demonstrated to be significantly reduced in expression in gastric cancer patients in our previous study, and changes in its expression were significantly correlated with lymph node metastasis. However, the underlying workings of circ1322 in gastric cancer are still not fully understood. Therefore, to confirm the effect of circ1322 on gastric cancer, we examined the expression of circ1322 in gastric cancer cells and tissues. The results showed that circ1322 was lowly expressed in GC tissues and cells. Subsequently, we further performed cellular assays and animal experiments, which showed that Circ1322 upregulation inhibited GC cell proliferation, migration and invasion. while promoting GC cell apoptosis, and inhibited tumor growth in mice. The direct targeting of circ1322 to miR-1264 was confirmed by bioinformatics prediction and validation of luciferase reporter gene assay. Circ1322 can act as a miR-1264 sponge to alleviate the inhibitory effect of miR-1264 on its target gene, QKI. miR-1264 regulates the expression of QKI and the activity of the hedgehog pathway. That is, circ1322 may act as a competing endogenous RNA (ceRNA) to inhibit the hedgehog pathway by targeting the miR-1264/QKI axis, which in turn promotes GC progression.

A novel gain-of-function mutation in transient receptor potential C6 that causes podocytes injury

Min Yu, Jian Hu, Tao Ju, Ren Wang, Meiqiu Wang, Chunlin Gao, Zhengkun Xia — Thu, 06 Jun 2024 00:00:00 +0200

Podocyte injury plays a vital role in focal segmental glomerulosclerosis (FSGS), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is highly expressed in podocytes and mutations mediate podocyte injury. We found TRPC6 gene mutation (N110S) was a new mutation and pathogenic in the preliminary clinical work. The purpose of this study was to investigate the potential mechanism of mutation in TRPC6 (TRPC6-N110S) in the knock-in gene mouse model and in immortalized mouse podocytes (MPC5). Transmission electron microscopy was used to evaluate renal injury morphology. We measured 24-hour urinary albumin-to-creatinine ratios and major biochemical parameters such as serum albumin, urea nitrogen, and total cholesterol. The results of CCK-8 assay and apoptosis experiments showed that the TRPC6-N110S overexpression group had slower proliferative activity and increased apoptosis than the control group. FluO-3 assay revealed increased calcium influx in the TRPC6-N110S overexpression group. Podocin level was decreased in TRPC6-N110S group, while TRPC6 and desmin levels were increased in TRPC6-N110S group. The 24 h uACR at 6 weeks was significantly higher in the pure-zygotes group than in the WT and heterozygotes groups, and this difference was found at 8 and 10 weeks.TRPC6 levels showed no significant difference between homozygote and WT mice. Compared to homozygote group, expression of podocin and nephrin were increased in WT, but levels of desmin was decreased in WT. Our results suggest that this new mutation causes podocyte injury probably by enhancing calcium influx and podocyte apoptosis, accompanied by increased proteinuria and decreased expression of nephrin and podocin.

Reversal of lipopolysaccharide-induced cardiomyocyte apoptosis via α7nAChR by dexmedetomidine

Mingjing Feng, Changlu Zheng, Xiangyun Li, Baozeng Chen, Weiwei Li — Thu, 06 Jun 2024 00:00:00 +0200

This study aims to analyze the reversal of lipopolysaccharide (LPS)-induced cardiomyocyte apoptosis via α7nAChR by dexmedetomidine (Dex), so as to provide references for clinical treatment of myocardial disorders in the future. First, the research team divided cardiomyocytes (H9C2) were divided into a control group (normal culture), an LPS group (LPS-induced injury model), and an experimental group (pretreated with Dex before LPS induction). Subsequently, lactate dehydrogenase (LDH) and cell activity were detected, and the research team found that the LDH content of the control, experimental and LPS groups were in ascending order (P<0.05). The cell viability decreased and apoptosis increased in the LPS group, with cells mainly concentrating in the G2-M phase; the viability increased and apoptosis decreased in the experimental group, with blocked G1-G0 phase (P<0.05). This demonstrates that Dex can reverse LPS-induced apoptosis in cardiomyocytes. Subsequently, the research group also detected the expression of α7nAChR and NF-κB/AKT pathway, and it was seen that the expression of α7nAChR in the LPS group was higher than that in the control group, with activated NF-κB/AKT pathway; the α7nAChR expression in the experimental group was further elevated, but the NF-κB/AKT pathway was inhibited (P<0.05). The effects of Dex on cardiomyocytes were seen to be related to the α7nAChR and NF-κB/AKT pathways.

Antagonistic and enzymatic activities of Bacillus species isolated from the fish gastrointestinal tract as potential probiotics use in Artemia culture

Thu, 06 Jun 2024 00:00:00 +0200

Probiotics have been used successfully in aquaculture to enhance disease resistance, nutrition, and/or growth of cultured organisms. Six strains of Bacillus were isolated from the intestinal tracts of fish and recognised by conventional biochemical traits. The six isolated strains were Bacillus cereus and Bacillus subtilis using MALDI-TOF-MS technique. The probiotic properties of these Bacillus strains were studied. The tested bacillus strains exhibit antibacterial activity against the different pathogens. The strain S5 gave the important inhibition zones against most pathogens (20.5, 20.33, 23, and 21 mm against Vibrio alginolyticus, Vibrio parahaemolyticus, Staphylococcus aureus, and Salmonella typhimurium, respectively). According to our results, all Bacillus strains have extracellular components that can stop pathogenic bacteria from growing. The enzymatic characterization showed that the tested strains can produce several biotechnological enzymes such as α-glucosidase, naphtol-AS-BI-Phosphohydrolase, esterase lipase, acid phosphatase, alkaline phosphatase, amylase, lipase, caseinase, and lecithinase. All Bacillus strains were adhesive to polystyrene. The adding Bacillus strains to the Artemia culture exerted significantly greater effects on the survival of Artemia. The challenge test on Artemia culture showed that the protection against pathogenic Vibrio was improved. These findings allow us to recommend the examined strains as prospective probiotic options for the Artemia culture, which will be used as food additives to improve the culture conditions of crustacean larvae and marine fish.

Effects of NEAT1 levels on cardiovascular events and prognosis in diabetic nephropathy patients undergoing peritoneal dialysis

Mengjiang Liu, Zhaodan Yan, Yi Zhang, Shengli Zhang — Thu, 06 Jun 2024 00:00:00 +0200

The purpose of this study was to provide observational indicators for clinically predicting cardiovascular events in patients with diabetic nephropathy (DN) undergoing peritoneal dialysis by determining the effects of nuclear enriched abundant transcript 1 (NEAT1) levels on the cardiovascular events and prognosis in DN patients receiving continuous ambulatory peritoneal dialysis (CAPD). A retrospective analysis was conducted on the data of 80 DN patients undergoing CAPD. Patients were assigned to NEAT1 high expression group and NEAT1 low expression group. NEAT1 had a substantially increased expression in the serum of DN patients, and it could serve as a potential biomarker for predicting the development of DN. Patients with highly expressed NEAT1 had an higher level of high-sensitivity C-reactive protein (hs-CRP), larger cardiac structural parameters left ventricular end-diastolic diameter (LVED), left ventricular end-systolic diameter (LVESD), interventricular septal diameter (IVSD) and left ventricular posterior wall diameter (LVPWD), but a notably lower cardiac function evaluation indicator left ventricular ejection fraction (LVEF) than those with lowly expressed NEAT1. The coefficient (r) of correlation between NEAT1 and hs-CRP level was 0.3585 (P=0.0011). The incidence rates of acute myocardial infarction, congestive heart failure and angina in NEAT1 high expression group were higher than those in NEAT1 low expression group. Patients with NEAT1 high expression exhibited a higher mortality rate than NEAT1 low expression group. With the increase in NEAT1 levels, the level of hs-CRP rose in DN patients undergoing CAPD. A higher expression level of NEAT1 indicates poorer cardiac function, higher incidence rates of cardiovascular adverse events and a poorer prognosis in diabetics undergoing CAPD.

