Search Results (35)

Exercise-induced myokines have emerged as crucial mediators of the beneficial effects of physical activity on neurodegenerative diseases through complex molecular mechanisms involving oxidative stress reduction, neuroinflammation suppression, and synaptic plasticity enhancement. Among these myokines, irisin, encoded by the FNDC5 gene, has gained significant attention as a potential therapeutic target in neurodegenerative conditions due to its ability to cross the blood–brain barrier and exert pleiotropic neuroprotective effects. This review synthesizes current evidence from both preclinical and clinical studies examining the role of exercise-induced irisin in neurodegeneration, with particular emphasis on translational potential and therapeutic applications. A comprehensive search was conducted across PubMed, Web of Science, Scopus, and EMBASE databases (spanning January 2015 to December 2024) to identify peer-reviewed articles investigating irisin’s neuroprotective mechanisms in neurodegenerative diseases. Ten studies met the inclusion criteria (five rodent/primate model studies and five human clinical investigations), which were analyzed for methodological rigor, intervention protocols, biomarker quantification methods, and reported outcomes. Reviewed studies consistently demonstrated that exercise-induced endogenous irisin elevation correlates with improved cognitive function, reduced neuroinflammatory markers, enhanced synaptic plasticity, and modulation of neurodegenerative pathways, with exogenous irisin administration reproducing several neuroprotective benefits observed with exercise training in animal models. However, substantial heterogeneity exists regarding exercise prescription parameters (intensity, duration, frequency, modality), training-induced irisin quantification methodologies (ELISA versus mass spectrometry), and study designs (ranging from uncontrolled human observations to randomized controlled trials in animal models). Critical appraisal reveals that human studies lack adequate control for confounding variables including baseline physical fitness, comorbidities, concurrent medications, and potential sources of bias, while biochemical studies indicate distinct pharmacokinetics between endogenous training-induced irisin and exogenous bolus dosing, necessitating careful interpretation of therapeutic applicability. The translational potential of irisin as a therapeutic agent or drug target depends on resolving methodological standardization in biomarker measurement, conducting well-designed clinical trials with rigorous control for confounders, and integrating findings from molecular/biochemical studies to elucidate mechanisms linking irisin to disease modification. Future research should prioritize establishing clinical trial frameworks that harmonize exercise prescriptions, employ robust biomarker quantification (mass spectrometry), and stratify participants based on disease stage, comorbidities, and genetic predisposition to clarify irisin’s role as a potential therapeutic intervention in neurodegenerative disease management. Full article

Irisin is a myokine secreted by muscle in response to exercise. It is derived from a transmembrane protein called fibronectin type III domain-containing protein 5 (FNDC5). The Fndc5 gene is expressed in several tissues, including skeletal muscle, brain, adipose tissue, heart, kidney, and lung. Irisin is cleaved from FNDC5 protein by the enzyme furin and released into circulation. In addition to exercise, several drugs have been shown to increase the production of irisin. Administration of exogenous irisin mimics the beneficial actions of exercise. Irisin can cross the blood–brain barrier and exert neuroprotective actions in the brain. It has been shown to reverse Alzheimer’s pathologies in clinical and animal studies. Irisin also exerts protective effects against obesity, diabetes, and cardiovascular disease, diseases that often coexist with aging AD patients. Multiple approaches have been taken to suggest that exercise may act through irisin. Studies have provided direct evidence linking the two using Fndc5 gene deletion and irisin antibodies. Irisin binds to αVβ1/β5 integrins to mediate the activation of integrin-FAK pathways. While exercise as a lifestyle modification for healthy aging is well recognized, it may present limitations in some aging populations, especially those with disease conditions, including Parkinson’s disease. Administration of exogenous irisin or small molecules that increase the expression of endogenous irisin or facilitate its actions are some alternate approaches that can mimic the beneficial actions of exercise. This review discusses the therapeutic potential of irisin in the treatment of neurodegenerative and other aging-associated diseases. Full article

Iron plays a key role in oxygen transport, hematopoiesis, and hypoxia adaptation. This study aimed to explore the dynamic response mechanism of the iron regulatory network and key genes in Duroc piglets. Eighteen weaned piglets were randomly divided into three dietary intervention groups: low iron (0 mg/kg), conventional (100 mg/kg), and high iron (200 mg/kg). Transcriptomics technology was used to screen key liver iron regulatory genes under the influence of different dietary iron concentrations, and the expression of related genes was verified using primary pig liver cells. Fasting serum iron metabolism parameters were detected and iron content in organs was quantified. The results show, enrichment analysis highlighted immune–metabolic signaling, including NF-κB, PI3K-Akt, and TGF-β, and a total of 14 candidate genes (such as FGF21, SAA2/3, FNDC1, ETNPPL, TFR1) were identified. The study observed that these genes showed obvious dosage differentiation and nonlinear patterns. However, findings reflect mRNA-level changes and GO/KEGG over-representation, protein-level validation is planned in follow-up studies. Through the integration of in vitro and in vivo data, this study discovered new liver genes that may be related to pig iron homeostasis function, providing a theoretical basis for analyzing the regulatory mechanism of piglet iron response. Full article

Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy—processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases. Full article

Goats are widely recognized for their adaptability and resource efficiency, making them an excellent choice for sustainable farming. However, the Hainan Black goat (HNBG), a vital breed in southern China’s tropical regions, faces significant challenges that threaten its productivity and economic viability. Specifically, young HNBGs exhibit stunted growth and poor muscle development, indicating the breed may have more genetic defects that cause the poor phenotypes. The FNDC5 gene, which encodes the protein irisin, plays a key role in promoting mitochondrial biogenesis and oxidative metabolism by activating critical signaling molecules such as PGC-1α, thereby enhancing muscle endurance and metabolic efficiency. This study aimed to investigate the impact of missense mutations in the FNDC5 gene on growth and meat quality traits in HNBGs. We sequenced a population of HNBGs and identified three SNPs that could lead to amino acid substitutions. Notably, SNP1 (p.119A/V) and SNP2 (p.135R/H) showed strong linkage. Predictions on the structural effects of these mutations indicated that SNP1 (p.119A/V) and SNP3 (p.170W/G) could alter the secondary structure of the FNDC5 protein. Association analyses revealed that SNP1 (p.119A/V) and SNP2 (p.135R/H) were significantly associated with morphometric traits and meat quality. The phenotypic values of SNP1 and SNP2 co-mutants were significantly lower than those of other combined genotypes. Furthermore, gene expression levels of FNDC5 varied notably across individuals with different SNP1 genotypes. These findings suggest that FNDC5-SNP1 (p.119A/V) could serve as a promising genetic marker for selecting HNBGs with improved growth and muscle development, offering a potential pathway for enhancing key economic traits in this breed. Full article

Metastasis is a leading cause of lung adenocarcinoma (LUAD)-related mortality and presents significant challenges for treatment. The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor (GPCR) family, has an unclear role in LUAD progression. This study aimed to investigate the function and underlying mechanisms of GRPR in LUAD metastasis. Our findings revealed that GRPR levels were significantly elevated in tumor tissues, and higher GRPR expression was associated with worse overall survival outcomes. Functional assays demonstrated that GRPR overexpression enhanced LUAD cell invasion, while GRPR knockdown inhibited invasion both in vitro and in vivo. RNA sequencing and gene set enrichment analysis (GSEA) identified an enrichment of metastasis-promoting genes in GRPR-overexpressing cells, with CRABP2 and FNDC4 emerging as key targets. Clinical analyses further confirmed a positive correlation between GRPR expression and the levels of CRABP2 and FNDC4 in LUAD patients. These results suggest that GRPR could serve as both a prognostic marker and a therapeutic target to inhibit metastasis in LUAD. Full article

Recurrent Pregnancy Loss (RPL), also named Recurrent Spontaneous Abortion (RSA), is a common fertility problem that refers to at least two consecutive pregnancy losses and affects 1–2% of couples all over the world. Despite common causes such as genetic abnormalities, uterine anomalies or hormonal and metabolic disorders, there is still a huge challenge in identifying the causes of about 40–60% of RPL patients. Circular RNAs (circRNAs) are endogenous ncRNAs with a unique closed-loop and single-stranded structure. Accumulated evidence indicates the role of circRNAs in embryonic development and implantation, which may help decipher the mechanisms and causes underlying RSA. Four works were selected in the SRA public repository that used RNAseq analysis in control and RPL samples in four tissues: endometrium, chorionic villus tissue, decidua and decidua immune cells. Two programs were selected for circRNA detection: DCC and CIRI2. A total of 1715 candidate circRNAs were detected after filtering the results. In the differential expression analysis, decidual tissue showed the highest percentage of circRNA with differential expression between cases and controls. CircRNAs originating from genes OGA, FNDC3B, RAB11FIP1, SIPA1L2 and GREB1L showed the highest expression in women suffering from pregnancy losses, in decidual tissue or endometrium. In the GO term enrichment analysis, multiple terms related to embryonic development and immunological response were consistently enriched in villus and decidual tissues. Although some differentially expressed circRNAs were shared between tissues, decidua seems the tissue of choice for analyzing the role of circRNAs in RPL. Full article

