Biochemical Genetics[JOURNAL]
Sun
200 papers
FTO Deficiency Inhibits Vascular Endothelial Cell Apoptosis and Improved Mitophagy in Obesity-Related Hypertension by Enhancing NDRG1 m6A Methylation.
Gan Q, Yang N
Biochem Genet · 2026 Jun · PMID 42240709 · Publisher ↗
Vascular endothelial dysfunction contributes to obesity-related hypertension, yet its mechanisms remain unclear. This study examined the role of N6-methyladenosine (m6A) in this process using in vivo and in vitro models....
Vascular endothelial dysfunction contributes to obesity-related hypertension, yet its mechanisms remain unclear. This study examined the role of N6-methyladenosine (m6A) in this process using in vivo and in vitro models. C57BL/6J mice fed a high-fat diet (HFD) developed obesity-related hypertension, while oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs) simulated endothelial injury. Global m6A levels were assessed via dot blot, and m6A regulators were quantified by qPCR. Endothelial function was evaluated through viability (CCK-8), apoptosis (flow cytometry), and mitophagy (Western blot and immunofluorescence staining). Mechanistic studies included methylated RNA immunoprecipitation (MeRIP) and dual-luciferase assays. Results showed HFD reduced m6A levels but elevated Fto expression in mice, while ox-LDL decreased m6A levels and upregulated FTO in HAECs. FTO knockdown in HAECs enhanced viability and mitophagy while suppressing apoptosis under ox-LDL stress. Mechanistically, FTO silencing increased m6A methylation on NDRG1 mRNA, leading to its degradation via YTHDF2 recognition. NDRG1 overexpression reversed these effects, restoring apoptosis while reducing mitophagy and viability. These findings reveal that FTO depletion attenuates endothelial dysfunction in obesity-related hypertension by enhancing m6A-mediated suppression of NDRG1, highlighting the FTO/m6A/NDRG1/YTHDF2 axis as a therapeutic target for vascular protection.
Circular RNA hsa_circ_0002473 Boosts Gastric Cancer Progression via the miR-873-5p/TEAD1 Axis.
Wang M, Wu Z, Tong R … +4 more , Geng Y, Li F, Huo X, Yu L
Biochem Genet · 2026 Jun · PMID 42240708 · Publisher ↗
Circular RNAs (circRNAs) display cancer-specific expression profiles associated with the prevalence and fatality rates of gastric cancer (GC). Although the functions of certain circRNAs in GC advancement have been clarif...
Circular RNAs (circRNAs) display cancer-specific expression profiles associated with the prevalence and fatality rates of gastric cancer (GC). Although the functions of certain circRNAs in GC advancement have been clarified, a recently identified circRNA hsa_circ_0002473, require further examination. The current study reveals that hsa_circ_0002473 facilitates gastric cancer progression. Initially, we observed that hsa_circ_0002473 exhibited high expression levels in gastric cancer tissue and cells. Subsequent investigations utilizing the Incucyte S3 imaging system, colony formation assay, scratch wound healing assay, and mouse xenograft models demonstrated that knockdown of hsa_circ_0002473 significantly inhibited the proliferation and migration of GC cells. Additionally, dual-luciferase assays confirmed hsa_circ_0002473 directly binds miR-873-5p and miR-873-5p targeting of the TEAD1 3'UTR. Crucially, rescue experiments demonstrated that miR-873-5p restoration or TEAD1 knockdown reduced hsa_circ_0002473-driven GC cells proliferation and migration. Our findings demonstrate that hsa_circ_0002473 elevates TEAD1 expression by competitively sequestering miR-873-5p, thereby promoting gastric cancer progression. This newly identified circRNA regulatory axis could enrich the genetic characteristics of GC, provide a possible medicinal genetic target for GC, and present a new perspective for GC molecular diagnosis.
Association of miR-146a/b and miR-181a with Chronic Obstructive Pulmonary Disease.
Abbaspour-Aghdam S, Valizadeh A, Pouya K … +6 more , Jafarzadeh S, Mikaeili H, Nadiri M, Hajiasgharzadeh K, Ahmadi M, Sadeghi A
Biochem Genet · 2026 Jun · PMID 42240707 · Publisher ↗
miRNAs play critical roles in regulating inflammatory responses in chronic obstructive pulmonary disease (COPD). This study investigated the expression patterns of miR-146a/b and miR-181a, along with associated inflammat...
