Multidrug-resistant (MDR) Escherichia coli (E.coli) is a growing public health concern, largely driven by the overexpression of efflux pumps such as AcrAB-tolC. These efflux systems contribute to resistance against multiple antibiotic classes, including fluoroquinolones, β-lactams, and aminoglycosides. Despite the well-documented role of efflux pumps in resistance, inconsistencies in reported expression levels and regulatory mechanisms complicate the development of targeted therapies. This systematic review and meta-analysis aim to consolidate available evidence on acrAB-tolC expression patterns and evaluate the impact of efflux pump inhibitors (EPIs) on antibiotic susceptibility.

Magnaporthe oryzae is a fungus that infects monocotyledons such as rice, causing rice blast with reduced grain quality and hence is a significant challenge to food security. Although several fungicides are used, they are less effective and toxic with prolonged application. In this work on M. oryzae, we identified the protein targets that could be used for anti-fungal drug design based on meta-analysis of RNA-seq data retrieved from five experiments conducted on in planta M. oryzae isolated from infected rice at different time points ( < = 144 hpi). Through RNA-seq analysis, highly expressed genes (HEGs) were identified that were common across different experiments. WGCNA analysis further revealed clusters of co-expressed genes from which hub genes were identified which were also highly expressed. From the results of this study, genes such as MGG_05447, MGG_04732, and MGG_03619 were identified as potential targets for designing more effective fungicides. We selected MGG_04732 (chitinase) as a drug target and using virtual screening, molecular docking and molecular dynamics simulations, we identified emamectin as a potential antifungal agent that could act against it. The antifungal effectiveness of emamectin was further confirmed experimentally which showed it to have the ability to inhibit the growth of M. oryzae as demonstrated by the reduction in radial growth and melanin content. The results of this paper could be utilized for further field studies and applied in the design of new antifungals.

Arterial hypertension affects >1.28 billion adults globally, remaining a leading cause of cardiovascular morbidity and mortality. Despite effective therapies, suboptimal blood pressure control persists, highlighting the need for precision approaches. Epigenetic biomarkers, particularly DNA methylation (DNAm), have emerged as potential tools to enhance risk stratification and personalize antihypertensive therapy, yet their clinical relevance remains uncertain. To systematically synthesize evidence on genetic and epigenetic biomarkers associated with hypertension, focusing on DNAm signatures, regulatory pathways, and translational potential, we conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, registered in PROSPERO (Chronic Renal Disease (CRD) 420251059256). PubMed, MEDLINE, Embase, and ScienceDirect were searched up to March 2025. Eligible studies investigated genetic or epigenetic markers, such as DNAm, single nucleotide polymorphisms, or chromatin modifications in adult hypertension populations. Data on study design, populations, biomarkers, analytical methods, and outcomes were extracted. Risk of bias was assessed using RoB 2 and Risk of Bias in Nonrandomized Studies of Interventions tool. Twelve studies were included, encompassing cross-sectional and longitudinal designs. DNAm signatures at loci including AGTR1, PHGDH, SLC7A11, Angiotensin-Converting Enzyme (ACE), and WNT3A were recurrently associated with blood pressure regulation. Transancestry genome-wide analyses identified methylation-enriched loci such as KCNK3, PDE3A, and PRDM6. However, no study demonstrated predictive value for clinical end points or robust replication across diverse populations. Methodological heterogeneity limited longitudinal data and underrepresentation of low- and middle-income countries were key limitations. Although epigenetic markers show promise for hypertension research, current evidence remains exploratory. Rigorous, longitudinal studies integrating clinical end points are essential for advancing toward clinical translation.

