Search Results (1,501)

In individuals with diabetes, dysregulation of inflammatory processes hinders the progression of wounds into the proliferative phase, resulting in chronic, non-healing wounds. Total saponins from Rhizoma Panacis majoris (SRPM), bioactive compounds naturally extracted from the rhizome of Panax japonicus C.A.Mey. var. major (Burk.) C.Y.Wu and K.M.Feng, have demonstrated extensive anti-inflammatory and immunomodulatory properties. This study aims to elucidate the molecular mechanisms underlying the facilitative effects of SRPM on diabetic wound healing, with particular emphasis on its anti-inflammatory actions. A high-fat diet combined with streptozotocin (STZ) administration was used to induce type 2 diabetes in rats. After two weeks of oral treatment with SRPM suspension, a wound model was established. Subsequently, a two-week course of combined local and systemic therapy was administered using both SRPM suspension and SRPM gel. SRPM markedly reduces the levels of pro-inflammatory mediators, including IL-1α, IL-1β, IL-6, MIP-1α, TNF-α, and MCP-1, in both rat tissues and serum. Concurrently, it increases the expression of anti-inflammatory cytokines such as IL-10, TGF-β1, and PDGF-BB, while also enhancing the expression of the tissue remodelling marker bFGF. Additionally, SRPM significantly decreases the accumulation of apoptotic cells within tissues by downregulating the pro-apoptotic gene Caspase-3, upregulating the anti-apoptotic gene Bcl-2, and increasing the expression of the apoptotic cell clearance receptor MerTK. Moreover, SRPM inhibits neutrophil infiltration and the release of neutrophil extracellular traps (NETs) in tissues, promotes macrophage polarisation towards the M2 phenotype, and activates the Wnt/β-catenin signalling pathway at the molecular level. SRPM promotes the healing of wounds in diabetic rats potentially due to its anti-inflammatory properties. Full article

Previous studies have shown that miR-5110 regulates pigmentation by cotargeting melanophilin (MLPH) and WNT family member 1 (WNT1). In order to find the possible molecular mechanism for pigmentation, we examined the mRNA expression profiles in melanocytes of alpaca transfected with miR-5110, inhibitor or negative control (NC) plasmids using high-throughput RNA sequencing. The results showed that a total of 91,976 unigenes were assembled from the reads, among which 13,262 had sequence sizes greater than 2000 nucleotides. According to the KEGG pathway analysis, four pathways related to melanogenesis, the MAPK signaling pathway, Wnt signaling pathway, and cAMP signaling pathway were identified. Compared to the NC, 162 gene were upregulated and 41 genes were downregulated in melanocytes over expressed by miR-5110. The differential expressions of mRNAs Dickkopf 3 (DKK3), premelanosome protein (Pmel), insulin-like growth factor 1 receptor (IGF1R), cyclin-dependent kinase 5 (CDK5), endothelin receptor type B (Ednrb), kit ligand (Kitl), Myc, and S100 were verified using qRT-PCR, which agreed with the results of RNA sequencing. We also verified the differential expressions of mRNAs of some genes in the MAPK signaling pathway using qRT-PCR, which agreed with the results of RNA sequencing. Interestingly, several genes were screened as candidates for the melanogenesis regulated by miR-5110, including Kitl and MAPK-activated protein kinase 3 (MAPKAPK3). These findings provide new insights for further molecular studies on the effects of miR-5110 on the melanogenesis and pigmentation. Full article

Background: Hair loss (alopecia) is primarily driven by the premature transition of hair follicles from the anagen (growth) to the catagen (regression) phase. Intracellular calcium signaling is implicated in hair follicle biology, including the regulation of Wnt/β-catenin activity and the modulation of catagen-associated factors such as TGF-β2. Cyclic ADP-ribose (cADPR), a calcium-mobilizing second messenger synthesized by CD38, has recently emerged as a potential modulator of intracellular calcium dynamics. This study investigated whether cADPR is associated with changes in intracellular calcium retention and anagen-associated signaling pathways in human hair follicle dermal papilla cells (HHDPCs). Methods: HHDPCs were treated with cADPR (0.001–0.5 ppm) and analyzed for cell viability, intracellular calcium retention, β-catenin-dependent transcription, and the gene expression of LEF-1 and TGF-β2. Cell viability was evaluated using the MTT assay, intracellular calcium content was quantified by ICP–OES, β-catenin activation was assessed using a TOPFlash luciferase assay, and gene expression was measured by qRT-PCR. Results: cADPR did not induce marked cytotoxicity, maintaining more than 98% cell viability across all concentrations. The highest response was observed at 0.05 ppm, at which intracellular calcium content remained elevated for up to six hours as assessed by ICP–OES. At this concentration, β-catenin-dependent transcription increased by approximately 2.3-fold relative to control, LEF-1 expression was significantly upregulated (~2.5-fold), and TGF-β2 expression was significantly downregulated (~0.3-fold). These responses showed an overall concentration-dependent trend across assays. Conclusions: These findings indicate an association between cADPR treatment and modulation of intracellular calcium retention and anagen-related signaling readouts in HHDPCs, supporting the need for further studies to establish mechanistic causality and physiological relevance. Full article