miRNAs play critical roles in regulating inflammatory responses in chronic obstructive pulmonary disease (COPD). This study investigated the expression patterns of miR-146a/b and miR-181a, along with associated inflammatory mediators, in COPD patients. This cross-sectional study included 40 patients with acute exacerbation of COPD (AECOPD), 40 patients with stable COPD, and 40 healthy controls. Expression levels of miR-146a, miR-146b, and miR-181a in peripheral blood mononuclear cells (PBMCs) were quantified using quantitative real-time PCR. Serum concentrations of high-mobility group box 1 (HMGB1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were measured by ELISA. Cytokine mRNA expression was assessed in PMA-stimulated PBMCs. Multivariable logistic regression was performed to adjust for potential confounders including age and smoking pack-years. Expression of miR-146a, miR-146b, and miR-181a was significantly decreased in both COPD and AECOPD groups compared to controls (all p < 0.001), with further reduction in AECOPD patients. Multivariable analysis demonstrated that decreased miR-146a (OR = 2.45, 95% CI: 1.58-3.81, p < 0.001) and miR-181a (OR = 2.18, 95% CI: 1.42-3.35, p < 0.001) remained independent predictors of COPD after adjusting for age and smoking exposure. Serum HMGB1, IL-6, and TNF-α levels were significantly elevated in COPD patients, while IL-10 showed decreased expression. PMA-stimulated PBMCs from COPD patients demonstrated enhanced pro-inflammatory cytokine production capacity. In exploratory ROC analysis, miR-146a showed moderate discriminatory capacity (AUC = 0.78, 95% CI: 0.65-0.91). Dysregulation of miR-146a/b and miR-181a is independently associated with COPD, even after accounting for smoking exposure. These findings suggest potential roles in disease pathophysiology, though prospective validation in larger, independent cohorts is required before clinical applicability can be determined.
ANGPTL1 Inhibits the Growth, Migration, and Angiogenesis of Gastric Cancer Cells by Downregulating VEGFA Expression.
Jin L, Lu G, Shang R … +3 more , Hu J, Zhu C, Yan T
Biochem Genet · 2026 Jun · PMID 42225858 · Publisher ↗
Gastric cancer (GC) remains one of the most common malignant tumors worldwide, with high incidence and mortality rates. Angiopoietin-like protein 1 (ANGPTL1), a member of the ANGPTL family, is known to function as an ant...
Gastric cancer (GC) remains one of the most common malignant tumors worldwide, with high incidence and mortality rates. Angiopoietin-like protein 1 (ANGPTL1), a member of the ANGPTL family, is known to function as an anti-angiogenic factor and tumor suppressor. However, its role and underlying mechanisms in GC development have not been investigated and require further investigation. Protein expression levels were analyzed using western blotting and immunofluorescence (IF) assays. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated through colony formation assays. Cell migration and invasion were examined using Transwell assays. Angiogenic capacity was determined through tube formation assays. The VEGFA mRNA expression was detected through RT-qPCR. The level of VEGFA was confirmed through ELISA. The tumor size, volume and weight were confirmed through the in vivo assay. The CD31 protein expression was verified though IHC assay. ANGPTL1 was found to be expressed at lower levels in GC cells, and negatively correlated with VEGFA. ANGPTL1 significantly inhibited GC cell proliferation, migration, and invasion. Furthermore, ANGPTL1 suppressed angiogenesis in vitro. Mechanistically, it was observed that ANGPTL1 overexpression reduced VEGFA expression, and ANGPTL1 can interact with VEGFA. Importantly, reintroduction of VEGFA reversed the inhibitory effects of ANGPTL1 on GC progression. Lastly, VEGFA overexpression retarded the tumor growth in vivo. This study demonstrates that ANGPTL1 inhibits the growth, migration, and angiogenesis of GC cells by downregulating VEGFA expression. These findings suggest that ANGPTL1 may serve as a promising therapeutic target for gastric cancer treatment.
LncRNA CCAT1/miR-490-3p/VDAC1 Axis Promotes Colorectal Cancer Progression by Activating Glycolysis.
Ge Y, Liu Q, Zhao L … +2 more , Mi W, Qi X
Biochem Genet · 2026 Jun · PMID 42223552 · Publisher ↗
To elucidate the molecular mechanism by which long non-coding RNA CCAT1 (LncRNA CCAT1) promotes colorectal cancer (CRC) progression via regulation of microRNA miR-490-3p and Voltage-Dependent Anion Channel 1 (VDAC1), the...
To elucidate the molecular mechanism by which long non-coding RNA CCAT1 (LncRNA CCAT1) promotes colorectal cancer (CRC) progression via regulation of microRNA miR-490-3p and Voltage-Dependent Anion Channel 1 (VDAC1), thereby activating glycolysis. In vitro, LncRNA CCAT1, miR-490-3p, and VDAC1 expression in CRC cell lines (HT-29, SW620, SW480, HCT116) and normal colonic epithelial cells (NCM460) was quantified by qRT-PCR. Selected lines underwent CCAT1, miR-490-3p, or VDAC1 overexpression/knockdown. Dual-luciferase assays confirmed interactions between CCAT1 and miR-490-3p, and between miR-490-3p and VDAC1. Cell proliferation was assessed by CCK-8 and colony formation assays; glucose consumption, ATP production, and lactate secretion were measured by ELISA. In vivo, nude mice received subcutaneous xenografts of modified HT-29 cells. Tumor growth, body weight, histopathology, apoptosis, glycolysis-related gene/protein expression (VDAC1, Hexokinase 2 [HK2], Pyruvate Kinase M2 [PKM2], Glucose Transporter 2 [GLUT2]), and glucose metabolism were evaluated. CCAT1 was significantly upregulated in CRC cells. Its knockdown suppressed proliferation and glycolysis, whereas overexpression had the opposite effect. CCAT1 acted as a competing endogenous RNA for miR-490-3p, alleviating miR-490-3p-mediated repression of VDAC1, leading to VDAC1 upregulation. Overexpressing miR-490-3p or silencing VDAC1 inhibited CRC cell proliferation and glycolysis. In vivo, CCAT1 or VDAC1 knockdown reduced tumor growth and altered glycolysis-related gene/protein expression. LncRNA CCAT1 promotes CRC progression by sponging miR-490-3p to upregulate VDAC1, thereby activating glycolysis. The CCAT1/miR-490-3p/VDAC1 axis may serve as a promising diagnostic and therapeutic target in CRC.