Alzheimer's disease (AD) poses a major challenge due to its impact on the elderly population and the lack of effective early diagnosis and treatment options. In an effort to address this issue, a study focused on identifying potential biomarkers and therapeutic agents for AD was carried out. Using RNA-Seq data from AD patients and healthy individuals, 12 differentially expressed genes (DEGs) were identified, with 9 expressing upregulation (ISG15, HRNR, MTATP8P1, MTCO3P12, DTHD1, DCX, ST8SIA2, NNAT, and PCDH11Y) and 3 expressing downregulation (LTF, XIST, and TTR). Among them, TTR exhibited the lowest gene expression profile. Interestingly, functional analysis tied TTR to amyloid fiber formation and neutrophil degranulation through enrichment analysis. These findings suggested the potential of TTR as a diagnostic biomarker for AD. Additionally, druggability analysis revealed that the FDA-approved drug Levothyroxine might be effective against the Transthyretin protein encoded by the TTR gene. Molecular docking and dynamics simulation studies of Levothyroxine and Transthyretin suggested that this drug could be repurposed to treat AD. However, additional studies using in vitro and in vivo models are necessary before these findings can be applied in clinical applications.

Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes.

Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC.

Small interfering RNA (siRNA) holds promise as a therapeutic approach for various diseases, yet challenges persist in achieving efficient delivery, biodistribution, and minimizing off-target effects. Lipidic nanoformulations are being developed to address these hurdles, but the optimal dose for preclinical investigations remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of nanoformulated siRNA and explore factors influencing dose and biodistribution, informing future research in this field. A comprehensive search across four electronic databases identified 25 potential studies, with 15 selected for meta-analysis after screening. Quality assessment was conducted using SYRCLE's risk of bias tool modified for animal studies based on research question. Study found an average siRNA dose of 1.513 ± 0.377 mg/kg with mean downregulation of 65.79 % achieved, with siRNA-LNPs mainly accumulating in the liver. While individual factors showed no significant correlation, a positive association between dose and downregulation was observed, alongside other influencing factors. Extrapolating intravenous doses to potential oral doses, we suggest an initial oral dose range of 1.5 to 8 mg/kg, considering siRNA-LNPs bioavailability. These findings contribute to advancing RNA interference research and encourage further exploration of siRNA-based treatments in personalized medicine.

Exposure to pesticides is a risk factor for various diseases, yet its association with biological aging remains unclear. We aimed to systematically investigate the relationship between pesticide exposure and biological aging.

Several studies show that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in human cancer, which was associated with several clinical features and may have the potential to be prognostic markers. However, the significance of HOTAIR in hepatocellular carcinoma remains unclear. We performed a meta-analysis and bioanalysis to further investigate the association between HOTAIR and hepatocellular carcinoma.

Glycans have attracted much attention in cancer therapeutic strategies, and cell surface proteins and lipids with glycans are known to be altered during the carcinogenic process. However, our understanding of how the glycogenes profile responds to drug stimulation remains incomplete. In this study, we search public databases for Sequence Read Archive data on drug-treated liver cancer cells, with the aim to comprehensively analyze the drug responses of glycogenes via bioinformatic meta-analysis. The study comprised 86 datasets, encompassing eight distinct liver cancer cell lines and 13 different drugs. Differentially expressed genes were quantified, and 399 glycogenes were identified. The glycogenes signature was then analyzed using bioinformatics methodologies. In the Protein-protein interaction network analysis, we identified drug-responsive glycogenes such as Beta-1,4-Galactosyltransferase 1, GDP-Mannose 4,6-Dehydratase, UDP-Glucose Ceramide Glucosyltransferase, and Solute Carrier Family 2 Member 4 as key glycan biomarkers. In the enrichment analysis using the pathway list of glycogenes, the results also demonstrated that drug stimulation resulted in alterations to glycopathway-related genes involved in several processes, namely O-Mannosylation, POMGNT2 Type, Capping, Heparan Sulfate Sulfation, and Glucuronidation pathways. These genes and pathways commonly exhibit variable expression across multiple liver cancer cells in response to the same drug, making them potential targets for new cancer therapies. In addition to their primary roles, drugs may also participate in the regulation of glycans. The insights from this study could pave the way for the development of liver cancer therapies that target the regulation of gene profiles involved in the biosynthesis of glycans.

Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21. Associations of human infant DNA methylation in homologous mouse genes with prenatal DEHP or Pb were examined with a meta-analysis. Differential methylation was observed on 6 cytosines (adjusted-p < 0.05) and 90 regions (adjusted-p < 0.001). This translational approach offers a unique method that can detect conserved epigenetic differences that are developmentally susceptible to environmental toxicants.

Estrogen receptor (ER) is a molecular marker and target for diagnosing and treating breast cancer (BC). ER-α36, a novel estrogen receptor subtype, involved in the proliferation, differentiation, metastasis, and invasion of tumor cells. It is closely linked to the progression of various cancers. Therefore, studying ER is of high significance in treating BC. In this study, we will investigate the changes in the expression level of ER-α36 in patients with BC treated by chemotherapy through meta-analysis, so as to evaluate the clinical value of ER-α36 in the prognosis of BC treated by chemotherapy. English databases such as PubMed, Web of Science, Embase, and The Cochrane Library were searched to retrieve the articles published from the establishment of the database to April 2023. The keywords included chemotherapy, neoadjuvant chemotherapy, breast cancer, estrogen receptor alpha, and ER-α36. Five suitable studies, encompassing 636 patients, were ultimately selected. The meta-analysis results revealed that, following the chemotherapy, the analysis of ER-α36 positive cases yielded an Odds Ratio (OR) of 0.42, a 95% confidence interval (CI) of 0.28-0.64 (Z = 4.00, P < 0.0001). Additionally, the analysis of cases exhibiting remission in BC demonstrated an OR of 2.22 (95% CI = 1.40-3.50, Z = 3.40, P = 0.0007). Compared to patients receiving single chemotherapy agents or those untreated with chemotherapy, the combined use of multiple chemotherapy drugs can significantly reduce the levels of ER-α36 in BC patients, enhancing the remission rate of BC. ER-α36 can serve as a critical indicator for assessing the prognosis of BC following chemotherapy.

Chilling injury is one of the most significant limitations for low temperature storage of postharvest fruits and vegetables, causing quality deterioration and economic loss. Increasing studies indicated that methyl jasmonate (MeJA) is critical in regulating the postharvest fruit and vegetables chilling tolerance. Based on a meta-analysis, the review analyzed the action of exogenous MeJA application on the chilling index in postharvest fruit and vegetables and summarized MeJA's mechanisms for controlling postharvest chilling injury. The meta-analysis found that MeJA treatment remarkably inhibited postharvest fruit and vegetable chilling injury. Moreover, we concluded the following function mechanism of MeJA on postharvest fruit and vegetable chilling tolerance: (1) Enhancing membrane integrity and energy supply, (2) Increasing antioxidant activity, (3) Enhancing arginine pathway, (4) Enhancing sugar metabolism, (5) Regulating phenolic metabolism, (6) Activating CBF pathway, (7) Regulating HSP accumulation and expression, and (8) Crosstalk with phytohormone. Finally, we summarized the regulatory mechanisms of MeJA on postharvest fruit and vegetable biological processes at the transcriptional and post-translational levels.

This meta-analysis examined the prognostic role of brain and acute leukemia, cytoplasmic (BAALC), Ecotropic virus integration site-1 (EVI1) and Wilms' tumor 1 (WT1) genes at different time-points during conventional chemotherapy.

Predicting cancer cells' response to a plant-derived agent is critical for the drug discovery process. Recently transcriptomes advancements have provided an opportunity to identify regulatory signatures to predict drug activity. Here in this study, a combination of meta-analysis and machine learning models have been used to determine regulatory signatures focusing on differentially expressed transcription factors (TFs) of herbal components on cancer cells. In order to increase the size of the dataset, six datasets were combined in a meta-analysis from studies that had evaluated the gene expression in cancer cell lines before and after herbal extract treatments. Then, categorical feature analysis based on the machine learning methods was applied to examine transcription factors in order to find the best signature/pattern capable of discriminating between control and treated groups. It was found that this integrative approach could recognize the combination of TFs as predictive biomarkers. It was observed that the random forest (RF) model produced the best combination rules, including AIP/TFE3/VGLL4/ID1 and AIP/ZNF7/DXO with the highest modulating capacity. As the RF algorithm combines the output of many trees to set up an ultimate model, its predictive rules are more accurate and reproducible than other trees. The discovered regulatory signature suggests an effective procedure to figure out the efficacy of investigational herbal compounds on particular cells in the drug discovery process.