Evaluation of a pleiotropic cytokinin polymorphism with cerebral infarction in a Chinese male population

Fengjie Liu, Yun Sun — Thu, 06 Jun 2024 00:00:00 +0200

Cardiovascular diseases, particularly stroke, are a leading cause of morbidity and mortality worldwide. Genetic variations in genes associated with inflammation have been implicated in the pathogenesis of stroke. Interleukin-6 (IL-6), a pleiotropic cytokine with diverse biological functions, has been linked to cardiovascular diseases and stroke. The relationship between cerebral ischemia and inflammation is well-established, suggesting a potential role for IL-6 polymorphisms in stroke susceptibility. In the context of this study, the focus is on evaluating a pleiotropic cytokinin polymorphism, specifically IL-6-572GC, and its association with cerebral infarction in a Chinese male population. The investigation aims to elucidate the genetic correlation between IL-6 polymorphisms and stroke risk, particularly in the context of hemorrhagic subtype of stroke. The study utilizes a case-control design, comparing stroke patients with healthy controls while adjusting for classic risk factors associated with stroke. The methodology employed includes the detection of IL-6 polymorphisms using Real Time Taq Man Probe and PCR-RFLP methods. The results suggest an association between the IL-6-572GC genotype and an increased risk of stroke, particularly in the hemorrhagic subtype. However, the relationship between another IL-6 polymorphism, IL-6-174GC, and stroke remains inconclusive, except for a potential correlation with one allele. The findings underscore the potential role of IL-6-572GC genotype as a genetic risk factor for stroke in the Chinese male population under study. Further research involving larger cohorts is warranted to validate these results and clarify the role of IL-6-174GC polymorphism in stroke susceptibility. Understanding the genetic underpinnings of stroke can provide valuable insights for risk assessment and personalized treatment strategies in affected populations.

Electroacupuncture modulates the TLR4-NF-κB inflammatory signaling pathway to attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats

Thu, 06 Jun 2024 00:00:00 +0200

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.

Penehyclidine hydrochloride improves cognitive function of rats with brain injury via CAMP/CREB signaling pathway

Yuting Wang, Wen Zhao, Shuhui Zhu, Liqun Wei — Thu, 06 Jun 2024 00:00:00 +0200

This study explored the impact of penehyclidine hydrochloride on cognitive function in rats with brain injury. Sprague-Dawley rats (n=36) were randomly assigned to sham-operation, model, and penehyclidine hydrochloride groups. Rats in the sham-operation group underwent craniotomy, while the model and penehyclidine hydrochloride groups received brain injury models and interventions with normal saline and penehyclidine hydrochloride, respectively. Specimens were obtained two weeks post-intervention. Neurological deficits were evaluated using Zea-Longa scores, and memory was assessed with the Morris water maze test. ELISA determined brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) content. mRNA expressions of BDNF and NGF were assessed via qPCR, and phosphorylated CREB (p-CREB) protein expression was measured by Western blotting. Compared to the sham-operation group, both model and penehyclidine hydrochloride groups showed increased Zea-Longa scores. Escape latencies were longer and platform crossings were fewer in model and penehyclidine hydrochloride groups compared to the sham-operation group, but penehyclidine hydrochloride demonstrated a shorter latency and more platform crossings than the model group. BDNF and NGF content decreased in model and penehyclidine hydrochloride groups compared to the sham-operation group, with an increase in the penehyclidine hydrochloride group compared to the model group. mRNA expression levels declined in model and penehyclidine hydrochloride groups but were higher in the latter. p-CREB protein expression was lower in model and penehyclidine hydrochloride groups compared to the sham-operation group but higher in the penehyclidine hydrochloride group than the model group. Penehyclidine hydrochloride exhibited neuroprotective effects by upregulating the cAMP/CREB signaling pathway, improving cognitive function in rats with brain injury.

Molecular diagnosis of hen eggs microbiota

Mohamed Ahmed, Ahmed Al-Hejin, Sana Alattasa, Saleh Al Karaim — Thu, 06 Jun 2024 00:00:00 +0200

The study was conducted in the Kingdom of Saudi Arabia from 2020 and 2022. The identification, characterization, and evaluation of microbes found in hen eggs was done and it was found very important to prevent contamination caused by various harmful pathogenic microbes. It was found that contaminated eggs harbor various harmful microbes which affect health due to multiple infectious diseases. Hen eggs contain a wide variety of microbes, and several distinct approaches were utilized as well as available for achieving detailed pathogenic information. The information obtained is highly essential for people who consume eggs as a food product. It is of the utmost importance to protect people from getting sick due to the consumption of contaminated eggs or eggs from chickens that have been infected by various harmful pathogens. During the experiment, we found that eggs were contaminated directly or the chicken that laid the egg was contaminated. Using molecular genetic analysis, it is possible to detect pathogenic and non-pathogenic contaminations in eggs. During present studies, the cutting-edge molecular techniques of 16S rRNA gene sequencing technology were used to carry out the objective of performing a molecular identification of the microbial communities infecting eggs. The present research is aimed at determining whether the microbial communities in hen eggs are harmful to humans. The results further indicated most bacteria have the potential to cause illness in humans including Escherichia fergusonii, Salmonella enterica, Pseudocitrobacter faecalis, Yakenella regensburgei, and Erwinia pyrifoliae. Further, research suggested that eggs need to be properly cooked and thoroughly washed to eliminate the possibility of consuming infected eggs.

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma

Thu, 06 Jun 2024 00:00:00 +0200

In order to explore a new mode for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), 31 cases of AITL and 28 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) were used as the study subjects. Identifying T follicular helper (TFH) cells with CD4, CD10, Bcl-6, and PD-1, identifying proliferative B cells with CD20 and EZH2, identifying proliferative follicular dendritic cells (FDCs) with CD21 and CD23, and analyzing the value of TFH/B/FDC proliferation and immunolocalization in the diagnosis of AITL. (1) Outside the inherent lymphoid follicles, simultaneous proliferation of TFH/B/FDC (a new diagnostic mode) were observed in AITL [83.87%; 26/31], with their immunolocalizations in the same site [83.87%; 26/31], while this phenomenon was not observed in 28 cases of PTCL-NOS (P<0.05). (2) The sensitivity and specificity of using this new mode to diagnose AITL were both high (83.87%, 100%), which was superior to CD2 (100%, 0%), CD3 (100%, 0%), CD4 (100%, 32.14%), CD5 (100%, 25%), CD10 (61.9%, 100%), Bcl-6 (42.86%, 100%), PD-1 (83.87%, 96.43%), and its Youden Index (0.84) was the highest. The areas under the curve (AUC) of CD10, Bcl-6, PD-1, and new mode to diagnosis AITL were 0.81, 0.71, 0.90, and 0.92, respectively, while the new mode had the highest AUC. The simultaneous proliferation of TFH/B/FDC cells outside the inherent lymphoid follicles can be used to assist in the diagnosis of AITL, and the simultaneous spatiotemporal proliferation of TFH/B/FDC cells is a specific immunomorphology of AITL.

EGFR/TKIs induce excessive apoptosis of bladder carcinoma cells by arresting cell cycle and promoting mitochondrial peroxidation damage

Xiaodong Yu, Bo Liao, Zhongbo Du, Pingyu Zhu — Thu, 06 Jun 2024 00:00:00 +0200

In recent years, bladder carcinoma (BC) has shown an increasing incidence, with poor patient outcomes. In clinical practice, BC is still mainly treated by surgery combined with chemoradiotherapy. However, as chemotherapy resistance of tumor cells becomes more and more obvious, it is urgent to find more effective BC treatment regimes. With the increasing application and growing attention paid to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in various neoplastic diseases, EGFR-TKIs have been considered as a new treatment direction in the future. In this study, the research team used AG1478, an EGFR-TKI, to intervene with the BC cell line T24. It was found that the cell activity was statistically decreased, the apoptosis was enhanced, and the cells were dominantly arrested in the G0/G1 phase, confirming the future therapeutic potential of EGFR-TKIs in BC. Besides, the research team further observed that AG1478 also promoted pyroptosis in T24 cells, and its mechanism is related to the induction of mitochondrial oxidative stress damage. The findings lay a more reliable foundation for the future application of EGFR-TKIs in BC.