MiR-146b-5p/ERBB4 Axis Drives LPS-induced Acute Kidney Injury by Modulating NF-κB/p65.
Sun D, Wang L, Liu S
Biochem Genet · 2026 May · PMID 42207454 · Publisher ↗
We aimed to explore the role of miR-146b-5p in lipopolysaccharide (LPS)-induced acute kidney injury. C57BL/6N mice were intraperitoneally injected with LPS to establish an acute kidney injury model, and the effects of mi...
We aimed to explore the role of miR-146b-5p in lipopolysaccharide (LPS)-induced acute kidney injury. C57BL/6N mice were intraperitoneally injected with LPS to establish an acute kidney injury model, and the effects of miR-146b-5p inhibition on AKI progression in vivo were explored. The renal function of mice was evaluated by determining serum creatinine and blood urea nitrogen levels. Kidney histopathology was examined using H&E and PAS staining. Cell apoptosis in vivo was analyzed via TUNEL staining, and the TUNEL-positive cells per field were quantified. HK-2 cells were stimulated with LPS (1 µg/mL) to replicate an inflammatory AKI environment in vitro. To investigate function and molecular mechanisms of miR-146b-5p, HK-2 cells were transfected with mimics and inhibitor of miR-146b-5p. Apoptosis in HK-2 cells was assessed via flow cytometry using Annexin-V/FITC and propidium iodide (PI) staining, while levels of inflammatory cytokine (IL-1β, IL-6, TNF-α) were measured using ELISA. RNA pull-down and luciferase assays were used to explore interaction between miR-146b-5p and ERBB4 and activation of the downstream NF-κB/p65 signaling was investigated via western blot. The results showed that miR-146b-5p expression was upregulated by ~ 133% in the LPS-induced AKI mouse model (p < 0.01) and increased up to ~ 137% in LPS-treated HK-2 cells (p < 0.001) compared to control. Inhibition of miR-146b-5p improved renal function, and BUN levels were reduced by ~ 48% (p < 0.01) and creatinine levels were decreased by ~ 40% compared to LPS + NC antagomir group (p < 0.01). Inhibition of miR-146b-5p also attenuated tissue injury, suppressed cell apoptosis, with the TUNEL-positive cells reduced by 46% compared to LPS + NC antagomir group (p < 0.01), and lowered inflammatory cytokine levels, with IL-1β reduced by ~ 54% (p < 0.01), IL-6 reduced by ~ 55% (p < 0.01), and TNF-α reduced by 51% (p < 0.01) compared to LPS + NC antagomir group. Mechanistically, miR-146b-5p directly targeted ERBB4, whose suppression reversed the protective effects of miR-146b-5p inhibition. Importantly, we found that the miR-146b-5p/ERBB4 axis regulates the NF-κB/p65 signaling pathway, providing a potential mechanistic link between miRNA activity and inflammation in AKI. In conclusion, this study reveals that the miR-146b-5p/ERBB4 axis promotes the activation of the NF-κB pathway and drives apoptosis and inflammation in LPS-induced AKI, suggesting miR-146b-5p as a novel therapeutic target for AKI.
The Role of Small Segmental Duplications in Generating Identical Isoforms Through Alternative Splicing Sites.
Huseynova Mustafayeva U, Babayeva S, Mustafayev O … +3 more , Hasanli L, Goldenkova-Pavlova I, Mammadova A
Biochem Genet · 2026 May · PMID 42207453 · Publisher ↗
Alternative splicing plays a crucial role in expanding proteomic diversity but can also generate identical isoforms under certain conditions. While mutually exclusive splicing of tandem exons has occasionally been report...
Alternative splicing plays a crucial role in expanding proteomic diversity but can also generate identical isoforms under certain conditions. While mutually exclusive splicing of tandem exons has occasionally been reported to produce identical isoforms, the extent to which other splicing events contribute to this phenomenon remains unclear. In this study, we demonstrate that alternative 5' and 3' splice site selection can also lead to the formation of identical isoforms, providing an additional type of splicing event for functional redundancy in transcriptomes. To address this, we analyzed reference genome annotations from 15 plant species, including Arabidopsis thaliana and wheat (Triticum aestivum), obtained from the RefSeq database. Identical isoforms were computationally defined as transcripts with distinct exon-intron structures but identical coding sequences. Our analysis reveals that the majority of alternative 5' and 3' fragments originate from small segmental duplications, suggesting that sequence repetition within gene regions facilitates the emergence of such splicing patterns. We also observed differences in the annotated 5' UTRs of some identical isoforms. However, since the alternative splicing sites themselves were not located within UTRs, these differences may reflect annotation uncertainty rather than genuine AS-derived variation. Given that UTR predictions in reference databases are not always precise, such observations should be interpreted cautiously. Expression analysis using an isoform-specific k-mer approach confirmed that identical isoforms can be differentially regulated. These findings suggest that, beyond expanding protein diversity, alternative splicing can also generate redundant isoforms that are differentially expressed at the RNA level, indicating potential regulatory roles. By elucidating the structural and regulatory factors contributing to the formation and retention of identical isoforms, our study provides new insights into the evolutionary and functional significance of alternative splicing in plants.