Natural compounds, as honey-derived flavonoids and phenolic compounds, are increasingly investigated for their potential to mitigate skin aging and prevent oxidative stress-induced cellular damages. In this context, a dynamic cell culture model was employed to assess the protective influence of honey pre-treatment on stem cell–associated genes and the Wingless-related integration site (Wnt) signaling pathway following ultraviolet (UV)-induced aging. Using a bioreactor, skin stem cells (SSCs) derived from healthy skin biopsies and human skin fibroblasts (HFF1) were pre-treated with 1% honey for 48 h and then exposed to UV. Real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed on Wnt signaling and anti-aging molecular responses. Honey pre-treatment enhanced the expression of pluripotency markers (Octamer-binding transcription factor 4 (Oct4); SRY-box transcription factor 2 (Sox2)) and reduced senescence-related cell cycle regulators (cyclin-dependent kinase inhibitor 2A (p16); cyclin-dependent kinase inhibitor 1A (p21); tumor protein 53 (p53)) in SSCs. In UV-damaged SSCs, honey also significantly increased Wnt3a expression. In fibroblasts, honey pre-treatment upregulated Heat shock protein 70 (Hsp70) and Hyaluronan synthase 2 (HAS2) expression, while downregulating caspase-8 (CASP8), indicating a protective role against UV-mediated cellular stress. We also analyzed nitric oxide release and the total antioxidant capacity of cells after treatment. Collectively, these findings suggest that honey may safeguard skin stem cells from UV-induced aging by modulating pluripotency and senescence-associated genes and regulating differentiation through alterations in Wnt signaling. Furthermore, Hsp70 upregulation in fibroblasts appears to strengthen cellular stress responses and support homeostatic stability. Full article

Secreted frizzled-related protein 3 (sFRP3/FRZB) is a soluble Wnt antagonist with established roles in skeletal development, however, its specific function in myogenesis remains underexplored. This study investigated the regulatory role of FRZB in muscle development, hypothesizing that it contributes to breed-specific growth differences in pigs. We examined FRZB expression in fetal tissues of slow-growing (Tibetan and Wujin) and fast-growing (Large White) pigs, and assessed its function in C2C12 myoblasts via siRNA-mediated knockdown. FRZB was widely expressed across porcine fetal tissues, with significantly higher abundance in the longissimus dorsi of slow-growing breeds. In vitro, FRZB silencing significantly enhanced myoblast proliferation and migration. Furthermore, knockdown accelerated differentiation and promoted the formation of longer, thicker multinucleated myotubes, accompanied by the upregulation of myogenic (MyoD, MyoG, MyHC) and fusion (β1-integrin, Myomaker) markers. Transcriptional profiling revealed a shift toward hypertrophy (Fst and Nog upregulation) and away from atrophy (Atrogin1 downregulation). These findings identify FRZB as a negative regulator of myogenesis via the Wnt signaling pathway. The elevated expression in indigenous breeds suggests FRZB may impose a molecular constraint on muscle development, highlighting its potential as a candidate gene for regulating carcass traits. Full article

Although the clownfish, Amphiprion ocellaris (A. ocellaris), is a popular ornamental marine fish worldwide, the mechanisms underlying color pattern variation remain unclear. Given that the Platinum-type clownfish, nearly entirely white, has high economic value, understanding the biological mechanism that accounts for the difference between orange and white colors in A. ocellaris is crucial. To investigate these coloration differences, we performed RNA sequencing analysis and identified differentially expressed genes (DEGs) by comparing white and orange skin samples from three A. ocellaris individuals. A total of 76 DEGs were detected, including 56 downregulated and 20 upregulated genes. DEG sequences were annotated using Danio rerio and Stegastus partitus as reference species, selecting the best hit based on the lowest E-value. A protein–protein interaction (PPI) network and Gene Ontology biological process terms were additionally analyzed. Several DEGs previously reported to be associated with pigmentation, including hpdb, cldn11b, sfrp5, slc2a9, slc2a11b, si:ch211-256m1.8, fhl2, rab38, and ttc39b were identified. Based on the functions of these DEGs, it is inferred that leucophores and xanthophores contribute to both white and orange coloration by modulating related genes, including slc2a11b and slc2a9. Additionally, sfrp5, sost, and sp7 genes were identified to interact with each other in the PPI analysis, with sfrp5 and sost being associated with the Wnt signaling pathway, which contributes to melanocyte specification and osteoblast differentiation. Based on these findings, we propose sost and sp7 as candidate genes that might provide insights relevant to extreme white pigmentation phenotypes, such as those observed in Platinum-type clownfish. For a clearer understanding, further studies integrating quantitative genetics and functional analyses are required. Full article

