Anoikis is a new mode of cell death that has been shown to correlate significantly with tumors. However, the clinical prognostic significance of anoikis in lung squamous cell carcinoma (LUSC) remains Show more
Anoikis is a new mode of cell death that has been shown to correlate significantly with tumors. However, the clinical prognostic significance of anoikis in lung squamous cell carcinoma (LUSC) remains poorly studied. The differentially expressed ARGs and candidate genes were selected by the differential analysis to construct a predictive model. Independent prognostic gene was determined by Cox and LASSO analysis and we used the HCC95 and NCI H520 cell line to verify the gene function. We used the data from TCGA, GEO, GeneCards, and Harmonizome databases to analyze the immune microenvironment, functional enrichment, and drug sensitivity analysis. We identified 717 differentially expressed and selected 3 ARGs (FADD, SNAI1, and BAG4) to construct a predictive model. We found that SNAI1 is an independent prognostic gene and confirmed that knocking out the SNAI1 inhibited the HCC95 We used ARGs to construct a prognosis model for LUSC that can accurately predict the prognosis of LUSC patients. ARGs, especially SNAI1, play an essential role in developing LUSC. These findings could provide individualized treatment plans and new research ideas for LUSC patients. Show less
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a substantial global threat. SARS-CoV-2 nonstructural proteins (NSPs) are essential for impeding the host replication mechanism while Show more
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a substantial global threat. SARS-CoV-2 nonstructural proteins (NSPs) are essential for impeding the host replication mechanism while also assisting in the production and organization of new viral components. However, NSPs are not incorporated into viral particles, and their subsequent fate within host cells remains poorly understood. Additionally, their role in viral pathogenesis requires further investigation. This study aimed to discover the ultimate fate of NSP6 in host cells and to elucidate its role in viral pathogenesis. We investigated the effects of NSP6 on cell death and explored the underlying mechanism; moreover, we examined the degradation mechanism of NSP6 in human cells, along with analysing its correlation with coronavirus disease 2019 (COVID-19) severity in patient peripheral blood mononuclear cells (PBMCs). NSP6 was demonstrated to induce cell death. Specifically, NSP6 interacted with EI24 autophagy-associated transmembrane protein (EI24) to increase intracellular Ca This study reveals that KLHL22-mediated ubiquitination controls NSP6 stability and that NSP6 induces autophagic cell death via calcium overload, highlighting its cytotoxic role and suggesting therapeutic strategies that target calcium signaling or promote NSP6 degradation as potential interventions against COVID-19. Show less
Colorectal cancer (CRC) metastasis remains a major cause of mortality, driven by epithelial-to-mesenchymal transition (EMT) and invasion. Programmed cell death 4 (Pdcd4), a tumor suppressor, is known Show more
Colorectal cancer (CRC) metastasis remains a major cause of mortality, driven by epithelial-to-mesenchymal transition (EMT) and invasion. Programmed cell death 4 (Pdcd4), a tumor suppressor, is known to inhibit translation via interaction with eukaryotic initiation factor 4A (eIF4A). Previous studies have established that Pdcd4 suppresses stress-activated protein kinase 1-interacting protein 1 (Sin1) translation through the mTORC2-Akt axis, thereby downregulating Snail expression and EMT in CRC cells. However, whether Pdcd4 directly regulates Slug, another critical EMT transcription factor, remains unexplored. PDCD4 shRNA and SLUG siRNA were used to knock down Pdcd4 and Slug in colorectal cancer cells, respectively. The sucrose gradient fractionation was performed to determine SLUG translation. A luciferase reporter assay was used to determine the role of the SLUG 5' untranslated region (5'UTR) on Pdcd4 inhibition. The effect of Slug on promoting invasion was determined by Matrigel invasion assays. Knockdown of Pdcd4 in colorectal cancer cells increased Slug protein levels without altering SLUG mRNA abundance. Sucrose gradient fractionation revealed that Pdcd4 knockdown elevated the proportion of SLUG mRNA in polysome fractions, demonstrating Pdcd4-mediated suppression of SLUG translation. To validate the mechanism, the SLUG 5'UTR was cloned and fused to a luciferase reporter and named SLUG-5'UTR-Luc. Pdcd4 knockdown markedly enhanced SLUG-5'UTR-Luc activity; whereas, ectopic Pdcd4 expression suppressed it, indicating that the SLUG 5'UTR is critical for Pdcd4-mediated translational repression. Treatment with the eIF4A inhibitor silvestrol substantially reduced Slug protein levels and SLUG-5'UTR-Luc activity. In addition, Pdcd4 overexpression decreased Slug protein abundance and restored E-cadherin expression. Notably, Slug knockdown in Pdcd4-deficient cells rescued E-cadherin expression and abrogated the invasive phenotype. These findings suggest that up-regulation of Slug translation by Pdcd4 knockdown contributes to enhanced invasion. Pdcd4 suppresses colorectal cancer invasion by translationally downregulating Slug expression. Show less