Spinibarbus sinensis, also known as Qingbo, is an important economic fish in China. However, the detailed mechanisms underlying its growth are still unknown. To excavate the genes and signaling pathways related to its growth, we compared the transcriptome profiles of the hepatopancreas tissues of S. sinensis, with two groups of growth rate for evaluation. An average of 66,304,909 and 68,739,585 clean reads were obtained in the fast growth (FG) and slow growth (SG) group, respectively. The differential gene expression analysis results showed that 272 differentially expressed genes (DEGs) were screened between the FG and SG groups, including 101 up-regulated genes and 171 down-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that GO terms related to metabolic process, organic substance metabolic process, and catalytic activity were enriched, pathway signals related to steroid biosynthesis and protein digestion and absorption were also detected. Meanwhile, the potential key regulatory genes sst2, fndc4, and cckra related to the growth of S. sinensis were screened. Reverse transcript fluorescence quantitative PCR (RT-qPCR) validation of 18 DEGs associated with growth differences showed that the RT-qPCR results were consistent with RNA-seq analysis, and nine genes, stk31, gpr149, angptl1, fstl1, sik1, ror2, nlrc3, pdlim2, and nav2 were significantly expressed in the FG group. bmp1, stc1, gpatch8, sstrt2, s100a1, ktf6, cckar6, sync1, bhlha15, a total of nine genes were significantly expressed in the SG group. This study provides basic information for improving the growth characteristics of S. sinensis and the functional research of candidate genes. Full article

Campylobacter jejuni is a zoonotic bacterium with the capacity to invade the epithelial cells during the pathogenic process. Several bacterial factors have been identified to contribute to this process, but our knowledge is still very limited about the response of the host. To reveal the major routes of this response, a whole-transcriptome analysis (WTA) was performed where gene expressions were compared between the 1st and the 3rd hours of internalization in INT407 epithelial cells. From the 41,769 human genes tested, altogether, 19,060 genes were shown through WTA to be influenced to different extents. The genes and regulation factors of transcription (296/1052; 28%), signal transduction (215/1052; 21%), apoptosis (153/1052; 15%), immune responses (97/1052; 9%), transmembrane transport (64/1052; 6%), cell–cell signaling (32/1052; 3%), cell–cell adhesions (29/1052; 3%), and carbohydrate metabolism (28/1052; 3%) were the most affected biological functions. A striking feature of the gene expression of this stage of the internalization process is the activation of both immune functions and apoptosis, which convincingly outlines that the invaded cell faces a choice between death and survival. The seemingly balanced status quo between the invader and the host is the result of a complex process that also affects genes known to be associated with postinfectious pathological conditions. The upregulation of TLR3 (3.79×) and CD36 (2.73×), two general tumor markers, and SERPINEB9 (11.37×), FNDC1 (7.58×), and TACR2 (8.84×), three factors of tumorigenesis, confirms the wider pathological significance of this bacterium. Full article

Sarcopenia, defined as the age-associated loss of muscle mass and increased fragility with age, is increasing worldwide. The condition often precedes the development of Alzheimer’s disease, thereby decreasing the levels of mobility and physical activity in those affected. Indeed, the loss of muscle mass has, in some studies, been associated with an increased risk of Alzheimer’s disease and other dementias. However, a detailed understanding of the interplay between both conditions is not available and needs to be thoroughly addressed. In the following review, we focus on several genes, specifically APOE, BDNF, ACE, FTO, and FNDC5, that have been associated with both conditions. We also discuss the epigenetic regulation of each of these genes along with non-coding RNAs (ncRNAs) that may have a role in the development of both the sarcopenic and Alzheimer’s disease phenotypes. Finally, we assert that the application of systems biology will unravel the relationship between sarcopenia and Alzheimer’s disease and believe that the prevention of muscle loss in older age will reduce the incidence of debilitating cognitive decline. Full article

Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand–receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour. Full article

Background: Tongue squamous cell carcinoma (TSCC) represents one of the major subsets of head and neck cancer, which is characterized by unfavorable prognosis, frequent lymph node metastasis, and high mortality rate. The molecular events regulating tongue tumorigenesis remain elusive. In this study, we aimed to identify and evaluate immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in TSCC. Methods: The lncRNA expression data for TSCC were obtained from The Cancer Genome Atlas (TCGA) and the immune-related genes were downloaded from the Immunology Database and Analysis Portal (ImmPort). Pearson correlation analysis was performed to identify immune-related lncRNAs. The TCGA TSCC patient cohort was randomly divided into training and testing cohorts. In the training cohort, univariate and multivariate Cox regression analyses were used to determining key immune-related lncRNAs, which were then validated through Cox regression analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) analysis in the testing cohort. Results: Six immune-related signature lncRNAs (MIR4713HG, AC104088.1, LINC00534, NAALADL2-AS2, AC083967.1, FNDC1-IT1) were found to have prognostic value in TSCC. Multivariate and univariate cox regression analyses showed that the risk score based on our six-lncRNA model, when compared to other clinicopathological factors (age, gender, stage, N, T), was an important indicator of survival rate. In addition, Kaplan–Meier survival analysis demonstrated significantly higher overall survival in the low-risk patient group than the high-risk patient group within both training and testing cohorts. The ROC analysis indicated that the AUCs for 5-year overall survival were 0.790, 0.691, and 0.721, respectively, for training, testing, and entire cohorts. Finally, PCA analysis demonstrated that the high-risk and low-risk patient groups presented significant deviation regarding their immune status. Conclusions: A prognostic model based on six immune-related signature lncRNAs was established. This six-lncRNA prognostic model has clinical significance and may be helpful in the development of personalized immunotherapy strategies. Full article