Bacillus spp. Mediated Growth Enhancement and Antioxidative Defence Activation in Peppermint (Mentha piperita L.).
Singh V, Chandra S, Kishor R … +5 more , Maurya N, Luqman S, Verma RK, Yadav AK, Kumar B
Biochem Genet · 2026 May · PMID 42207452 · Publisher ↗
Peppermint (Mentha piperita L.) is a valuable medicinal and aromatic herb cultivated globally for its essential oil, prized for its therapeutic and flavouring properties. The productivity and essential oil quality of pep...
Peppermint (Mentha piperita L.) is a valuable medicinal and aromatic herb cultivated globally for its essential oil, prized for its therapeutic and flavouring properties. The productivity and essential oil quality of peppermint is strongly influenced by the intervention of biotic and abiotic elicitors, which eventually induces plant growth dynamics, redox homeostasis, and secondary metabolite biosynthesis. This study evaluates the effect of five plant growth promoting rhizobacteria (PGPRs): Bacillus tequilensis (T1), Bacillus subtilis (T2), Bacterium strain (T3), Bacillus thuringiensis (T4), and Bacillus cereus (T5), to access the modulation efficiency of these plant probionts over morphological, physiological, and biochemical parameters of peppermint variety CIM-Suras. The surface sterilized, uniform sized suckers of a menthol-rich peppermint variety CIM-Suras were inoculated with five aforementioned Bacillus spp., endowed with phosphate solubilization, ammonia production, siderophore production, and Indole Acetic Acid production efficiencies, in triplicate. The results of the study revealed that T2 (Bacillus subtilis) has significantly enhanced the photosynthetic process, contents of chlorophyll (64.71%), accumulation of proline (43.17%), SOD (24.89%), and catalase (56.33%), over the control, followed by T1 (Bacillus tequilensis), and T4 (Bacillus thuringiensis). Treatment with Bacillus subtilis (T2) showing maximum improvement in studied morphological, physiological and biochemical parameters in peppermint suggests the potential of the isolate to abate the oxidative damage of the cells during altering environmental conditions. These findings underscore the efficiency of peppermint-native Bacillus-based PGPRs, especially B. subtilis, for improving crop growth, stress resilience, and essential oil yield in a menthol-rich cultivar. This approach offers a sustainable alternative to synthetic fertilizers to improve peppermint productivity.
A User-Friendly Protocol for Microinjection into Teleost Embryos to Study Gene Function.
Mendoza A, Simon I, Hasan S
Biochem Genet · 2026 May · PMID 42189436 · Publisher ↗
Zebrafish (Danio rerio) and medaka (Oryzias latipes) are popular teleost models used in developmental biology and functional genomics. To achieve high-quality and reproducible microinjections, it is essential to have rob...
Zebrafish (Danio rerio) and medaka (Oryzias latipes) are popular teleost models used in developmental biology and functional genomics. To achieve high-quality and reproducible microinjections, it is essential to have robust protocols for breeding, egg collection, and the precise delivery of genetic material. In this protocol, we present a comprehensive and optimized methodology for setting up breeding tanks under controlled photoperiod conditions to maximize egg yield while minimizing contamination. We provide detailed procedures for sex identification, pair selection, the use of grated breeding inserts, and methods to increase egg collection efficiency. We outline procedures for making injection gel beds, pulling needles, and calibration using one-microliter microcapillaries to achieve consistent nanoliter-scale injections. Our protocol outlines settings for the pico-liter injector that are optimized to deliver a precise amount per pulse with minimal variability. Finally, we demonstrate the application of these methods for gene knockdown using morpholino antisense oligonucleotides, gene knockout using CRISPR-Cas9, and gain-of-function mRNA overexpression experiments. Phenotypic assessments conducted at various developmental stages to evaluate gene-specific effects reveal consistent phenotypic outcomes between the morpholino and CRISPR-Cas9 approaches. This easy and comprehensive protocol enables efficient, precise, and scalable genetic manipulation of zebrafish and medaka embryos, thereby supporting advanced functional studies in developmental biology and disease modeling. To our knowledge, this is the first unified protocol for both zebrafish and medaka microinjection systems achieving 97.7% phenotype penetrance in CRISPR-Cas9 knockouts with precision together with a triple validation approach that confirms gene function across multiple techniques.
Genetic Diversity of BK Polyomavirus Among Renal Transplant Recipients in Yunnan, China.
Pu D, Pan Y, Ming L … +6 more , Jie G, Jiang K, Bai M, Xu X, Xu H, Yin L
Biochem Genet · 2026 May · PMID 42171950 · Publisher ↗
BK polyomavirus (BKV) infection, a common complication following kidney transplantation, can lead to BKV-associated nephropathy (BKVN). Molecular genetic studies have classified BKV into four genotypes (I-IV); however, c...