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases Show more
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases such as obesity. Several randomized controlled trials (RCTs) targeting obese or overweight populations have found that individuals with different genotypes exhibit varying responses to the same lifestyle intervention (gene-lifestyle intervention interactions). To date, more than 20 genes, including Show less
Liver and lung are the most common metastatic sites in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a crucial role in the progression and metastasis of CRC. Understanding the Show more
Liver and lung are the most common metastatic sites in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a crucial role in the progression and metastasis of CRC. Understanding the interactions between various types of cells in the TME can suggest innovative therapeutic strategies. Using single-cell RNA sequencing (scRNA-Seq) and clinical samples, fibroblast growth factor-19 (FGF19, rodent FGF15) is found to mediate a significant interaction between CRC cells and cancer-associated fibroblasts (CAFs), activating the hepatic stellate cells (HSCs)-to-CAFs differentiation. In various CRC metastatic mouse models, it is shown that FGF15 has a more pronounced effect on liver metastasis compared to pulmonary metastasis. More importantly, the differentially expressed genes (DEGs) are also identified from the RNA-Seq dataset upon the activation of HSCs by FGF19 and compared the DEGs in matched primary and metastatic mRNA samples from patients with CRC liver metastasis (CRCLM), it is found that the ANGPTL4 gene is significantly associated with HSCs activation. Different mouse models also demonstrated the impact of the FGF19/ANGPTL4 axis on the severity of CRCLM. Importantly, disruption of this axis significantly inhibits CRCLM in vivo. This study is among the first to demonstrate the impact of the FGF19/ANGPTL4 axis on CRCLM, offering a novel therapeutic strategy. Show less
Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccha Show more
Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752. Structural analysis revealed that BVP1 is a neutral α-mannan consisting of a backbone of 1,2,6-linked α-D-Manp, with branches composed of T-linked α-D-Manp, 1,2-linked α-D-Manp, and 1,3-linked α-D-Manp. Animal experiments showed that BVP1 significantly alleviated hepatic steatosis, liver injury and inflammation, and enhanced antioxidant activity in MAFLD mice. Single-nucleus RNA sequencing analysis revealed that BVP1 could restore HFD-induced imbalances in liver sinusoidal endothelial cells, hepatic stellate cells, macrophages and Kupffer cells by upregulating the expression of the lipid degradation gene Cps1 and downregulating the expression of the lipid synthesis gene Acsl1 in these cell subpopulations. Interestingly, BVP1 reshaped the gut microbiota and fecal metabolite profile by enriching beneficial bacteria and associated metabolites including salicylic acid, spermidine, and 4-hydroxyphenyl acetate. Fecal microbiota transplantation experiments verified that the anti-MAFLD effects are mediated by the BVP1-modified gut microbiota. Our findings highlight the potential of BVP1 as a promising therapeutic agent for MAFLD treatment. Show less
To investigate the causal relationship between various lipid-modifying drugs and new-onset diabetes, as well as the mediators contributing to this relationship. Mediation Mendelian randomization was p Show more
To investigate the causal relationship between various lipid-modifying drugs and new-onset diabetes, as well as the mediators contributing to this relationship. Mediation Mendelian randomization was performed to investigate the causal effect of lipid-modifying drug targets on type 2 diabetes (T2D) outcomes and the proportion of this association that is mediated through ectopic fat accumulation traits. Specific sets of variants in or near genes that encode 11 lipid-modifying drug targets (LDLR, HMGCR, NPC1L1, PCSK9, APOB, ABCG5/ABCG8, LPL, PPARA, ANGPTL3, APOC3, and CETP; for expansion of gene symbols, use search tool at www.genenames.org) were extracted. Random effects inverse variance weighted were performed to evaluate the causal effects among outcomes. Mediation analyses were performed to identify the mediators of the association between lipid-modifying drugs and T2D. The study was conducted from November 10, 2023, to April 2, 2024 RESULTS: The genetic mimicry of HMGCR and APOB inhibition was associated with an increased T2D risk, whereas the genetic mimicry of LPL enhancement was linked to a lower T2D risk. Gluteofemoral adipose tissue volume was a mediator for explaining 9.52% (P=.002), 16.90% (P=.03), and 10.50% (P=.003) of the total effect of HMGCR, APOB, and LPL on T2D susceptibility, respectively. Liver fat was a mediator for explaining 21.12% (P=.005), 12.28% (P=.03), and 9.84% (P=.005) of the total effect of HMGCR, APOB, and LPL on T2D susceptibility, respectively. Our findings support the hypothesis that liver fat and gluteofemoral adipose tissue play a mediating role in the prodiabetic effects of HMGCR and APOB inhibition, as well as in the antidiabetic effects of LPL enhancement. Show less
Juvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insect
Nolan Priedigkeit, Beth Harrison, Robert Shue+27 more · 2025 · Clinical cancer research : an official journal of the American Association for Cancer Research · added 2026-04-24
Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to li Show more
Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to limited large-scale genomic studies that directly compare IBC with non-IBC cases. We conducted a retrospective analysis of 140 patients with IBC (68 primary tumors and 72 metastatic tumors) and 2,317 patients with non-IBC (700 primary tumors, 65 local recurrences, and 1,552 metastases). We compared clinicopathologic features, single-nucleotide variants, copy-number variants, tumor mutational burden, and exploratory survival outcomes between IBC and non-IBC tumors. The most frequent somatic alterations in IBC were detected in TP53 (72%), ERBB2 (32%), PIK3CA (24%), CCND1 (12%), MYC (9%), FGFR1 (8%), and GATA3 (8%). Multivariate logistic regression revealed a significant enrichment of TP53 single-nucleotide variants in IBC, particularly in HER2+ and hormone receptor-positive disease. Tumor mutational burden did not differ between IBC and non-IBC cases. In HER2+ disease, a pathway analysis revealed an enrichment of NOTCH pathway alterations. TP53, CCND1, and RB1 alterations were associated with poor outcomes in IBC. This study provides a comprehensive resource of somatic alterations in a large cohort of patients with metastatic IBC and non-IBC, highlighting genomic features associated with worse outcomes. Our findings reveal a significant enrichment of TP53 mutations, reinforcing its critical role in IBC pathogenesis. Few other distinct differences in IBC were observed, suggesting further investigations-beyond bulk sequencing of the somatic genome-are required to better understand the biology driving this aggressive disease. Show less
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune sys Show more
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune system due to anti-inflammatory properties. Tigecycline, an antibiotic of the glycylcycline class, is commonly used for severe infections. This study aimed to investigate tigecycline's mechanism on the inflammatory response of sepsis to find new targets for sepsis treatment. The objective included (i) to observe the changes in inflammatory factors in LPS (lipopolysaccharide) induced septic mice after tigecycline administration, (ii) to detect the effect of tigecycline on macrophages NF-κB (nuclear factor kappa B) signalling. For LPS-induced sepsis in mice and intervention with tigecycline, mice were first injected with tigecycline (6.5 mg/kg) via tail vein followed by LPS (15 mg/kg). Luminex analysis was performed on 16 mediators. NF-κB signalling pathway antibody chip detected the expression of target sites in macrophages of the LPS group and tigecycline + LPS group. Tigecycline has inhibitory effects on LPS-induced inflammatory response in septic mice, decreasing the concentrations of IL (interleukin)-6, IL-27, TNF-α (tumour necrosis factor-α), TNF RII, IFN-γ (interferon-gamma), CCL5/RANTES (CC Motif Chemokine Ligand) while increasing IL-6Rα, IL-10, and TWEAK (TNF-related weak inducer of apoptosis). Tigecycline downregulated phosphorylation levels of key sites JNK (c-Jun N-terminal kinase)1/2/3, p-p65 (s468) and p-p105/p50 (s907) in NF-κB signalling. Tigecycline may inhibit the excessive immune response induced by LPS in sepsis, which may cause a potential protective effect on the host through immune regulation. Show less
The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect Show more
The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect of 24-hour physical activities components on changing Life expectancy among patients with type 2 diabetes diagnosed. To address the abovementioned research gap, the study has a two-fold aims: first, to examine the mediation effect of 24-hour physical activities in type 2 diabetes and mortality; and second, to address how reallocating time on different daily activities would affect life expectancy. Analysis was conducted on the accelerometer data of 103,359 participants in the UK Biobank, with a median age of 57 years (range 39 to 70). Compositional mediation cox model was conducted to analyze the mediating effects of 24-hour physical activities. Additionally, the cohort Life table method was utilized to estimate the changes of Life-years over the next 10 years resulting from the substitution effect of different physical activities. During a mean follow-up of 13.95 (range 2.95-16.28) years, 2,649 deaths were recorded. Diabetes was significantly associated with increased time spent engaging in sedentary behavior (SB), and reduced time spent on moderate-to-vigorous physical activity (MVPA) and light-intensive physical activity (LPA), thereby demonstrating an association with higher mortality risk. The indirect effect of physical activity (HR = 1.27, 95% CI 1.23-1.30) accounted for 41.9% of the total effect of diabetes on mortality. Furthermore, the Life expectancy gains with a maximum of 1.32 years over the next 10 years was found when reallocating SB time to MVPA. The results revealed that 24-hour physical activities might mediate the association between diabetes and mortality. Therefore, promoting participation in MVPA and reducing sedentary activities among diabetes patients was expected to have a positive effect on Life expectancy over the next 10 years. Show less