Severe obesity (SO) can accelerate atherosclerosis and the onset of acute cardiovascular events. The diagnosis of atherosclerosis in the context of a high body mass index (BMI) can be challenging, making the identification of biomarkers clinically relevant. We aimed to assess the usefulness of irisin as a biomarker for subclinical atherosclerosis in participants with SO. This prospective observational study included 61 participants undergoing bariatric surgery for SO, defined as a BMI >40 kg/m² or >35 kg/m² with at least one comorbidity. Atherosclerotic plaques were detected by ultrasound. Plasma samples were obtained 1 month before and at 6 and 12 months after bariatric surgery to measure irisin by ELISA. Additionally, subcutaneous samples of adipose tissue were taken and genotyped to identify irisin polymorphism rs3480. Irisin levels were positively correlated with BMI (r = 0.23, p = 0.0064), negatively correlated with atheroma-related parameters (e.g., carotid intima-media thickness), and lower in subjects with atheroma (p < 0.0002). Irisin also showed good overall accuracy for discriminating plaque presence (AUC, 0.81; 95% CI, 0.6956–0.9156). However, the rs3480 polymorphism correlated with neither the irisin levels nor the presence of atheromas. Iirisin could identify subclinical atherosclerosis in SO and might facilitate clinical diagnosis. Full article

Obesity is associated with excessive fat accumulation in adipose tissue and other organs, such as skeletal muscle, whereas aerobic exercise (AE) plays an important role in managing obesity through profound protein regulation. Our study aimed to investigate the impact of AE on proteomic changes in both the skeletal muscle and the epididymal fat pad (EFP) of high-fat-diet-induced obese mice. Bioinformatic analyses were performed on differentially regulated proteins using gene ontology enrichment analysis and ingenuity pathway analysis. Eight weeks of AE significantly reduced body weight, increased the serum FNDC5 level, and improved the homeostatic model assessment of insulin resistance. A high-fat diet caused alterations in a subset of proteins involved in the sirtuin signaling pathway and the production of reactive oxygen species in both skeletal muscle and EFP, leading to insulin resistance, mitochondrial dysfunction, and inflammation. On the other hand, AE upregulated skeletal muscle proteins (NDUFB5, NDUFS2, NDUFS7, ETFD, FRDA, and MKNK1) that enhance mitochondrial function and insulin sensitivity. Additionally, the upregulation of LDHC and PRKACA and the downregulation of CTBP1 in EFP can promote the browning of white adipose tissue with the involvement of FNDC5/irisin in the canonical pathway. Our study provides insights into AE-induced molecular responses and may help further develop exercise-mimicking therapeutic targets. Full article

Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55–MAP3K1 genes were previously reported to exhibit genome-wide significance in primary open-angle glaucoma (POAG). Since these polymorphisms have not been investigated in the Arab population of Saudi Arabia, we examined their association with POAG in a Saudi cohort. Genotyping was performed in 152 POAG cases and 246 controls using Taqman real-time assays and their associations with POAG and clinical markers, such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications, were tested by statistical methods. There was no association observed between POAG and the minor allele frequencies of rs2472493[G], rs7636836[T], or rs61275591[A]. None of the genetic models such as co-dominant, dominant, recessive, over-dominant, and log-additive demonstrated any genotype link. The Rs2472493 genotype showed a modest association (p = 0.044) with the number of antiglaucoma medications in the POAG group, but no significant genotype effect on post hoc analysis. In addition, a G-T allelic haplotype of rs2472493 (ABCA1) and rs7636836 (FNDC3B) did show an over two-fold increased risk of POAG (odds ratio = 2.18), albeit non-significantly (p = 0.092). Similarly, no other allelic haplotype of the three variants showed any significant association with POAG. Our study did not replicate the genetic association of rs2472493 (ABCA1), rs763683 (FNDC3B), and rs61275591 (ANKRD55–MAP3K1) in POAG and related clinical phenotypes, suggesting that these polymorphisms are not associated with POAG in a Saudi cohort of Arab ethnicity. However, large population-based multicenter studies are needed to validate these results. Full article