Effect of high-flux hemodialysis plus compound-α Ketoacid tablets under humanistic care on calcium-phosphorus metabolism in uremia patients

Yafeng Shi, Shanshan Zhuang, Leibin Hu, Yaping Weng — Thu, 06 Jun 2024 00:00:00 +0200

Uremia (UR) is a terminal renal failure manifestation with a very high risk of death, high-flux hemodialysis (HFHD) is currently the most common treatment for UR in clinical practice. In this study, we analysed the therapeutic efficacy of HFHD plus Compound-α Ketoacid Tablets for UR under humanistic care. Firstly, we randomised 100 patients with UR into a research group (RG) for HFHD plus Compound-α Ketoacid Tablets therapy and a control group (CG) for HFHD treatment, with both therapies implemented under humanistic care. By way of comparison, we found that the study group had significantly better renal function after treatment and they had a lower inflammatory response. Also, the study group showed lower calcium and phosphorus metabolism and better immune function. Based on these results, we believe that HFHD + Compound-α Ketoacid Tablets under humanistic care have high clinical value.

Clinical effect of external ventricular drainage under intracranial pressure monitoring in the treatment of aneurysmal subarachnoid hemorrhage patients and investigation of the mechanism of miR-146a-5p/STC1 axis in inhibiting early brain injury in aneurys

Changqiang Wang, Jingjing Sun, Junling Liu — Thu, 06 Jun 2024 00:00:00 +0200

Aneurismal subarachnoid hemorrhage (aSAH) is a common disease in the neural system, with high death rate. Our study aimed to explore the clinical effect of external ventricular drainage under intracranial pressure monitoring in the treatment of patients with aSAH and investigate the role along with mechanism of miR-146a-5p in aSAH. Ninety-six aSAH patients were allocated into control group (CG) and study group (SG). The CG was released by lumbar puncture. The SG underwent external ventricular drainage based on intracranial pressure monitoring. The prognosis, daily living ability, neurological function, S100β and NSE (neuron-specific enolase) levels and incidence of complications were monitored. Besides, a rat model of SAH was built to assess the neurobehavioral function, blood-brain barrier permeability, brain water content, neuronal apoptosis as well as inflammation. SAH cell model stimulated by oxyhemoglobin, and cell apoptosis as well as inflammation were measured. Luciferase reporter assay was implemented to explore the interaction between miR-146a-5p and STC1. Results showed higher GOS and BI scores but lower NIHSS scores, S100β and NSE levels and complication rates in SG compared with CG. Additionally, miR-146a-5p presented down-regulation in brain tissues of SAH rat model, and overexpressed miR-146a-5p reduced brain injury along with neuroinflammation in SAH rat model. Oxyhemoglobin-induced nerve cell apoptosis along with inflammation after SAH, and overexpressed miR-146a-5p repressed oxyhemoglobin-induced nerve cell apoptosis along with inflammation. STC1 is the target mRNA of miR-146a-5p, and overexpressed miR-146a-5p represses oxyhemoglobin-induced nerve cell apoptosis along with inflammation via regulating STC1 expression. In conclusion, external ventricular drainage under intracranial pressure monitoring could promote prognosis, promote daily living ability, improve neurological function, reduce S100β protein and NSE levels, and reduce the incidence of complications in patients with aSAH. Meanwhile, miR-146a-5p inhibited early brain injury and neuroinflammation in aSAH via regulating STC1 expression.

The characteristics of the novel bacterial strain Pseudomonas mendocina isolated from freshwater aquaculture farm

Kai Yan, Shuai Wei, Haifeng Wang — Thu, 06 Jun 2024 00:00:00 +0200

Plastic contamination can cause damage to the water quality of fish farm ponds, and also affect the quality of the final product. Pseudomonas mendocina was found to biodegrade plastics. Our study aimed to investigate the physicochemical properties and drug resistance of P. mendocina isolated from local freshwater aquaculture farms. Firstly, the strain was isolated from aquaculture water and then identified by matrix-assisted flight mass spectrometry and 16S rDNA sequencing. Then, biochemical and antibiotic resistance analyses were performed, and a microbial high-throughput growth detector was used to assess the growth of the strain. Finally, PCR and proteomics analyses were conducted to determine drug-resistance-related genes/proteins. According to the results of the spectrum diagram and sequencing, the isolated bacteria were identified as P. mendocina, and were positive for reactions of ADH, MTE, LAC, MNE, FRU, CIT, MLT, ONPG, and ACE. P. mendocina was sensitive to most of the antibiotics, and its resistance to CHL, MIN, and TIC/CLA was intermediate. Additionally, gyrB was the resistance gene, and mdtA2, mdtA3, mdaB, and emrK1 were closely related to the drug resistance of P. mendocina. Our results show the biochemical properties of P. mendocina in isolated aquaculture water, and provide a new perspective for P. mendocina involved in the biological removal of plastics or microplastics in freshwater aquaculture farms.

Expression of CD109 in oral squamous cell carcinoma and its clinical significance

Hongyu Chen, Junji Xu, Rong Ge, Chuangfeng Liu — Thu, 06 Jun 2024 00:00:00 +0200

The purpose of this study was to investigate the expression of CD109 and its clinicopathological significance in oral squamous cell carcinoma. Data from TIMER2.0 and UALCAN were analyzed to assess CD109 mRNA levels in OSCC. The immunohistochemical method was used to investigate the expressions of CD109 in 20 normal oral mucosa and 75 OSCC and analyzed the relationship between the expression of CD109 and the clinical variables. The mRNA levels of CD109 in OSCC tissues were significantly higher than in adjacent normal tissues (p<0.05). Immunohistochemical analysis revealed that CD109 protein expression was increased in OSCC tissues compared to normal tissues, and this difference was statistically significant (P<0.05). The positive rate of CD109 expression was 94% (16/117) in the group with lymph node metastasis, while it was 55% (32/58) in the group without metastasis (P<0.05). Similarly, the positive rate of CD109 expression was 91% (22/23) in the low differentiation group and 59% (26/52) in the high differentiation group (P<0.05). CD109 expression is markedly higher in OSCC, contributes to the pathological grading of OSCC and predicts lymph node metastasis.

Metabonomics analysis of aqueous humor samples from cataract patients with branch retinal vein occlusion

Thu, 06 Jun 2024 00:00:00 +0200

Cataract (CAT) has a very high incidence rate among the middle-aged and elderly, with most patients complicated by branch retinal vein occlusion (BRVO), a key cause of blindness. In this study, through metabolomic analysis of aqueous humor samples from CAT patients with BRVO, a total of 319 different metabolites were found, most of which belonged to the categories of carboxylic acids and derivatives, fatty acyls, and organooxygen compounds. The most typical metabolites were 3-methylhistidine and biliverdin, which were up-regulated, as well as the down-regulated beta-glycerophosphoric acid. Tricosanoic acid showed the most significant correlation with CAT+BRVO. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the most commonly related keywords for differentially expressed metabolites were biosynthesis of unsaturated fatty acids and synaptic vesicle cycle. These results can not only help to further understand the pathogenesis of CAT complicated by BRVO in clinical practice, but also provide some new therapeutic research directions.

Impacts of Chlorine 1-3 ıon channels on localized bladder neoplasms

Thu, 06 Jun 2024 00:00:00 +0200

Bladder tumors occur more frequently in men than in women and are the fourth most common malignancy after prostate, lung, and colon cancers. In this study, we examined the expression of chlorine ion channel 1 and chlorine ion channel 3 in localized bladder tumors according to their stage. We conducted a retrospective analysis of a prospective cohort study spanning from May 2018 to January 2020. This study involved a group of 55 patients who had been diagnosed with primary bladder cancer and underwent transurethral resection of bladder tumor under either general or spinal anesthesia. In addition, 30 patients who underwent cystoscopy due to etiology of hematuria and biopsies were taken from suspicious areas and whose results were normal were included as the control group. The collected samples were evaluated using real-time polymerase chain reaction in a medical genetics laboratory. In our study, it was observed that chlorine ion channel 3 gene expression increased significantly (P<0.001) in all cancer tissues compared to the control group, whereas no significant increase was found in chlorine ion channel 1 gene expression compared to the control group. The data obtained, especially for chlorine ion channel 3, are promising in terms of their use in the treatment of bladder tumors in humans.