Cognitive impairment is acknowledged as an early stage between normal aging and Alzheimer's disease, emphasizing the need for prompt intervention. There is growing evidence that the gut-brain axis pla Show more
Cognitive impairment is acknowledged as an early stage between normal aging and Alzheimer's disease, emphasizing the need for prompt intervention. There is growing evidence that the gut-brain axis plays a role in regulating cognitive function, indicating that probiotics and their derivatives may impact cognitive functions through the brain-gut axis. In this study, we isolated and identified a novel bacterial strain Show less
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive v Show more
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive virtual screening protocol that combines energy-based screening and machine learning techniques, leading to the identification of a novel compound, Show less
To observe the effect of the Lian-Dou-Qing-Mai (LDQM) formula on lipid metabolism in mice and explore its mechanism from the perspective of regulating the PPARγ/LXRα/ABCA1 signaling pathway. THP-1 cel Show more
To observe the effect of the Lian-Dou-Qing-Mai (LDQM) formula on lipid metabolism in mice and explore its mechanism from the perspective of regulating the PPARγ/LXRα/ABCA1 signaling pathway. THP-1 cells were induced to transform into foam cells with ox-LDL. Atherosclerosis (AS) models were constructed using a high-fat diet in ApoE In the cell model, LDQM could inhibit the formation of THP-1 macrophage-derived foam cells and the expression of inflammatory factors, promote macrophage cholesterol efflux, increase the expression of IL-10, and activate the PPARγ-LXRα-ABCA1/ABCG1 pathway. Additional IL-10 treatment further promotes LDQM-induced cholesterol efflux in THP-1 cells; LDQM may affect the PPARγ/LXRα/ABCA1 signaling pathway through IL-10, regulate lipid metabolism, reduce serum inflammatory expression and lipid deposition, and improve the formation of atheroplaques. Show less
Genome-wide association studies (GWAS) have identified nearly 100 loci associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the molecular functions of these variant al Show more
Genome-wide association studies (GWAS) have identified nearly 100 loci associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the molecular functions of these variant alleles remain elusive, particularly when they occur in non-coding regions. Here we profiled the chromatin accessibility landscape of liver nuclei from MASLD individuals, and demonstrated these accessible genomic sites were bound by cell type-specific transcription factors (TFs) and enriched for MASLD risk variants, highlighting lineage- and disease state-specific regulation. Using a massively parallel reporter assay (MPRA), we identified hundreds of differential activity variants (DAVs) that operate in a cell type-specific manner or in a stimulus-dependent context by disrupting liver pathogenesis-associated transcriptional regulatory network. Integrative analyses combining liver eQTLs, chromatin looping, and single-cell CRISPRi screening linked these DAVs to functional target genes. Notably, we demonstrated that DAVs located near Show less
Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have indep Show more
Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have independently evolved specialized musk-secreting glands, representing a striking case of convergent evolution. Through an integrated multi-omics approach, this study identified cyclopentadecanone as a shared key metabolic precursor in musk from both forest musk deer and muskrat, although downstream metabolite profiles diverged between the two lineages. Single-cell RNA sequencing revealed that these specialized apocrine glands possessed unique secretory architecture and exhibited transcriptional profiles associated with periodic musk production, distinct from those in conventional apocrine glands. Convergent features were evident at the cellular level, where acinar, ductal, and basal epithelial subtypes showed parallel molecular signatures across both taxa. Notably, acinar cells in both species expressed common genes involved in fatty acid and glycerolipid metabolism (e.g., Show less
To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of Show more