BK polyomavirus (BKV) infection, a common complication following kidney transplantation, can lead to BKV-associated nephropathy (BKVN). Molecular genetic studies have classified BKV into four genotypes (I-IV); however, comprehensive molecular characterization of BKV strains circulating in China remains limited. This study aimed to elucidate the predominant subtypes and clinical infection characteristics of BKV strains among kidney transplant recipients in Yunnan, a province in southwestern China. PCR-amplified BKV DNA sequences from kidney transplant recipients were aligned with reference strains and subjected to phylogenetic analysis. The viral VP1 gene was successfully amplified from 180 participants, spanning 16 ethnic groups. Genotype I was the predominant viral strain (56.66%, 102/180), followed by genotype IV (43.33%, 78/180), while genotypes II and III were not detected. Among genotypic subtypes, IVc-1 was most prevalent (40.0%, 72/180), followed by Ic (38.3%, 69/180) and Ib-1 (18.3%, 33/180). IVa-1 and IVa-2 were rare, identified in only 0.6% (n = 1) and 2.2% (n = 4) of cases, respectively. No significant differences in sex, age, BKVN incidence, BK viremia, or viruria were observed between patients with BKV-I and BKV-IV infections. Among the five confirmed BKVN cases, two were genotyped as subtype Ic, one as Ib-1, and two as IVc-1. Clinical phenotypes were also comparable between patients with BKV-I and BKV-IV infections. This study represents the largest single-center sequencing analysis of BKV in kidney transplant recipients in China, offering a valuable genomic resource for future research.
The LINC00920/miR-6834-3p/CPN1 Axis Modulates Immune Dysregulation in Sepsis-Associated Acute Kidney Injury and Serves as a Diagnostic Biomarker.
Wang Y, Zhang J, Liu K … +2 more , Shen Q, Zhang Y
Biochem Genet · 2026 May · PMID 42159854 · Publisher ↗
Sepsis-associated acute kidney injury (SA-AKI) is a serious complication with high mortality and lacks effective diagnostic and treatment strategies. This study aims to investigate the role of the LINC00920/miR-6834-3p/C...
Sepsis-associated acute kidney injury (SA-AKI) is a serious complication with high mortality and lacks effective diagnostic and treatment strategies. This study aims to investigate the role of the LINC00920/miR-6834-3p/CPN1 axis in SA-AKI and evaluate its diagnostic value. Clinical serum samples and in vitro cell models were used to explore the role of the LINC00920/miR-6834-3p/CPN1 axis in SA-AKI. Serum expression of LINC00920, miR-6834-3p and CPN1 was detected to analyze their expression patterns in SA-AKI, and their diagnostic value was evaluated to verify potential biomarker utility. Dual-luciferase reporter assay, mutant construct and rescue experiments were performed to confirm the regulatory relationship of the LINC00920/miR-6834-3p/CPN1 axis. Functional experiments were conducted to detect cell injury, macrophage polarization and NET formation, so as to clarify the biological function of the axis in SA-AKI progression. Clinical analysis showed LINC00920 and CPN1 were downregulated, miR-6834-3p upregulated in SA-AKI. LINC00920 was negatively correlated with SA-AKI severity, suggesting its association with disease progression. The LINC00920/miR-6834-3p/CPN1 panel had high diagnostic value for SA-AKI and severity (AUC = 0.913, 0.912). In vitro experiments confirmed LINC00920 acts as a ceRNA to sponge miR-6834-3p and upregulate CPN1, exerting a protective role in SA-AKI by alleviating cell injury, M1 polarization and NET formation. The LINC00920/miR-6834-3p/CPN1 axis regulates SA-AKI progression, correlates with disease severity, and is a promising diagnostic biomarker.
Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses.
Xie Z, Ma H, Liu Y … +1 more , Lai W
Biochem Genet · 2026 May · PMID 42159853 · Publisher ↗
Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendeli...
Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on ticagrelor, plasma proteomics and type 2 diabetes was employed to identify causal mediator proteins. RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells revealed the molecular pathways regulating glucose metabolism. Genetically proxied ticagrelor was significantly associated with a reduced risk of diabetes (OR = 0.859, 95% CI: 0.783-0.934, P = 7.98E-05), and 24.41% of this effect was mediated by upregulation of BDH2 protein. In vitro experiments confirmed the enhanced effect of ticagrelor on glucose consumption. Transcriptome analysis revealed that mitochondrial respiratory chain transfer and oxidative phosphorylation (OXPHOS) were significantly enriched, and genes related to ATP biosynthesis were significantly upregulated. These findings highlight the non-platelet function of ticagrelor in maintaining glucose homeostasis, providing insights into potential drug repurposing in the future.
Klotho Attenuates Glucocorticoid-Induced Osteoblast Cytotoxicity Via Wnt Signaling Pathway Modulation.
Wang S, He M, Liang X … +1 more , Li B
Biochem Genet · 2026 May · PMID 42159852 · Publisher ↗
Glucocorticoids are commonly prescribed in clinical settings; however, their prolonged use at high doses can adversely affect human health. One significant complication following glucocorticoid therapy is glucocorticoid-...