High expression of HMBOX1 promotes the progression of lung squamous cell carcinoma

Xiao Chen, Guiming Zha, Chuanchen Li, Kangwu Wang — Thu, 06 Jun 2024 00:00:00 +0200

This study aimed to explore the expression of homeobox-containing 1 (HMBOX1) and its clinical significance in lung squamous cell carcinoma (LSCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of HMBOX1 in LSCC tissues. The relationship between HMBOX1 expression and clinical pathological data was analyzed by Chi-square or Fisher’s exact test. Furthermore, the role of HMBOX1 in LSCC in vitro was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry and Western blot (WB) assays. HMBOX1 was highly expressed in LSCC tissues when compared with para-cancer tissues (P<0.05). According to the median expression of HMBOX1, the patients were divided into two groups, including high-expression group and low-expression group. HMBOX1 expression was correlated with tumor size, differentiation and clinical stage (P<0.05). Subsequent experiments indicated that LSCC cells with low expression of HMBOX1 exhibited significantly inhibited proliferation, G0/G1 block and promoted apoptosis (P<0.05). HMBOX1 expression was positively correlated with the expression of VEGF, elaborating that HMBOX1 probably promoted the growth of LSCC cells by affecting VEGF. HMBOX1 might contribute to the development of LSCC.

Effect of collagen sponge combined with epidermal growth factor in repairing maxillofacial head and neck wounds in rats

Qian Wang, Zhiyi Wei, Tianlai Lin, Yazhen Huang — Thu, 06 Jun 2024 00:00:00 +0200

Collagen sponge and epidermal growth factor (EGF) promote wound healing. However, the effect of collagen sponge combined with EGF in repairing maxillofacial head and neck wounds remains unclear. The rats were divided into 3 groups, including experimental group 1 (Vaseline gauze+EGF), experimental group 2 (collagen sponge+EGF) with control group (Vaseline+normal saline), and maxillofacial head and neck wounds were simulated. Wound pathological morphology was detected by HE staining; wound EGF, IL-1β, IL-6 along with TNF-α contents by ELISA and MMP1 level by western blot. At 7 and 14 days after treatment, wound healing rate of two experimental groups was higher than that of control group, and that of experimental group 2 presented higher than that of experimental group 1. Compared with control group, experimental group 1 had significantly fewer inflammatory cells in the wound tissue, local erythrocyte spillage outside the vascular walls, more collagen deposition and more granulation tissue. Compared with experimental group 1, inflammatory cells in wound tissues of experimental group 2 were significantly reduced, the collagen tissues were visible and arranged, and the growth of the wound granulation tissue was obvious. IL-1β, IL-6 along with TNF-α levels in two experimental groups presented lower than control group, and EGF level was higher. More importantly, in contrast to experimental group 1, IL-1β, IL-6 along with TNF-α in experimental group 2 presented lower, and EGF level presented higher. At 14 days after treatment, MMP1 level in two experimental groups was lower than control group. In contrast to experimental group 1, MMP1 level in experimental group 2 was lower. In summary, collagen sponge combined with EGF for the first time significantly improved the healing speed of maxillofacial head and neck wounds and reduced the scar left after wound healing.

A20 promoted the phagocytosis of lymphoma cells by dendritic cells from activated B-cell-like non-Hodgkin lymphoma

Thu, 06 Jun 2024 00:00:00 +0200

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13⁺CD117^-, CD56⁺CD40⁺ and CD23⁺CD40⁺ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c⁺CD123^-DCs and the percentage of CD56⁺mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.

17β-estradiol activates SOX6 to balance the anabolism and catabolism via estrogen receptor 2 in chondrocyte

Ying Cao, Yongji Li, Xiangjun Yang, Hongxu Wang, Hongpeng Liu — Thu, 06 Jun 2024 00:00:00 +0200

We investigated the influence of 17β-estradiol (17β-E2) on cartilage extracellular matrix (ECM) homeostasis in postmenopausal women. We focused on the roles of estrogen receptors (ESR) and SOX6 in 17β-E2-mediated stimulation of ECM metabolism during chondrocyte (CH) degeneration. We compared the expression of anabolic genes (collagen II and aggrecan) and catabolic genes (MMPs and TIMPs) in IL-1β-induced CH degeneration in vitro, with and without 17β-E2 supplementation. We separately silenced the SOX6, ESR1, and ESR2 genes in CHs to determine their impact on 17β-E2 treatment. Additionally, we used Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and luciferase assays to investigate protein-DNA interactions within ESR2 and SOX6-promoter complexes. After three days of IL-1β treatment, ESR1/2, SOX6, collagen II, aggrecan, and TIMP1/3 were decreased, while MMP3/9/13 were increased. The addition of 17β-E2 partially reversed these effects, but silencing SOX6, ESR1, or ESR2 weakened the protective effects of 17β-E2. Silencing ESR2, but not ESR1, abolished the upregulation of SOX6 induced by 17β-E2. ESR2 was found to bind the SOX6 promoter and regulate SOX6 expression. 17β-E2 upregulates SOX6 through ESR2 mediation, and the synergistic effect of 17β-E2 and ESR2 on SOX6 balances ECM metabolism in CHs.

Overexpression of CISD2 alleviates septic acute kidney injury via activating Sonic Hedgehog signaling pathway

Wenjun Wu, Jia Zhang, Fei Chen, Hongzhuan Song, Xiujie Zhou — Thu, 06 Jun 2024 00:00:00 +0200

Patients with sepsis are often complicated by acute kidney injury (AKI), which greatly increases mortality. In this study, our purpose was to explore the expression and function of CDGSH iron sulfur domain 2 (CISD2) in septic AKI, and the underlying molecular mechanism. Western blot and quantitative real-time polymerase chain reaction (RT-PCR) were employed to detect protein and mRNA levels in cells. The inflammation level of cells was evaluated by detecting the content of inflammatory factors (TNF-α, IL-1β, IL-6). Apoptosis of cells was evaluated by Caspase-3 activity assay, flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL) staining. CISD2 was down-regulated in HK-2 cells treated with lipopolysaccharide (LPS). LPS treatment increased the level of inflammatory factors, the activity of Caspase-3, and the rate of apoptosis in HK-2 cells. However, overexpression of CISD2 significantly suppressed these effects. Moreover, overexpression of CISD2 activated the Sonic Hedgehog (SHH) signaling pathway. The use of cyclopamine (Cyc), a SHH signaling pathway inhibitor, eliminated the effect of overexpressing CISD2, that is, inhibiting LPS-induced inflammation and apoptosis of HK-2 cells. LPS treatment down-regulated CISD2 in HK-2 cells, and overexpression of CISD2 could inhibit LPS-induced inflammation and apoptosis of HK-2 cells by activating the SHH signaling pathway.