To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of glucocorticoids. Protopanaxadiol (PPD) possesses activity of dissociating transactivation from transrepression by glucocorticoid receptor (GR), which may serve as a potential selective GR modulator. However, steroid-like effects of PPD in vivo are unclear and not defined. How to translate PPD into clinical practice remains to be explored. The current study explored the renoprotection and potential mechanism of PPD and its combination with steroid hormones using adriamycin-induced NS rats. Adriamycin was given intravenously to rats to induce nephropathy. The determination of proteinuria, biochemical changes and inflammatory cytokines were performed, and pathological changes were examined by histopathological examination. Immunostaining and PCR were used to analyze the expression of interesting proteins and genes. The results showed that PPD, alone and in combination with prednisone, efficiently alleviate the symptoms of NS, attenuate nephropathy, improve adriamycin-induced podocyte injury by reducing desmin and increasing synaptopodin expression. In addition, the combined treatment reduced the expression of NF-κB protein and mRNA, as well as cytokine levels, and yet increased the expression of GR protein and mRNA. PPD modulated the transactivation of GR, manifested as repressing TAT, PEPCK and ANGPTL4 mRNA expressions mediated by GR. Meanwhile, PPD inhibited elevation of blood glucose and immune organ atrophy induced by prednisone. In summary, PPD increases the therapeutic effect of prednisone in NS while effectively prevents or decreases the appearance of side effects of glucocorticoids. Show less
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are widely found in organisms and play an important regulatory role in various biological processes, especially immune and infla Show more
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are widely found in organisms and play an important regulatory role in various biological processes, especially immune and inflammatory responses. However, the function of miR-320b in the inflammatory responses of bovine mammary epithelial cells (bMECs) remains to be elucidated. In this study, we examined the miR-320b mimic transduction group (miR-320b_mimic) and negative control mimic transduction group (NC_mimic) of lipopolysaccharide-treated bMECs using data-independent acquisition (DIA) proteomics and untargeted metabolomics. Subsequently, we performed a joint analysis of the sequencing data. Proteomic analysis identified 330 differentially abundant proteins (DAPs) primarily related to PPAR, ferroptosis, arachidonic acid metabolism, IL-17, and complement and coagulation cascades. Metabolome analysis identified 128 and 66 differentially accumulated metabolites (DAMs) in the positive and negative ion mode primarily involved in linoleic acid metabolism, cholesterol metabolism, AMPK, MAPK, and chemokine. Integrated metabolomics and proteomics analysis revealed the co-enrichment of DAPs and DAMs in choline metabolism in cancer, endocrine resistance, glycerophospholipid metabolism, primary bile acid biosynthesis, and the ferroptosis signaling pathways. The results of quantitative real-time PCR (RT-qPCR) showed that compared with the NC_mimic group, mRNA expression levels of COX-2, IL-12 A, iNOS, MAPK1, and MAPK14 genes were significantly down-regulated, and the mRNA expression levels of PPARγ, CEBPα, CEBPβ, FABP4, and LPL genes were significantly up-regulated in the miR-320b_mimic group. These results provide crucial insights into the molecular regulatory functions of miR-320b and offer valuable data for further research on molecular breeding aimed at enhancing mastitis resistance in bovine animals. Show less
Yuwen Guo, Huai Bai, Linbo Guan+4 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 Show more
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect. Show less
Xiang Lian, Xiaoyan Li, Kexin Wang+3 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestation Show more
To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestations and gene variation. Two patients (patient 1 and 2) with FH who visited Beijing Anzhen Hospital Affiliated to Capital Medical University in 2018 were selected as research subjects. A retrospective study method was used to collect clinical and family history data of the two patients. And 2 mL of peripheral venous blood from each of the two patients was collected, and genomic DNA extraction was performed on the blood samples. Sanger sequencing was used to validate the variant sites of the two patients detected by whole-exome sequencing (WES). Pathogenicity of variants was classified based on the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the "ACMG Guidelines"), and the impact of variant was analyzed using multiple bioinformatics tools including SIFT, PolyPhen-2, and SWISS-MODEL. This study has been approved by Beijing Anzhen Hospital Affiliated to Capital Medical University (Ethics No. 2024215X). Patient 1 initially presented with early-onset coronary heart disease, with initial lipid levels of serum total cholesterol (TC) 9.86 mmol/L (normal reference value: 3.10~5.20 mmol/L) and serum low-density lipoprotein cholesterol (LDL-C) 8.37 mmol/L (normal reference value: 1.27~3.12 mmol/L) on admission. Patient 1 initially underwent treatment with rosuvastatin