Glucocorticoids are commonly prescribed in clinical settings; however, their prolonged use at high doses can adversely affect human health. One significant complication following glucocorticoid therapy is glucocorticoid-induced osteoporosis (GIO), which is second in incidence only to senile osteoporosis. Based on previous research indicating that Klotho alleviates dexamethasone-induced osteoblast cytotoxicity through the NF-kB pathway, we aimed to explore the underlying mechanisms in greater depth. We assessed the impact of Lithium chloride (LiCl), a Wnt pathway activator, on glucocorticoid-induced cell cytotoxicity and viability. Cytotoxicity was specifically quantified by Annexin V/PI flow cytometry. We performed qRT-PCR and Western blotting analyzes to scrutinize the expressions of genes and proteins associated with both canonical and non-canonical Wnt signaling pathways. Dexamethasone treatment induced an upregulation of the non-canonical Wnt ligand, Wnt5a, and a downregulation of the canonical ligand, Wnt3a, along with its downstream marker, β-catenin. Transfection with Klotho counteracted these effects. Klotho has the potential to modulate both canonical and non-canonical Wnt signaling pathways, thereby counteracting osteoblast cytotoxicity induced by glucocorticoids.
CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.
Mayuri K, Saravanan KM, Somala CS … +3 more , Selvaraj C, Anand T, Vickram S
Biochem Genet · 2026 May · PMID 42154426 · Publisher ↗
CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the p...
CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the past decades in diagnostics, therapeutic genome editing, and vaccine development. The article highlights key platforms like DETECTR and SHERLOCK, which enable rapid, sensitive pathogen detection, and explores CRISPR-Cas9 systems in therapeutic strategies for directly targeting viral genomes and combating antimicrobial resistance. It also examines the role of CRISPR-Cas9 in engineering live-attenuated and personalized neoantigen vaccines. Principal findings demonstrate a clear progression from experimental proof-of-concept to preclinical applications primarily in CRISPR-based diagnostics and the engineering of live-attenuated vaccine candidates, whereas translation in CRISPR-based therapeutics and personalized neoantigen vaccines for infectious diseases remains at earlier, more exploratory stages. CRISPR-based diagnostics have progressed further toward clinical evaluation than therapeutics due to delivery and safety constraints, while personalized neoantigen vaccines are included mainly as an emerging, comparative concept for infectious diseases rather than a mature application. This review uniquely integrates CRISPR-based diagnostics, therapeutics, and vaccine development within a single infectious disease framework, critically assesses their current maturity, and systematically highlights technical, regulatory, and ethical barriers alongside realistic future priorities. The review concludes that while CRISPR-Cas holds transformative potential for infectious disease management, significant challenges in delivery efficiency, off-target effects, and ethical regulation must be addressed to ensure safe and equitable clinical translation.
Circular RNA Circ_0020236 Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration Through Modulating the MiR-1825/IKBKB Axis.
Liu J, Sun B, Cao P … +1 more , Zhou S
Biochem Genet · 2026 May · PMID 42126721 · Publisher ↗
Hepatocellular carcinoma (HCC) is one of the most metastatic and aggressive malignancies. Circular RNAs (circRNAs) are associated with the pathogenesis and prognosis of HCC. This study aimed to explore the role of circ_0...
Hepatocellular carcinoma (HCC) is one of the most metastatic and aggressive malignancies. Circular RNAs (circRNAs) are associated with the pathogenesis and prognosis of HCC. This study aimed to explore the role of circ_0020236 in HCC progression. Expression levels of circ_0020236, miR-1825, and IKBKB were assessed in HCC clinical samples and cell lines using quantitative real-time PCR. Bioinformatics predictions combined with dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays validated molecular interactions. Functional assays, including CCK-8, colony formation, and Transwell migration, were employed to evaluate cell proliferation and migration. The results indicated that circ_0020236 and IKBKB were significantly downregulated, whereas miR-1825 was upregulated in HCC. Ectopic expression of circ_0020236 suppressed HCC cell proliferation, migration, and tumor growth in vivo. Mechanistically, circ_0020236 functioned as a molecular sponge for miR-1825, which directly targeted IKBKB. Rescue experiments showed that miR-1825 overexpression reversed the tumor-suppressive effects of circ_0020236, while IKBKB knockdown abrogated the inhibitory phenotype induced by miR-1825 silencing. Furthermore, the RNA-binding protein ESRP2 was identified as a positive regulator of circ_0020236 biogenesis. In conclusion, our findings reveal that the ESRP2/circ_0020236/miR-1825/IKBKB axis plays a critical role in inhibiting HCC progression, positioning circ_0020236 as a promising therapeutic target for HCC intervention.
The Sonic Hedgehog Pathway is Activated in Cushing's Disease with USP8 Mutations.
Huang S, Xu Y, Zhou X … +2 more , Lu J, Cao X
Biochem Genet · 2026 May · PMID 42101757 · Publisher ↗
Cushing's disease (CD) is a neuroendocrine disorder characterized by excessive adrenocorticotropic hormone (ACTH) secretion from pituitary adenomas, closely associated with ubiquitin-specific protease 8 (USP8) mutations....