Abdominal fat deposition in chickens significantly impacts production efficiency and is influenced by complex genetic and molecular mechanisms. This review summarizes current genomic and transcriptomic research on the regulation of adipogenesis and fat accumulation in chickens, highlighting key genes and loci identified through genome-wide association studies as well as other candidates involved in lipogenesis, lipolysis, and transcriptional regulation. Major metabolic pathways, including MAPK, AMPK, PI3K/AKT/mTOR, TGFβ1/Smad3, FoxO, JAK–STAT, Wnt/β-catenin, and Sonic Hedgehog signaling, are examined for their roles in fat deposition. The regulatory functions of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are discussed, focusing on their interactions with target mRNAs and signaling networks that control lipid metabolism, adipocyte differentiation, and energy balance. Integrating insights from both avian and human studies, this review emphasizes the molecular mechanisms underlying adipogenesis and highlights potential strategies for genetic selection aimed at reducing excessive abdominal fat and improving poultry productivity. Full article

Silkie (SK) chickens, valued for dark meat, serve as a model to study melanin deposition in muscle. Integrated transcriptomics and metabolomics of SK vs. Arbor Acres (AA) broiler pectoralis were used to identify key molecular drivers of meat color. All birds were cage-raised under standardized temperature and light conditions with free access to feed and water. Pectoralis muscle samples were collected from 24-day-old healthy SK and AA chickens (n = 6). Transcriptome profiling identified 488 differentially expressed genes in SK chickens, with seven conserved melanogenesis genes (TYRP1, MLANA, TYR, MLPH, EDNRB2, PMEL, GPNMB) consistently upregulated across dark-pectoralis breeds, and melanogenesis and WNT pathways were activated. Co-expression network analysis highlighted SOX10 as a key hub regulator. Metabolomics quantified 129 differentially abundant metabolites. A critical finding was the significant depletion of L-tyrosine and its derivatives in SK muscle, despite upregulated melanogenesis genes. It indicates intense metabolic flux toward pigment synthesis. Integrated analyses converged on tyrosine metabolism and redox pathways: oxidized glutathione and p-coumaric acid correlated negatively with pigment deposition, while ADP-ribose and pyridoxal correlated positively. Additionally, novel inhibitors PNMT and HIBADH may modulate melanin deposition. These findings reveal a trade-off between pigment deposition and redox balance, providing molecular markers for poultry melanin-related trait improvement. Full article

Chronic ulcerative colitis disrupts mucosal-acquired immunity; however, the relationship between mucosal regeneration and mucosa-associated lymph tissue (MALT) development remains unclear. We explored crypt responses, MALT phenotypes, and regulatory T cells (Tregs) in a mouse model of chronic colitis following two cycles of dextran sodium sulfate (DSS) exposure. The mucosal regeneration score correlated with crypt expression of Ki-67 and LGR5, submucosal FOXP3-positive Treg expression, and MALT scores. MALT can be categorized into solitary-isolated lymphoid structures, tertiary lymphoid structures, and colonic patches. Regenerative crypts adjacent to tertiary lymphoid structures exhibit reduced expression of Ki-67, LGR5, and SOX9, which might favor mucosal differentiation. These findings were further supported by correlations between crypt stem cell- and Treg-related colonic gene expression of Lgr5, Sox9, Wnt6, Ccl20, and IL10, and between Tgfb1 and Cxcl13. These results suggested that chronic colitis is repaired by stem cell-mediated mucosal regeneration and differentiation, potentially driven by the development of MALT-containing Tregs. Full article