combined with ezetimibe for one month, but the lipid-lowering effect was not significant. The lipid-lowering therapy was then adjusted to atorvastatin combined with ezetimibe and probucol. After one year of treatment, the patient developed paroxysmal chest pain symptoms. A follow-up lipid profile showed a serum TC level of 4.50 mmol/L and a LDL-C level of 3.55 mmol/L. The lipid-lowering regimen was continued, and the serum LDL-C levels were maintained between 2.65 and 3.66 mmol/L. Patient 2 was found to have an abnormally high blood lipid level and carotid artery hardening during physical examination, with an initial blood lipid level of serum TC 11.82 mmol/L and serum LDL-C 9.63 mmol/L. After receiving rosuvastatain therapy, the lipid-lowering effect was significant. WES revealed that patient 1 carried the heterozygous variants c.1871₁₈₇₃del(p.Ile624del) and c.1747C>T (p.His583Tyr) in the LDLR gene (NM₀₀₀₅₂₇.4), while patient 2 carried the heterozygous variants c.1747C>T (p.His583Tyr) in the LDLR gene and c.6936₆₉₃₇inv (p.Ile2313Val) in the APOB gene (NM₀₀₀₃₈₄₎. According to the ACMG Guidelines, the LDLR gene c.1747C>T (p.His583Tyr) was classified as a pathogenic variant (PS3+PM1+PM2_supporting+PM5+PP2+PP3), and c.1871₁₈₇₃del (p.Ile624del) was classified as a pathogenic variant (PS3+PS4+PM2_supporting+PM1+PM4); the APOB gene c.6936₆₉₃₇inv (p.Ile2313Val) was classified as a variant of uncertain clinical significance (PM2_supporting BP4). Patients 1 and 2 in this study were patients with complex heterozygous variant FH, and their genotypic differences may be related to the differences in clinical serum LDL-C levels and the efficacy of hypolipidemic agents. Show less
The malignant transformation of odontogenic keratocysts (OKC) into cancerous odontogenic keratocysts (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cell Show more
The malignant transformation of odontogenic keratocysts (OKC) into cancerous odontogenic keratocysts (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cellular heterogeneity, molecular pathways, and clinical features of COKC are limited. In this study, we performed single-cell RNA sequencing (scRNA-seq) on three COKC samples and integrated the data with a public OKC dataset, identifying 22,509 single cells. Two COKC-specific epithelial subpopulations, Basal-C0-EXT1 and Basal-C3-HIST1H3B, were identified. These subpopulations exhibited enhanced stemness and invasive potential, respectively, suggesting their roles as key drivers of OKC carcinogenesis. Fibroblasts underwent phenotypic transitions, particularly from inflammation-associated fibroblasts (IFBs) to myofibroblasts (MFBs). Similarly, macrophage phenotypic transformation may also play a role in OKC carcinogenesis. Clinical observations of severe lesion-area pain in COKC patients suggest potential neuroinvasiveness, Supported by single-cell transcriptomic data, imaging findings, and histopathological evidence. A review of clinical data revealed that none of the COKC patients exhibited cervical lymph node metastasis. Single-cell transcriptomics suggests that this phenomenon may be associated with an active immune microenvironment in COKC, reduced epithelial-mesenchymal transition (EMT) activity, lower VEGFC expression, and upregulated MAST4 expression as a potential regulator of lymphatic metastasis. In conclusion, COKC exhibits distinct molecular, cellular, and clinical characteristics compared to OKC, featuring potent neuroinvasiveness and low lymph node metastatic potential. These findings provide important insights into the mechanisms underlying COKC development and may guide novel diagnostic and therapeutic strategies. Show less
Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolem Show more
Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolemia and has been approved for use in the Chinese population. Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease, and traditional treatments often fall short due to challenges such as statin intolerance. Clinical trials have demonstrated that tafolecimab can effectively reduce LDL-C levels, achieving reductions of over 60% in many patients. It also improves other lipid parameters, including lipoprotein(a) [Lp(a)], non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (ApoB). It has a favorable safety profile, primarily characterized by mild to moderate adverse events. The long-acting formulation of tafolecimab enables less frequent dosing, thereby promoting compliance. As cardiovascular diseases continue to escalate globally, tafolecimab holds promise not only for patients in China but also for broader international applications, representing a critical advancement in the evolving landscape of lipid-lowering therapies. Show less
Cordyceps has been clinically used to treat atherosclerosis (AS) since the 1980s. However, the active components responsible for its effects and the underlying mechanisms remain poorly understood. In Show more