Improving the anti-diabetic and anti-hyperlipidemic activities of extra virgin olive oil by the incorporation of diallyl sulfide

Thu, 06 Jun 2024 00:00:00 +0200

Development of novel functional foods is trending as one of the hot topics in food science and food/beverage industries. In the present study, the anti-diabetic, anti-hyperlipidemic and histo-protective effects of the extra virgin olive oil (EVOO) enriched with the organosulfur diallyl sulfide (DAS) (DAS-rich EVOO) were evaluated in alloxan-induced diabetic mice. The ingestion of EVOO (500µL daily for two weeks) attenuated alloxan-induced elevated glucose, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), urea and creatinine. It also normalized the levels of triglycerides (TG), total cholesterols (TC), low-density lipoprotein-cholesterol (LDL-c) and their consequent atherogenic index of plasma (AIP) in diabetic animals. Additionally, EVOO prevented lipid peroxidation (MDA) and reduced the level of hydrogen peroxide (H2O2) in diabetic animals. Concomitantly, it enhanced the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), reducing thereby tissue oxidative stress injury. The overall histologic (pancreas, liver, and kidney) alterations were also improved after EVOO ingestion. The manifest anti-diabetic, lipid-lowering and histo-protective properties of EVOO were markedly potentiated with DAS-rich EVOO suggesting possible synergistic interactions between DAS and EVOO lipophilic bioactive ingredients. Overall, EVOO and DAS-rich EVOO show promise as functional foods and/or adjuvants for the treatment of diabetes and its complications.

Clinical implications and mechanism of CST1 in gastric carcinoma based on database screening

Peng Liu, Jiusong Luan, Xinyu Peng, Xiu Zhang, Jianjun Zhang, Haizhe Chang — Thu, 06 Jun 2024 00:00:00 +0200

Gastric cancer (GC) remains one of the most common malignant tumours worldwide, with extremely high morbidity and mortality rates. An in-depth understanding of the pathogenesis of GC is key to the future diagnosis and treatment of GC. In this study, we analysed the differentially expressed genes (DEGs) in gastric carcinoma (GC) through GEO database and their clinical implications, with the aim of providing clinical reference and guidance. We selected the GSE118916 dataset for bioinformatics analysis and identified a total of 3231 DEGs. Keywords, including extracellular region, vesicle, protein digestion and absorption, ECM-receptor interaction, etc., of DEGs can be seen by the GO and KEGG enrichment analysis. The online database determined up-regulated CST1 in GC and some other tumors, as well as a close connection between CST1 with patient prognosis. Subsequently, we collected a number of GC clinical cases and examined the expression of CST1, which was seen to be highly expressed in GC, with a favorable diagnostic effect on the occurrence of GC (P<0.05) and a strong correlation with TNM stage, tumor invasion, tumor diameter and differentiation (P<0.05). In other words, CST1 is closely related to the occurrence and development of GC, and has the potential to be a breakthrough in the diagnosis and treatment of GC in the future.

Study on the mechanism of Huangqi Guizhi Wuwu Decoction in treating diabetes peripheral neuropathy based on network pharmacology and molecular docking

Bichen Ai, Weihua Zhang, Guojing Li — Thu, 06 Jun 2024 00:00:00 +0200

This study aimed to explore the effective substances and mechanism network of Huangqi Guizhi Wuwu Decoction in treating diabetes peripheral neuropathy. Based on the TCM systemic pharmacological analysis platform (TCMP) and UniProt database, the database of active Huqarqu Decoction was constructed, and the related targets of diabetic peripheral neuropathy were collected through the OMIM, CTD, DisGeNET, TTD and GeneCards databases. The intersection targets were obtained to construct the network diagram of Huangqi dis Guizhi Wuwu Decoction-Active Through the String database, the interaction between target proteins was analyzed, and molecular docking between active components and potential targets was carried out. Combined with the DAVID v6.8 database, GO function analysis and KEGG pathway analysis were performed on the targets. Guizhi Wuwu Decoction mainly acts on core targets such as IL6, MAPK3, VE GFA, JUN and ESR1 through quercetin, kaempferol and naringin and regulates the TNF signaling pathway, estrogen signaling pathway and MAPK signaling pathway, thus achieving the effect of treating diabetes peripheral neuropathy. Huangqi Guizhi Wu has multiple targets and regulates multiple signaling pathways in neuropathy, which lays a foundation for future pharmacological research.

Network pharmacology and transcriptomics analysis reveal the mechanism of BushenHuoxue formula attenuates premature ovarian failure via modulation PI3K/AKT pathway

Thu, 06 Jun 2024 00:00:00 +0200

This study aims to analyze the active components and mechanism of Bushen Huoxue (BSHX) formula on the autoimmune premature ovarian insufficiency (POI) by combining network pharmacology and Transcriptomics. The active components and targets of BSHXF were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). POI-related targets were identified through Therapeutic Targets Database (TTD), DisGeNET and drugbank database. The Veen diagram was performed to obtain the action targets. The active compound-target network and Protein-Protein Interaction (PPI) network were built by using STRING database and Cytoscape software. Key targets and active compounds were further identified by topological analysis. Molecular docking shows that Kaempferol, Isorhamnetin and Anhydroicaritin have strong binding to AKT. Finally, a zp3-induced autoimmune ovarian function deficiency mouse model was used to explore the potential mechanism of POI. The potential pathways of BSHXF for the treatment of POI were identified by Transcriptomic analysis. PI3K-AKT and NF-kb pathways were the common pathways between network pharmacology and transcriptomics. Our results revealed that BSHXF could reduce the FSH expression levels and raise the E2, and AMH levels in the serum. Western bloting demonstrates that BSHXF could upregulate the expression of p-PI3K and p-AKT.

Inhibition of histone deacetylases class I improves adipogenic differentiation of human periodontal ligament cells

Thu, 06 Jun 2024 00:00:00 +0200

Periodontal ligament stem cells (PDLSCs) show plasticity towards the adipogenic lineage; however, little has been done on the participation of epigenetic mechanisms. Histone acetylation is a dynamic process, though balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) activities. This process can be halted by HDACs inhibitors, such as trichostatin A (TSA) and valproic acid (VPA). This study aimed to determine the role of HDACs class I in adipogenic differentiation of PDL cells. PDLSCs were treated with TSA at concentrations of 100, 200, and 250 nM, or VPA at 1, 4 and 8 mM. Cell viability was assessed using MTT assays. Gene expression of pluripotency markers (NANOG, OCT4, SOX2), HAT genes (p300, GCN5), and HDACs genes (HDAC1-3) was analyzed by RT-qPCR. Adipogenic differentiation was evaluated via oil red O staining, and acetylation of histone H3 lysine 9 (H3K9ac) was examined by Western blot. VPA treatment resulted in a 60% reduction in cell proliferation, compared to a 50% when using TSA. Cell viability was not affected by either inhibitor. Furthermore, both TSA and VPA induced adipogenic differentiation, through an increase in the deposition of lipid droplets and in GCN5 and p300 expression were observed. Western blot analysis showed that TSA increased H3K9ac levels on adipogenic differentiation of PDLSCs. These findings highlight the potential of HDAC inhibitors as a tool for modulating H3K9 acetylation status and thus influencing adipogenic differentiation of PDLCs.

Molecular mechanism of the influence of related genes expression in synovium tissue around shoulder joint of secondary frozen shoulder model rats on angiogenesis

Jie Xu, Dong Ren, Fei Liu, Shuren Liu, Pengcheng Wang — Thu, 06 Jun 2024 00:00:00 +0200

The study aimed to explore the pathogenesis of secondary frozen shoulder and its influence on synovium tissue and angiogenesis by constructing a rat secondary frozen shoulder model along with transforming growth factor. 40 healthy male rats aged 8 weeks were divided into Sham group (n=10, no modeling treatment), Control group (n=10, modeling treatment), Low group (n=10, modeling treatment, and 10 mL/d transforming growth factor), and High group (n=10, modeling treatment, and 20 mL/d transforming growth factor). Hematoxylin and Eosin (HE) method was used for histological detection, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining method were adopted to detect the expression of Matrix metalloproteinase-14 (MMP-14), mitogen-activated protein kinase (p38MAPK), and Vascular endothelial growth factor (VEGF). Compared with Sham group, the range of abduction and external rotation of rat glenohumeral joint in Control group, Low group, and High group was significantly reduced, and High group had the smallest range. Compared with the Sham group, the synovium in the Control group, the Low group, and the High group had obvious hyperplasia, and the blood vessels were significantly increased. Immunohistochemical staining and RT-PCR results showed that compared with Sham group, MMP-14, p38 MAPK, and VEGF in Control group, Low group, and High group all increased significantly, among which High group increased most. The secondary frozen shoulder is mainly manifested as synovial hyperplasia and increased blood vessels, which are related to the induction of MMP-14, p38 MAPK, and VEGF by transforming growth factor, which reveals the pathogenesis of secondary frozen shoulder to a certain extent, and lays a foundation for subsequent clinical treatment of secondary frozen shoulder.