Previously, we have reported that the dysregulation of ketogenesis plays an important role in the carcinogenesis of clear cell renal cell carcinoma (ccRCC). Here, we demonstrate decreased expression of the HMGCS2 gene in ccRCC, a critical enzyme for the synthesis of the ketone body β-hydroxybutyrate (β-OHB). We found that the reduced transcription of the HMGCS2 gene in ccRCC cells was significantly correlated to a higher relative methylation rate in its promotor region. The higher methylation rate in the region of the transcription start site and 1st exon of the HMGCS2 gene was, in turn, correlated with a worse clinical outcome for patients. The transcription of HMGCS2 was possible to restore by treatment with 5-aza-2'-deoxycytidine and with the histone deacetylase inhibitor β-OHB. Therefore, the low levels of the HMGCS2 enzyme in ccRCC may be the consequence of hypermethylation of the HMGCS2 promotor. The ensuing reduction in the ketone body levels further suppresses the transcription of HMGCS2 via a feedback loop. Ectopic expression of HMGCS2 attenuates the migration and invasion of ccRCC but does not affect the proliferative capacity of ccRCC cells in vitro. In addition, we showed that ectopic expression of HMGCS2 boosts the intracellular levels of β-OHB and that exogenously applied β-OHB suppresses the motility and invasion of ccRCC. Our study reveals crosstalk between genes that regulate metabolism and their metabolites, thus providing a better understanding of the epigenetic mechanism involved in ccRCC carcinogenesis and suggesting opportunities for metabolic therapy of tumors. Initially, we suggest that the mRNA level of HMGCS2 could serve as a potentially valuable diagnostic (AUC = 0.918, p < 0.001) and prognostic biomarker.

Esophageal cancer, as a high incidence of gastrointestinal cancer, has an indelible impact on human life and health. The combination of Chinese herbal injections and chemotherapy is commonly applied in the treatment of Esophageal cancer.

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing.

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

Despite the advancements in primary brain tumour diagnoses and treatments, the mortality rate remains high, particularly in glioblastoma (GBM). Chemoresistance, predominantly in recurrent cases, results in decreased mean survival of patients with GBM. We aimed to determine the chemosensitisation and oncogenic characteristics of zinc finger protein 36-like 2 (ZFP36L2) in LN18 GBM cells via RNA interference (RNAi) delivery. We conducted a meta-analysis of microarray datasets and RNAi screening using pooled small interference RNA (siRNA) to identify the druggable genes responsive to GBM chemosensitivity. Temozolomide-resistant LN18 cells were used to evaluate the effects of gene silencing on chemosensitisation to the sub-lethal dose (1/10 of the median inhibitory concentration [IC50]) of temozolomide. ZFP36L2 protein expression was detected by western blotting. Cell viability, proliferation, cell cycle and apoptosis assays were carried out using commercial kits. A human apoptosis array kit was used to determine the apoptosis pathway underlying chemosensitisation by siRNA against ZFP36L2 (siZFP36L2). Statistical analyses were performed using one-way analysis of variance; p > 0.05 was considered significant. The meta-analysis and RNAi screening identified ZFP36L2 as a potential marker of GBM. ZFP36L2 knockdown significantly induced apoptosis (p < 0.05). Moreover, ZFP36L2 inhibition led to increased cell cycle arrest and decreased cell proliferation. Downstream analysis showed that the sub-lethal dose of temozolomide and siZFP26L2 caused major upregulation of BCL2-associated X, apoptosis regulator (BAX). ZFP36L2 has oncogenic and chemosensitive characteristics and may play an important role in gliomagenesis through cell proliferation, cell cycle arrest and apoptosis. This suggests that RNAi combined with chemotherapy treatment such as temozolomide may be a potential GBM therapeutic intervention in the future.