Cushing's disease (CD) is a neuroendocrine disorder characterized by excessive adrenocorticotropic hormone (ACTH) secretion from pituitary adenomas, closely associated with ubiquitin-specific protease 8 (USP8) mutations. This study aimed to investigate whether USP8 mutations activate the Sonic Hedgehog (SHH) pathway by deubiquitinating its key component Smoothened (SMO), thereby promoting ACTH production in CD. mRNA expression profiles of USP8-mutated and wild-type CD patients (GEO dataset GSE132982) were analyzed for differentially expressed genes, followed by GO and KEGG pathway enrichment. USP8 mutant/wild-type plasmids were transfected into HeLa cells. Co-immunoprecipitation and Western blot evaluated USP8-SMO interaction and SMO ubiquitination. RT-qPCR, luciferase reporter assays, and nuclear translocation analysis assessed SHH pathway gene expression and GLI2 transcriptional activity. Immunohistochemistry detected SMO/SHH proteins in 9 USP8-mutated and 9 wild-type pituitary adenomas. Primary tumor cells were treated with the SMO inhibitor cyclopamine, and POMC mRNA/ACTH secretion were measured by RT-qPCR/ELISA. Chromatin immunoprecipitation (ChIP) verified GLI2 binding to the POMC promoter. SHH pathway genes were significantly dysregulated in USP8-mutated CD. Mutant USP8 enhanced SMO interaction, reduced SMO ubiquitination, and upregulated SHH target genes, promoting GLI2 nuclear translocation/activity. SMO-positive cells were more frequent in mutated tumors, with unchanged SHH expression. Cyclopamine suppressed POMC/ACTH specifically in mutated cells, and ChIP confirmed GLI2-POMC promoter binding. USP8 mutations activate the SHH pathway via SMO deubiquitination, driving GLI2-mediated POMC transcription and excessive ACTH secretion in CD. Targeting the SHH pathway may offer a novel therapeutic strategy for USP8-mutated Cushing's disease.
Saikosaponin D Attenuates Postherpetic Neuralgia and Reduces Inflammation by Regulating Gut Microbiota in a Rodent Model.
Cai S, Sun C, Wu Q … +1 more , Yao X
Biochem Genet · 2026 May · PMID 42101756 · Publisher ↗
Saikosaponin D (SSD) is a triterpenoid saponin derived from Bupleuri Radix and has therapeutic potential for the treatment of neuropathic pain. This study investigates the roles and underlying mechanisms of SSD in cellul...
Saikosaponin D (SSD) is a triterpenoid saponin derived from Bupleuri Radix and has therapeutic potential for the treatment of neuropathic pain. This study investigates the roles and underlying mechanisms of SSD in cellular and mouse models of resiniferatoxin (RTX)-induced postherpetic neuralgia (PHN). C57BL/6 mice were randomly assigned into four groups: control, RTX, RTX + vehicle, and RTX + SSD. Mechanical and thermal sensitivity were assessed to evaluate pain behaviors. Gut microbiota was depleted using antibiotic treatment, and fecal microbiota transplantation was used to restore gut flora in RTX-treated mice that received either vehicle or SSD. In vitro, RTX-stimulated human neuroblastoma SH-SY5Y cells were used as a cellular model of PHN. TRPA1 expression levels in mouse dorsal root ganglion and SH-SY5Y cells were measured by RT-qPCR and immunofluorescence staining. The levels of proinflammatory cytokines were evaluated in serum samples and SH-SY5Y cells via RT-qPCR or ELISA. Western blot was performed to assess protein levels of genes involved in TLR4/NF-κB and JAK/STAT3 pathways. Results showed that SSD attenuated RTX-induced neuralgia in mice. In both in vitro and in vivo models, SSD significantly reduced TRPA1 expression and proinflammatory cytokine levels. The protective effects of SSD against neuralgia were abolished following antibiotic-mediated gut microbiota depletion in mice. Fecal microbiota transplantation from SSD-treated mice alleviated RTX-induced neuralgia and inflammation in PHN model mice. Moreover, SSD reduced TLR4 protein level and reduced phosphorylation ratios of NF-κB p65, STAT3, and JAK in the lumbar spinal cord of RTX-treated mice and in SH-SY5Y cells. In conclusion, SSD alleviates RTX-induced PHN and inflammation in mice by modulating gut microbiota via the TLR4/NF-κB and JAK/STAT3 pathways.
The Complete Mitochondrial Genome of a Newly Recorded Chinese Species of Diglyphus sabulosus (Hymenoptera: Eulophidae) and Insights into Its Phylogenetic Position.
Fang LC, Ge ZQ, Xi OY … +2 more , Mu ZL, Hu HY
Biochem Genet · 2026 Apr · PMID 42060053 · Publisher ↗
Diglyphus Walker, 1844 is an economically important genus which many species acting as biocontrol agents against agromyzid leafminer pests, but there is a lack of mitogenomic data on the evolutionary relationships within...
Diglyphus Walker, 1844 is an economically important genus which many species acting as biocontrol agents against agromyzid leafminer pests, but there is a lack of mitogenomic data on the evolutionary relationships within this genus, hindering a comprehensive understanding of its evolutionary history. We used traditional morphological methods to identify species, and present the first complete mitochondrial genome sequence and characterization of features of Diglyphus sabulosus and further infer its phylogenetic position based on the amino acid sequences of 13 protein-coding genes (PCGs). The complete mitochondrial genome of D. sabulosus is 15,690 bp in length, including 13 PCGs, 22 transfer RNA genes, 2 ribosomal RNA genes and a control region. The AT content of the whole genome sequence was 81.0%, indicating a significant AT bias. All protein-coding genes have the typical ATN as the start codon and TAA as the stop codon. Phylogenetic analysis inferred from the amino acid sequences of 13 PCGs revealed that all species within the family Eulophidae constituted a monophyletic clade, supporting the monophyly of this family. D. sabulosus and D. poppoea form a well-supported sister group, representing the species with the closest phylogenetic relationship within the analyzed taxa. In this study, the mitogenome structure was analyzed and the taxonomic status of D. sabulosus was clarified, thus providing a theoretical basis for understanding the phylogenetic relationships of Diglyphus.