Background/objectives: Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis. Methods: To explore the underlying molecular mechanisms, we used a model based on primary ASCs derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells. Results: Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix (ECM) gene expression in ASC. We investigated the function of two markers of the fibroblastic transition highly induced by cancer cells: a long non-coding RNA LINC01614 and a Wnt signaling modulator SFRP4. By using ASCs with either SFRP4 or LINC01614 knocked out (ko), we showed that both genes are required for Wnt/TGFβ signaling and ECM induction in ASCs by Capan-1. Analysis of changes in Capan-1 genes that rely on LINC01614 and SFRP4 expression in ASCs also identified the Wnt and TGF pathways. SFRP4 ko in ASCs suppressed both migration and invasion of Capan-1 cells. We show that tumors in SFRP4 ko mice have less desmoplasia, less epithelial dedifferentiation, reduced growth rate, and reduced progression to metastasis. Conclusions: We conclude that SFRP4 promotes cancer progression in pancreatic cancer and is a promising therapeutic target. Full article

Objectives: To systematically analyze the expression profiles of long non-coding RNAs (lncRNAs) in serum-derived exosomes from patients with age-related hearing loss (ARHL), and to further identify key regulatory lncRNAs involved in the pathogenesis and progression of ARHL. Methods: Peripheral blood samples were collected from patients with ARHL and age-matched normal-hearing controls. Serum was separated and exosomes were extracted. The exosomes were identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blot. Subsequently, total RNA was extracted from the purified exosomes for lncRNA transcriptome sequencing. Based on the sequencing results, we identified differentially expressed lncRNAs and mRNAs and conducted multi-dimensional functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database (Reactome), and Disease Ontology (DO). Finally, four key mRNAs (THAP2, ZNF225, MED12, and RNF141) and four differentially expressed lncRNAs (DE-lncRNAs), namely MSTRG.150961.7, ENSG00000273015, MSTRG.336598.1, and ENSG00000273493, were experimentally verified by quantitative real-time polymerase chain reaction (RT-qPCR) technology. Results: Exosomes were successfully isolated from serum and confirmed by particle size, morphological examination, and the expression of exosome-labeled proteins. A total of 2874 DE-lncRNAs were identified, among which 988 were downregulated and 1886 were upregulated. Similarly, 2132 DE-mRNAs were detected, among which 882 were downregulated and 1250 were upregulated. GO analysis revealed significant enrichment in biological processes such as “phospholipid binding”, “phosphatidylinositol binding”, “phosphatase binding”, “phosphatidylinositol bisphosphate binding”, “phosphatidylinositol-4,5-bisphosphate binding”, “phosphatidylinositol-3,5-bisphosphate phosphatase activity”. KEGG is significantly enriched in signaling pathways including “Wnt signaling pathway”, “Hippo signaling pathway”, “Cushing syndrome”, and “Nucleocytoplasmic transport”. The functional annotations of Reactome were significantly enriched in biomolecular pathways including “tRNA processing”, “Cellular response to heat stress”, “Extra-nuclear estrogen signaling”, “Metabolism of non-coding RNA”, and “CTNNB1 T41 mutants aren’t phosphorylated”. DO is significantly enriched in diseases or pathological conditions such as “hepatitis”, “bacterial infectious disease”, “cystic fibrosis”, and “vasculitis”. Conclusions:THAP2, ZNF225, MED12, and RNF141 may serve as potential candidate biomarker for ARHL. Additionally, lncRNA MSTRG.150961.7, lncRNA MSTRG.336598.1, and lncRNA ENSG00000273493 may play significant roles in the pathogenesis of this condition. Full article

Platycladus orientalis exhibits significant potential as an antioxidant, anti-inflammatory, and hair growth-promoting ingredient, while the low bioavailability of raw Platycladus orientalis leaves extracts limits their further application. In this study, yeast fermentation was employed to prepare Platycladus orientalis Leaves Yeast Fermented Solution (PYFS). Its performance on human dermal papilla cells (HDPCs) was systematically investigated. The optimal fermentation strain was screened using the methyl thiazolyl tetrazolium (MTT) assay, and Saccharomycopsis fibuligera CICC33226 (SF) was identified as the most suitable strain for fermentation. The effects of PYFS on the cell cycle distribution, growth factors, inflammatory factors of HDPCs, as well as its hair growth-promoting mechanism, were investigated. Experiments revealed that after fermentation, the proportion of cells in the G0/G1 phase decreased by 11.09%, while the proportion of cells in the S phase increased by 35.44%. Additionally, the level of the growth factor VEGF increased by 42.34%, while the level of the inflammatory factor TGF-β1 decreased by 23.81%. Moreover, the fermentation process correlates with altered mRNA expression of Wnt/β-catenin pathway-related genes by upregulating the mRNA expression levels of β-catenin, DVL1, and LEF1, and downregulating the mRNA expression level of DKK-1. Finally, non-targeted metabolomics technology was used to analyze the metabolite changes after fermentation. The most significant differential metabolites mainly include flavonoids, amino acids and their derivatives, and organic acids and their derivatives. This study utilized microbial fermentation technology to prepare the yeast fermentation solution, selected the optimal fermentation strain, and demonstrated that its fermentation product significantly promotes HDPC metabolic activity, supports hair follicle health by regulating the balance of growth factors, alters expression patterns of Wnt/β-catenin pathway-related genes, and substantially alters the metabolite composition of Platycladus orientalis leaves extract through fermentation. Full article