Cordyceps has been clinically used to treat atherosclerosis (AS) since the 1980s. However, the active components responsible for its effects and the underlying mechanisms remain poorly understood. In this study, we aimed to explore the anti-AS effects and mechanisms of action of wild Cordyceps polysaccharides (WCP). The molecular weight, monosaccharide composition, and structural characteristics of WCP were analyzed. Furthermore, the anti-AS effects of WCP were evaluated using apolipoprotein E knockout ( Show less
This study aimed to explore active ingredients in Scrophularia ningpoensis Hemsl (SNH) with potential effects on ameloblastoma (AM) using network pharmacological approach, bioinformatic gene analysis Show more
This study aimed to explore active ingredients in Scrophularia ningpoensis Hemsl (SNH) with potential effects on ameloblastoma (AM) using network pharmacological approach, bioinformatic gene analysis and in vitro cell experiments. The active ingredients and their corresponding targets of SNH were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP), as well as SwissTargetPrediction. Disease targets of AM were selected from GeneCards and DisGeNET databases. Differentially expressed genes (DEGs) of AM were identified, and Gene Ontology enrichment analysis were performed using the Gene Expression Omnibus (GEO) dataset GSE38494 through bioinformatic analysis. The STRING database platform was utilized to generate a protein-protein interaction network diagram, followed by hub gene analysis using Cytoscape software. AutoDock Vina software was used to perform molecular docking verification of the effects of the active ingredients on potential core targets. Additionally, in vitro experiments including quantitative reverse transcription polymerase chain reaction (RT-qPCR), EdU assay and CCK-8 cell proliferation assay were conducted using AM cell line AM-1 after SNH extract treatment. The study revealed that SNH contains eight active ingredients and a total of 388 drug targets, including 10 potential core targets in AM. Hub genes identified in the analysis were CCNA2, HRAS, PTGS2, PIK3CB, FGFR1, CASP3, MMP1, SLC2A1, MMP14, and MME. Molecular docking analysis demonstrated strong binding activity between key active ingredients (β-sitosterol, scropolioside A_qt, scropolioside D, scropolioside D_qt, and sugiol) and target genes (CASP3, FGFR1, HRAS, PTGS2, and SLC2A1). Gene Ontology enrichment analysis indicated that SNH exerts its effects on AM through pathways related to cellular response to abiotic stimulus, cellular response to hypoxia, and exopeptidase activity. Immunohistochemical analysis using tissue microarray showed higher expression of MMP14 and PTGS2 in AM compared to dentigerous cyst. Using AM-1 cell line, RT-qPCR results confirmed that SNH suppressed the expression of MMP14 and PTGS2 at mRNA level. Additionally, the EdUassay and CCK-8 assay indicated the inhibitory effect of SNH on the proliferation of AM-1 cells. These findings showed that SNH could suppress expression of MMP14 and PTGS2 and restrain the proliferation of AM. Our study highlights the potential of SNH as a promising therapeutic candidate for AM, which may provide more options for clinical treatment. Show less
Muscle wasting, characterized by loss of muscle mass and strength, severely impacts patient quality of life and is associated with numerous chronic diseases and aging. The molecular mechanisms are com Show more
Muscle wasting, characterized by loss of muscle mass and strength, severely impacts patient quality of life and is associated with numerous chronic diseases and aging. The molecular mechanisms are complex, involving protein synthesis/degradation imbalance. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and ubiquitin-specific peptidase 7 (USP7) have diverse cellular roles, but their coordinated function in skeletal muscle homeostasis remains poorly understood. DYRK1A overexpression in vivo induced muscle atrophy phenotypes, including reduced muscle mass, grip strength, fiber cross-sectional area (CSA), altered fiber type composition, and neuromuscular junction integrity, accompanied by elevated atrophy markers: muscle atrophy F-box protein (Atrogin-1), muscle ring finger 1 (MuRF-1), myostatin and suppressed myogenic markers: myoblast determination protein 1 (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (Mef2c), myogenic factor 5 (Myf5). Conversely, pharmacological inhibition of DYRK1A with Harmine ameliorated these atrophy phenotypes in transgenic DYRK1A overexpressing (TgD) mice. In vivo, USP7 deficiency resulted in similar muscle wasting phenotypes. In vitro, DYRK1A overexpression or USP7 overexpression inhibited C2C12 myoblast proliferation and differentiation, effects rescued by Wnt3a treatment or USP7 knockdown, respectively. Mechanistically, DYRK1A activity suppressed active β-catenin levels. USP7 was found to interact with and deubiquitinate axis inhibition protein 1 (Axin1), leading to its stabilization. Knockdown of USP7 increased Axin1 ubiquitination and degradation, thereby promoting β-catenin signaling and myogenesis, counteracting the effects of DYRK1A. Our findings reveal a novel signaling axis where DYRK1A and USP7 cooperatively suppress Wnt/β-catenin signaling to promote muscle wasting. DYRK1A likely acts upstream, potentially phosphorylating pathway components, whereas USP7 stabilizes the β-catenin destruction complex scaffold protein Axin1 through deubiquitination. This coordinated action inhibits myogenesis and activates atrophy pathways. Targeting DYRK1A or USP7 could represent promising therapeutic strategies for muscle wasting disorders. Show less