Circular RNA circ_0006168 accelerates the development of hepatocellular carcinoma through sponging microRNA-125b

Linjun Zhuang, Chenxin He, Jiawei Gao, Zhaobi Zhu, Changjie Lin, Wei Chen — Thu, 06 Jun 2024 00:00:00 +0200

This study explored the role of circular RNA circ_0006168 in the progression of hepatocellular carcinoma (HCC) and its interaction with microRNA-125b. The expression of circ_0006168 was examined in 42 pairs of HCC tumor and adjacent tissue specimens using quantitative polymerase chain reaction (qPCR). Elevated circ_0006168 expression in HCC tissues was significantly associated with advanced pathological staging and lower overall survival rates. Lentivirus-mediated circ_0006168 knockdown in HCC cell lines (Hep3B and Huh7) demonstrated a notable reduction in cell proliferation and an increase in apoptosis. MicroRNA-125b expression exhibited a marked reduction in HCC tissues, negatively correlating with circ_0006168 levels. Luciferase reporting assays indicated that circ_0006168 was a direct target of microRNA-125b. Additionally, cell recovery experiments suggested a reciprocal regulation between circ_0006168 and microRNA-125b, contributing to the accelerated malignant progression of HCC. The study underscored the significantly increased expression of circ_0006168 in both HCC tissues and cell lines, highlighting its association with advanced pathological stages and poor prognosis in HCC patients. Furthermore, circ_0006168 appeared to play a pivotal role in elevating the proliferation rate of HCC cells through its modulation of microRNA-125b. These findings contribute to a deeper understanding of the molecular mechanisms underlying HCC development and may offer potential therapeutic targets for intervention.

Characterization of chromosomal segment substitution lines developed in the genetic background of rice variety K 343

Thu, 06 Jun 2024 00:00:00 +0200

In this study, BC₃F₂ convergent population [(K343*3/RML22 × K343*3/DHMAS) × K343] was constructed by marker-assisted backcross breeding using K343 as the recurrent parent. DHMAS and RML22 were used as donor parents for the rice blast resistance genes Pi54 and Pi9, respectively. The population was first characterized using GGT 2.0 software, which showed 96.7% of the recurrent genome recovery covering 13953.6 cM, while DHMAS and RML22 showed 1.6% (235.5 cM) and 1.2% (177.1 cM) introgression respectively. The chromosomal segment substitution lines (CSSLs) were then identified using CSSL Finder software. A total of 36 CSSLs were identified, including 22 for DHMAS/K343 and 14 for RML22/K343. Introgression rates for donor substituted segments in DHMAS/K343 CSSLs ranged from 0.54% to 5.99%, with donor coverage of 44.5%, while in RML22/K343 CSSLs, introgression rates ranged from 0.54% to 4.75%, with donor coverage of 24.5%. The identified CSSLs would be a valuable genetic pool and could be used as genomic resources for the discovery and mapping of important genes and QTLs in rice genetic improvement.

Effect of ADSCs on Th17/Treg and T-bet/GATA-3 in model mice with primary immune thrombocytopenia

Haijiao Dong, Zhaoqi Ren, Wen Shao, Guanghua Duan, Bin Du — Thu, 06 Jun 2024 00:00:00 +0200

We aimed to observe the effects of adipose-derived mesenchymal stem cells (ADSCs) on T helper 17 (Th17)/regulatory T cells (Treg) and T-box transcription factor (T-bet)/GATA-binding protein 3 (GATA-3) in model mice with primary immune thrombocytopenia (ITP). 32 BALB/C mice were selected. ADSCs were isolated from 2 mice and cultured. The other 30 mice were randomly divided into the normal control group, the ITP model control group, and the ITP experimental group. Platelet count (PLT), Th17/Treg cells, related serum cytokines [interleukin-6 (IL-6), IL-17A, IL-10, and transforming growth factor β1 (TGF-β1)], T-bet and GATA-3 mRNA levels in peripheral blood mononuclear cells (PBMCs) in the 3 groups were detected. PLT and Treg in the ITP experimental group were significantly lower than those in the normal control group (P<0.05), but significantly higher than those in the ITP model control group (P<0.05). Th17 and Th17/Treg in the ITP experimental group were significantly higher than those in the normal control group (P<0.05), but significantly lower than those in the ITP model control group (P<0.05). Serum IL-6 and IL-17A levels, and T-bet mRNA levels in the ITP experimental group were significantly higher than those in the normal control group (P<0.05), but significantly lower than those in the ITP model control group (P<0.05). Serum IL-10 and TGF-β levels, and GATA-3 mRNA levels in the ITP experimental group were significantly lower than those in the normal control group (P<0.05), but significantly higher than those in the ITP model control group (P<0.05). ADSCs can effectively regulate Th17/Treg balance and improve T-bet/GATA-3 mRNA expression levels in ITP model mice.

Expression of FoxO3a in sepsis mice and its association with lymphocyte apoptosis

Ya Wen, Yan Li, Jinli Guo, Kaijian Shang — Thu, 06 Jun 2024 00:00:00 +0200

This study investigated forkhead box O3a (FoxO3a) expression in peripheral blood of sepsis mice and its correlation with lymphocyte apoptosis. Sixty male C57 mice were randomly assigned to sham, model, and intervention groups. Sepsis was induced via cecal ligation in the model and intervention groups, while sham mice underwent similar procedures excluding cecal ligation. Apoptosis proteins in lymphocytes were assessed by Western blotting, reactive oxygen species (ROS) levels by 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA), and serum interleukin-1β (IL-1β) and IL-10 content. The model group exhibited elevated mortality, increased lymphocyte apoptosis, higher Caspase3 expression, and lower Bcl-2/Bax ratio compared to sham and intervention groups. Additionally, the model group displayed decreased serum IL-10, elevated IL-1β, heightened lymphocytic ROS, reduced FoxO3a expression, and increased levels of p-FoxO3a, p-PI3K, and p-Akt compared to sham. In sepsis mice, inhibited FoxO3a signaling in lymphocytes leads to enhanced apoptosis, elevated ROS, and immune cell dysfunction, contributing to increased mortality.

Toxicology of milrinone by zebrafish embryotoxicity test

Lingfeng Li, Zhen Chen, Zihe Zheng, Xiaofu Dai — Thu, 06 Jun 2024 00:00:00 +0200

Milrinone, a phosphodiesterase III inhibitor with contractile and vasodilatory effects, is widely used in acute decompensated heart failure and medically refractory end-stage heart failure (HF). The adverse reactions of milrinone have been extensively explored clinically, but its possible toxicities and underlying molecular mechanisms in embryo development need further understanding as its clinical applications increase. Herein, we assessed the milrinone toxicity using the zebrafish embryotoxicity test (ZET), with a view of providing evidence and guidance for gravidas medicine. We carried out ZET by exposing embryos to a milrinone culture with a series concentration gradients since 1.5 hours post fertilization (hpf) and observed and assessed mortality and hatching rates of drug-treated zebrafishes at 24, 48, 72, and 96 hpf. No significant lethal effect was found in milrinone-treated zebrafish, but hatching rate of eggs at 48 hpf was up-regulated with the increase of milrinone concentration. The impact of milrinone on embryogenesis was assessed through body length, eye area, yolk sac area, swim bladder inflation area, pericardial area and venous congestion area at 96hpf. 150 μg/mL or higher milrinone treatment showed significant effects in the indicators. Organ disorders including enlarged pericardium, liver atrophy and decreased blood vessels were observed in dysplasia individuals versus controls. TUNEL assay suggested the ability of milrinone to induce apoptosis in malformation embryos. Quantitative real-time PCR showed aberrant expressions of transcription factors associated with heart development and genes related to liver development and apoptosis regulation. Therefore, ZET is feasible for the milrinone toxicity test, and high-dose milrinone causes harm to the embryonic development of zebrafish, especially in embryonic carcinogenesis, vasculogenesis, and hepatogenesis.