Evolutionary and Structural Insights into Proline Metabolism Genes Associated with Salt Resilience in Mango.
Rastogi L, Bajpai A, Soni SK … +1 more , Muthukumar M
Biochem Genet · 2026 Apr · PMID 42060052 · Publisher ↗
This research aims to unravel the regulatory networks and adaptive molecular mechanisms that drive salinity resilience in mango cultivars with varying salt stress responses. The study examined the molecular characteristi...
This research aims to unravel the regulatory networks and adaptive molecular mechanisms that drive salinity resilience in mango cultivars with varying salt stress responses. The study examined the molecular characteristics of three key proline metabolism genes: pyrroline carboxylate synthetase (P5CS), pyrroline carboxylate reductase (P5CR), and pyrroline carboxylate dehydrogenase (P5CDH) in mango under salinity stress conditions. The homology search of assembled transcripts revealed orthologs within the Malvids clade, which includes the order Sapindales and the Anacardiaceae family. A total of 19 unigenes associated with glutamate-mediated proline biosynthesis were identified, comprising seven P5CS (three isoforms), ten P5CR, and two P5CDH coding sequences. Phylogenetic analysis demonstrated strong homology with Anacardiaceae mRNA, whereas genes from other plant families formed distinct clades. Notably, P5CDH displayed unique phylogenetic relationships within Anacardiaceae, with Mangifera indica and Pistacia vera clustering closely together. In contrast, P5CR sequences exhibited the highest variability and segregated into separate clusters from orthologs of other families and orders. P5CS was identified as a key regulator of proline biosynthesis, featuring conserved amino acid kinase (AAK) and aldehyde dehydrogenase (ADH) domains essential for osmotic adjustment. The predicted cytoplasmic localization of P5CS and P5CR proteins could be a valid explanation for proline accumulation under stress, while mitochondrial localization predicted for pyrroline carboxylate dehydrogenase (P5CDH) protein is likely to regulate proline turnover. When exposed to salt stress, all mango varieties studied significantly increased their pyrroline carboxylate synthetase (P5CS) and pyrroline carboxylate reductase (P5CR) gene activity to produce more proline, likely helping plants mitigate stress. The variety ‘Kurukkan’ showed the highest increase in both genes, suggesting its strong salt resilience associated to its high proline production. In contrast, ‘Amrapali’ increased its P5CDH gene activity, which breaks down proline, which may account for its decreased salt tolerance. The presence of multiple isoforms and lineage-specific divergence in proline biosynthesis genes underscores the importance of this pathway in stress adaptation. Proline pathway genes that are functionally validated through heterologous expression in model organisms could serve as valuable targets for genome editing aimed at developing rootstocks that tolerate salinity or could be utilized as potential genetic resources for breeding resistant varieties.
Identification of Key Genes Related to SUMOylation and Potassium Channels and Their Mechanism of Influence on Pulmonary Arterial Hypertension.
Gao L, Huang W, Wang Q … +1 more , Lei S
Biochem Genet · 2026 Apr · PMID 42060051 · Publisher ↗
SUMOylation and potassium channels have been implicated in pulmonary arterial hypertension (PAH). This study was designed to identify key hub genes associated with these pathways and investigate their mechanistic roles. ...
SUMOylation and potassium channels have been implicated in pulmonary arterial hypertension (PAH). This study was designed to identify key hub genes associated with these pathways and investigate their mechanistic roles. We integrated data from the GSE131793, GSE113439, and GSE228644 datasets to obtain candidate genes associated with SUMOylation and potassium channels. Machine learning algorithms and expression verification were employed to identify the hub genes. Subsequently, we constructed regulatory networks and performed single-cell analysis to annotate distinct cell populations. Cell communication and pseudotime analyses were then analyzed. Quantitative polymerase chain reaction (qPCR) validation was conducted on samples from 5 idiopathic PAH (IPAH) patients and 5 controls. An initial list of 26 candidate genes was obtained, which was then narrowed by our screening strategy to ATP1B1, CD151, HP, IL18RAP, and VSTM1. Of these, ATP1B1 and HP showed consistent expression trends and were defined as hub genes. Both genes were positively correlated with the Fc gamma R-mediated phagocytosis and Lysosome pathways. In the single-cell analysis, multiple cell types, including fibroblasts, monocytes/macrophages, and T cells, were annotated. Notably, epithelial cells interacted exclusively with fibroblasts in the control group. Pseudotime analysis suggested ATP1B1 and HP are involved in transitioning epithelial cells from normal to diseased states. qPCR confirmed significantly elevated expression of ATP1B1 and HP in PAH patients (p < 0.05). ATP1B1 and HP were identified as key hub genes in PAH, potentially influencing immune and inflammatory pathways during PAH development.
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