This study aimed to investigate the effect of lipoprotein(a) (Lp(a)) on major adverse cardiovascular events (MACEs) among individuals with chronic coronary syndrome (CCS) according to ABO blood groups Show more
This study aimed to investigate the effect of lipoprotein(a) (Lp(a)) on major adverse cardiovascular events (MACEs) among individuals with chronic coronary syndrome (CCS) according to ABO blood groups. Two independent cohorts of patients with CCS were included consecutively. Blood groups and Lp(a) levels were measured. Patients with the AB group were excluded due to the small sample size. In the exploratory cohort ( Show less
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide and lacks biomarkers for personalized therapy. Herein, it is reported that MCB1 could be a novel oncofetal Show more
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide and lacks biomarkers for personalized therapy. Herein, it is reported that MCB1 could be a novel oncofetal protein that is upregulated in the preneoplastic lesions and serum of early HCC patients. Functional studies reveal that MCB1 modulated p53 protein degradation to promote T-IC generation and drive HCC initiation. Furthermore, the MCB1/p53 axis is shown to determine the responses of hepatoma cells to conventional chemotherapeutics and predict transcatheter arterial chemoembolization (TACE) benefits in patients. Importantly, MCB1 can mediate sorafenib/lenvatinib resistance by downregulating two essential drug targets fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 3 (VEGFR3) expression in a proteasome-dependent manner. Patient-derived tumor organoids (PDOs), patient-derived xenografts (PDXs), and patient cohorts analysis suggested that MCB1 levels in HCCs may determine the distinct responses to conventional therapeutics and targeted drugs. Furthermore, treatment of targeted drugs-resistant HCC with adeno-associated virus (AAV) targeting MCB1 or a proteasome inhibitor restores targeted drug response, suggesting their clinical significance in HCC combinational therapy. In conclusion, these findings demonstrate that MCB1 could act as a driver for HCC initiation, a contributor to drug resistance, and a biomarker for individualized HCC therapy. Show less
Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality. Herein we present 12 Show more
Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality. Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children's Medical Center of Peking University First Hospital from September 2014 to August 2023. Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506₃₅₀₈del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing. Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1. Show less
Ran Zhao, Fanxiang Yin, Mangaladoss Fredimoses+12 more · 2024 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a me Show more
Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10-30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1's function in CRC and to create potent therapies that specifically target FGFR1. This study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of β,β-dimethylacrylalkannin (β,β-DMAA) as a therapeutic option to inhibit FGFR1. In this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. In our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that β,β-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that β,β-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, β,β-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with β,β-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, β,β-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors. Show less
This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated p Show more
This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles. A total of 93 han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing. Concurrently, multiple lipid parameters were measured and analyzed. Among these Han Chinese CHD patients, the PLA2G7 gene rs1051931 (c.1136T>C p.Val379Ala) rare variant was highly prevalent (variant rate: 94.62%) among the study population, and showed negative correlation with serum Lp-PLA2 activity. The rs1765208290 (c.233G>A p.Gly78Asp) rare variant showed positive correlation with TG, ApoA, ApoB, HDL, LDL and TCHO levels in the serum. Strong linkage disequilibrium was observed between the rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe), both of which were related to lower Lp-PLA2 activity. In these Han Chinese CHD patients, the rs1051931 (c.1136T>C p.Val379Ala) rare variant in the PLA2G7 gene is closely linked to decreased Lp-PLA2 activity, whereas the rs1765208290 (c.233G>A p.Gly78Asp) rare variant influences lipid homeostasis. The strong LD between rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe) loci may act synergistically to reduce Lp-PLA2 activity. Show less