Analysis of the mechanism by which ketamine affects astrocytes in Parkinsonian rats through the PI3K/AKT axis

Yanhong Xiong, Jianwen Yuan, Luogeng Xu — Thu, 06 Jun 2024 00:00:00 +0200

Parkinson's disease (PD) remains the most common neurodegenerative disease worldwide, seriously affecting the normal life of patients. Currently, there is no effective clinical cure for PD. In this study, the research team explored the effect of ketamine (KET) on PD, which can lay a reliable foundation for future KET treatment of PD. First, the research team established a PD rat model with 6-hydroxydopamine (6-OHDA). The detection showed that the maximum angle of the inclined plate stay, the number of times of grid crossings and standing, and the ATPase activity in brain tissue were significantly lower in PD rats than in control rats, while the positive rate of α-synuclein in brain tissue was increased, showing typical pathological manifestations of PD. After using KET to intervene in PD rats, the behavioral and brain pathological changes were significantly alleviated, and the inflammation and oxidative stress damage of brain tissue were effectively reduced, suggesting the potential therapeutic effects of KET on PD. Furthermore, the use of KET inhibited the PI3K/AKT axis in the brain tissue of PD rats and promoted autophagy. Moreover, the significant suppression of the PI3K/AKT axis by KET was also demonstrated in the PD cell model established through lipopolysaccharide (LPS) inducement of astrocyte cell line HA1800. It is suggested that the mechanism of KET on PD is related to the inhibition of the PI3K/AKT axis.

N6-Methyladenosine modified circ-NAB1 modulates cell cycle and epithelial-mesenchymal transition via CDKN3 in endometrial cancer

Jun Zhang, Yang Zhang, Jinwei Zhang — Thu, 06 Jun 2024 00:00:00 +0200

Endometrial cancer (EC) is a common malignant tumor in the female reproductive system. Circular RNAs (circRNAs) and N6-methyladenosine (m⁶A) modification are widely involved in cancer progression. Nevertheless, the cross-talk between circ-NAB1 and m⁶A as well as the biological functions of circ-NAB1 in EC remain unclear. Circ-NAB1 was observed to be upregulated in EC tissues and cells by RT-qPCR. MeRIP and RNA pull-down assays were utilized for detecting the m⁶A modification of circ-NAB1. The interaction between circ-NAB1 and RNAs was also detected. Colony formation, transwell, flow cytometry, and western blot were utilized for measuring EC cell behaviors. Mechanically, we proved the m⁶A demethylase alkylation repair homolog protein 5 (ALKBH5) can mediate circ-NAB1 expression through an m⁶A-YTHDF2-dependent manner. Circ-NAB1 overexpression can promote cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and cell cycle through functional assays. Circ-NAB1 knockdown exerts the opposite function on EC cells. Furthermore, we proved that circ-NAB1 can sponge miR-876-3p to upregulate the target gene cyclin-dependent kinase inhibitor 3 (CDKN3) in EC cells. CDKN3 overexpression can reverse the impacts of circ-NAB1 depletion on EC cell behaviors. Collectively, we proved that ALKBH5-mediated m⁶A modification of circ-NAB1 promoted EMT process and cell cycle in EC via targeting the miR-876-3p/CDKN3 axis.

IL-15 gene mutation as a molecular risk factor in acute lymphoid leukemia

Thu, 06 Jun 2024 00:00:00 +0200

The present study investigated the relationship between single nucleotide polymorphisms in the interleukin (IL)-15 gene located (exon 8) on the chromosomal location 4q31.21 and acute lymphoblastic leukaemia (ALL) risk in Iraqi patients. A total of 78 (49 male -29 female) primary ALL (62B-cell, 16 T-cells lineages cases and 30 healthy control subjects (median age 11, age range were 4-21.5), were enrolled at the Nanakaly Hospital of Erbil Province between February 2021 and January 2022. The genotype analysis was performed using polymerase chain reaction (PCR) and Sanger DNA sequencing. The IL15 homozygous rs10833 (100%) and rs2291596 (63.6%) genotypes indicated high frequencies and were associated with a risk of developing ALL, while the remaining 16 novel mutations indicated in low frequency (9.1%) except for the 97270G>GT genotype (18.2%). High expression levels were noted for different clusters of differentiation (CD) biomarkers between both subtypes of ALL, including, CD10, CD19, CD22, CD79a, CD99, terminal deoxynucleotidyl transferase (TdT), and human leukocyte antigen DR (HLA-DR) isotype in B-cells lineages, while, CD2, CD3, CD5, CD7, CD13, CD117 and TdT are more specific to T-cells lineages. On the other hand, significant changes were noted in certain hematological parameters including red blood cells (RBCs), haemoglobin (g/dl), haematocrite (HCt %), red blood cell distribution width (RDW %), and platelet counts (PLT- 10⁹/L) compared with those of healthy subjects. Finally, it was concluded that various novel mutations were recorded with different subtypes of ALL diseases, and mild anemia was observed among patients. Future studies will be towered to associate these mutations with prognosis and therapeutic response of diseases.

Correlation between miR-210 and serum levels of GGT, ALP and AST in patients with choledocholithiasis

Ping Luo, Kun Huang, Diqing Wu, Hui Xu — Thu, 06 Jun 2024 00:00:00 +0200

The purpose of this study was to explore the association between miR-210 and serum GGT, ALP and AST levels in patients with choledocholithiasis. The clinical data of 82 patients with biliary stones admitted to the hospital from May 2020 to May 2022 were collected and divided into observation group (n=40) and control group (n=42) according to whether asymptomatic combined. The relative expression level of miR-210 was measured by RT-PCR, serum GGT, ALP, and AST by rate method, and the correlation of miR-210 expression level with serum GGT, ALP, AST and the diagnostic value for choledochal stones was analyzed. The relative expression of serum GGT, ALP, AST and miR-210 were all higher than the control group (P <0.05); the relative expression level of miR-210 and serum GGT, ALP and AST, 0.756, 0.832, 0.326, r = P <0.05), 0.782, 0.776, 0.681, 0.568, respectively. Serum miR-210 level was upregulated in patients with choledocholithiasis, and its expression was positively correlated with serum GGT, ALP, and AST, which can be used for early auxiliary diagnosis of choledocholithiasis.

Recombinant human growth hormone promotes wound angiogenesis in burned mice through the ERK signaling pathway

Yang Shao, Mei Han, Guoyue Chen, Guodong Song — Thu, 06 Jun 2024 00:00:00 +0200

Burns are the most severe type of trauma, and the resulting ischemia and hypoxia damage can promote the dysfunction and even failure of tissues and organs throughout the body, endangering patients’ life safety. Recombinant human growth hormone (rhGH) has the functions of promoting protein synthesis to reverse negative nitrogen balance, accelerating wound healing, and improving immune function, which is widely used in the treatment of burns. However, the exact mechanism and pathway of rhGH's action is not yet fully understood. In this study, we observed the wound repair effect of recombinant human growth hormone (rhGH) on burned mice and further analyzed the mechanism of action, which can provide more comprehensive reference opinions for clinical practice. First, by establishing a burn mouse model and and intervening with different doses of rhGH, we found that the wound healing capacity of mice was significantly enhanced and the inflammatory and oxidative stress responses were obviously alleviated, confirming the excellent promotion of wound repair and anti-inflammatory and antioxidant effects of rhGH. Subsequently, we found that the expression of p-ERK1/2/ERK1/2, EGF, TGF-β, and VEGF proteins was elevated in the traumatic tissues of mice after rhGH intervention, suggesting that the pathway of action of rhGH might be related to the activation of ERK pathway to promote the regeneration of traumatic capillaries.