The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) has been linked to cancer stem cells (CSCs) and telomerase activity; however, the mechanism underlying this association remains unclear. In this study, we engineered dual transcriptional reporters (SORE6-GFP and TERT-BFP) to isolate SOX2⁺OCT4⁺TERT^high subpopulations from AsPC-1 and BxPC-3 cells. We combined Fluorescence-Activated Cell Sorting with functional assays, RNA-seq, and network analysis. Clinically, tumors co-expressing high SOX2/OCT4/TERT levels were associated with reduced overall survival, whereas single-gene elevations were not prognostic. We identified a minority SOX2⁺OCT4⁺TERT^high fraction (~9%) enriched for pluripotency transcripts (SOX2, OCT4, NANOG, and ALDH1A1), which exhibited the highest proliferative, migratory, and invasive capacities. Transcriptomic profiling of SOX2⁺OCT4⁺TERT^high cells showed enrichment of KRAS, telomere maintenance, epithelial–mesenchymal transition, and developmental pathways (WNT and Hedgehog). Connectivity profiling highlighted actionable vulnerabilities, including NF-κB, WNT, and telomerase inhibition pathways. Together, these data define an aggressive telomerase-engaged, pluripotency-driven CSC-like state in PDAC and suggest testable therapeutic strategies that target TERT^high dependencies. Full article

Hemibagrus guttatus is a large omnivorous fish of significant economic value, listed as a Class II protected species in the National Key Protected Wildlife List in 2021 in China. To provide a theoretical foundation for the artificial breeding of H. guttatus, this study employs high-throughput transcriptome sequencing of testes and ovaries to elucidate the molecular regulatory pathways involved in sex differentiation. Because H. guttatus exhibits no obvious sexual dimorphism even during the breeding season, the distinctive contribution of this study compared with previous gonadal-transcriptomic investigations in other Siluriformes lies not only in documenting sex-biased genes but also in providing a molecular foundation for developing non-lethal sex-identification methods for this morphologically indistinguishable species. A total of 303,192,896 raw reads were obtained, with an effective data rate of 98.4%, indicating high sequencing quality. Differential expression analysis identified 8694 genes, including 6369 upregulated in testes and 2325 upregulated in ovaries. Among these, 88 genes were functionally annotated as sex-related, with 62 testis-biased genes such as spata17, sox9, and dmrt1, and 26 ovary-biased genes including cyp19a, wnt8, and sox12. KEGG pathway enrichment analysis revealed that the TGF-β signaling pathway, insulin secretion, and steroid hormone biosynthesis may play crucial roles in gonadal development and differentiation in H. guttatus. The expression patterns of key genes such as hsd11b1, amh, and insl3 were validated by quantitative real-time PCR, showing consistency with the transcriptome results. These findings lay a molecular foundation for understanding the regulatory mechanisms of sex differentiation in H. guttatus, and provide candidate genes for further investigation into the genetic basis of gonadal development, which is essential for improving artificial reproduction and selective breeding practices. Full article

Colorectal cancer (CRC) is a life-threatening malignancy, but our understanding of its pathogenic mechanisms remains incomplete—posing a major constraint on the development of effective therapeutic strategies. The transcription-translation feedback loop of clock genes (e.g., BMAL1, CLOCK, PER1/2/3, and CRY1/2) provides a promising novel avenue for deciphering the initiation and progression of CRC. Mounting evidence indicates that core circadian clock genes play pivotal roles in CRC oncogenesis by orchestrating the regulation of the cell cycle, epithelial–mesenchymal transition (EMT), metabolic reprogramming, and the tumor microenvironment. This review systematically summarizes the expression patterns and mechanistic roles of core clock genes in CRC, while elucidating their molecular underpinnings in tumor progression via key signaling cascades (e.g., Wnt/β-catenin and c-Myc/p21 pathways). We emphasize the associations between circadian disruption and CRC—including diagnostic markers, prognostic assessment, and chemosensitivity—and provide an in-depth discussion of chronotherapeutic strategies and their translational potential. Finally, we identify unaddressed scientific questions and propose future research directions to facilitate the development of novel targeted therapies for CRC. Full article