Autophagy related genes mediated mitophagy in yeast, mammals and higher plants

Thu, 15 Feb 2024 00:00:00 +0100

Autophagy is classified into macro-autophagy and micro-autophagy. Two major types of autophagy in the complex eukaryotic organism are microautophagy and macroautophagy. During microautophagy, cytoplasmic components that need to be degraded are taken up by lysosomes in animals and by vacuole in yeast and plants via the invagination of tonoplast. While macroautophagy is initiated after the formation of a cup-shaped membrane structure, a phagophore develops at cargo that grows in size and is sealed by double-membrane vesicles to form autophagosome; a generalized mechanism for degradation of the organelle. Autophagic removal of damaged mitochondria is a conserved cellular process to maintain a healthy mitochondrion called Mitophagy. In plants and animals, mitophagy has crucial roles in stress responses, senescence, development, and programmed cell death. Mitophagy appears in mammals, fungi, and plants but many genes that controlled mitophagy are absent from plants. Numerous studies have been conducted by using ATG mutants for the identification of functional roles of Autophagy Related Genes (ATG) required during the autophagy process at various steps like; auto phagosome formation, ATG protein recruitment, etc. The role of more than 25 ATG genes in mitophagy has been discussed in this review paper. The main parameters, reviewed and summarized in this review paper, are the name of species, common name, function, domain, deletion, induction, and localization of these autophagy-related genes in the cell. This review will facilitate the students, researchers, and academics for their further research insights.

Research progress on function and mechanism of long non-coding RNA in glioma

Feipeng Tai, Xueming Zhao — Thu, 06 Jun 2024 00:00:00 +0200

This review aimed to comprehensively summarize the role of long non-coding RNA (lncRNA) in gliomas, the most common malignant tumors in the central nervous system, and explore their potential clinical applications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search using the PubMed database was conducted forty studies met the inclusion and exclusion criteria and were analyzed for type of intervention, the study’s design, participants’ demographics, and outcomes, including attrition. Gliomas, originating within the central nervous system, account for 40-45% of intracranial tumors. Despite advances in neurosurgical techniques, precise radiotherapy, and chemotherapy, the prognosis for glioma patients remains suboptimal. The review highlights the crucial regulatory role of lncRNA in gliomas. Differential expression of various lncRNAs, such as INHEG, SATB2-AS1, PSMB8-AS1, LINC01018, and SPRY4-IT1, has been observed in gliomas, suggesting their involvement in promoting or inhibiting tumorigenesis. Additionally, lncRNAs play roles in glioma characteristics such as proliferation, invasion, migration, angiogenesis, and the presence of glioma stem cells. The potential clinical applications of lncRNA in gliomas involve their association with tumor grading, diameter, metastasis, and family history. This review emphasizes the importance of understanding the molecular mechanisms involving lncRNA in gliomas. The identification of specific lncRNAs associated with gliomas provides potential molecular markers for diagnosis, differentiation, treatment, and prognosis evaluation. Further research is needed to uncover additional key lncRNAs and their underlying mechanisms, ultimately contributing to the improvement of glioma diagnosis and treatment.

Recent advances in immunotherapy in cancer treatment

Ayyub A. Patel Ayyub — Thu, 06 Jun 2024 00:00:00 +0200

Immunotherapy has emerged as a transformative approach in cancer treatment, leveraging the body’s own immune system to recognize and eradicate cancer cells. This review provides an overview of the recent advances and aspects in immunotherapy in cancer biology, from established therapies like checkpoint inhibitors and CAR-T cells to emerging innovative approaches and the challenges associated with their clinical translation.

The exploration includes an examination of checkpoint inhibitors, elucidating the mechanisms behind programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Recent clinical successes and ongoing trials demonstrate the efficacy of checkpoint inhibitors across diverse malignancies, underscoring the potential for durable responses and improved patient outcomes. CAR-T cell therapy represents a groundbreaking avenue in immunotherapy, involving the genetic modification of a patient's T cells to express chimeric antigen receptors (CARs) for targeted cancer cell recognition.

Furthermore, the review touches on the challenges associated with immunotherapy, including resistance mechanisms and adverse effects. Insightful discussions on overcoming resistance through combination therapies, adaptive treatment strategies, and emerging technologies underscore the ongoing efforts to enhance the long-term efficacy of immunotherapeutic interventions. In summary, this extensive review provides a comprehensive overview of recent advances in immunotherapy in cancer biology, highlighting the transformative impact of these therapies on patient outcomes, the challenges faced, and the promising directions for future research and clinical applications.

Exploring the nexus between sports performance and genetics: a comprehensive literature review

Sedat Kahya, Morteza Taheri — Thu, 06 Jun 2024 00:00:00 +0200

Sport is a multifactorial phenomenon that is influenced by many factors. Although many factors affect sports performance, genetic factors may be important issues that need to be examined. In addition, the relationship between sports performance and genes is still unclear. Due to the developments in omics technologies, approximately 185 genetic markers have been identified for the relationship between sports performance and genes. These genes are expressed differently in metabolism according to the characteristics of sports performance. The aim of this study was to investigate the relationship between sports and genetics. Pubmed, Pubmed Central and Google Scholar internet search engines were used in current study. Additionally, the PRISMA technique was used in the study design. For this purpose, COL1A1, COL5A1, ACTN3 and ELN genes may be important regulators on soft tissues. For endurance sports, genes like ACE, ACTN3, ADRB2, HFE, COL5A1, BDKRB2, NOS3, HIF, VEGF, AMPD and PPARGC1A significantly may influence performance limits. ACE and ACTN3 genes, on the other hand, may determine power/strength and speed skills in athletes. As a result, knowing the athlete's genetic predisposition to sports can be effective in achieving success.

Influence of antibiotics on the development of mitochondrial dysfunction

Thu, 06 Jun 2024 00:00:00 +0200

Antibiotics are an indispensable component of therapeutic strategies in the treatment of severe bacterial infections. Unfortunately, in addition to the emerging resistance of bacteria to antibiotics, side effects are an important problem with their use. Knowledge of the mechanisms underlying the development of side effects can make it possible to understand how it is possible to reduce their negative impact on the health of patients. One of the negative effects of antibiotics on the human organism is interference with homeostasis and the functioning of mitochondria. Side effects of antibiotics based on this influence require further study. Here we consider the mitochondria as a side target of antibiotics and the main strategies of antibiotics that cause mitochondrial dysfunction. Options are also considered on how to deal with this problem and even use it for good.

Revolutionizing medicine: Molecularly imprinted polymers as precision tools in cancer diagnosis and antibiotic detection

Thu, 06 Jun 2024 00:00:00 +0200

Molecularly imprinted polymers (MIPs) are pivotal in medicine, mimicking biological receptors with enhanced specificity and affinity. Comprising templates, functional monomers, and cross-linkers, MIPs form stable three-dimensional polymer networks. Synthetic templates like glycan and aptamers improve efficiency, guiding the molecular imprinting process. Cross-linking determines MIPs' morphology and mechanical stability, with printable hydrogels offering biocompatibility and customizable properties, mimicking native extracellular matrix (ECM) microenvironments. Their versatility finds applications in tissue engineering, soft robotics, regenerative medicine, and wastewater treatment. In cancer research, MIPs excel in both detection and therapy. MIP-based detection systems exhibit superior sensitivity and selectivity for cancer biomarkers. They target nucleic acids, proteins, and exosomes, providing stability, sensitivity, and adaptability. In therapy, MIPs offer solutions to challenges like multidrug resistance, excelling in drug delivery, photodynamic therapy, photothermal therapy, and biological activity regulation. In microbiology, MIPs serve as adsorbents in solid-phase extraction (SPE), efficiently separating and enriching antibiotics during sample preparation. They contribute to bacterial identification, selectively capturing specific strains or species. MIPs aid in detecting antibiotic residues using fluorescent nanostructures and developing sensors for sulfadiazine detection in food samples. In summary, MIPs play a pivotal role in advancing medical technologies with enhanced sensitivity, selectivity, and versatility. Applications range from biomarker detection to innovative cancer therapies, making MIPs indispensable for the accurate determination and monitoring of diverse biological and environmental samples.