Biochemistry and Biophysics Reports最新文献

{"title":"Single-cell RNA-seq analysis reveals the multi-step process of cellular senescence","authors":"Minseo Ahn ,&nbsp;Junil Kim ,&nbsp;Jae Ho Seo","doi":"10.1016/j.bbrep.2025.102042","DOIUrl":"10.1016/j.bbrep.2025.102042","url":null,"abstract":"<div><div>Cellular senescence is a phenomenon marked by an irreversible growth arrest with altered physiological properties. Many studies have focused on the characteristics of cells that have already entered a senescent state. However, to elucidate the mechanisms of cellular aging, it is essential to investigate the gradual transition of proliferative cells into senescent cells. We hypothesized that cellular senescence is a complex, multi-step process in which each stage is characterized by distinct cellular features and transcription factor expression patterns. To test this hypothesis, we utilized publicly available single-cell RNA-Seq (scRNA-Seq) data from human umbilical vein endothelial cells (HUVECs) undergoing replicative senescence. We employed Seurat and Monocle 3 to capture the transition from proliferating to senescent states in HUVECs. Four clusters were identified, and each cluster displayed distinct expression patterns of cellular senescence markers and the senescence-associated secretory phenotypes (SASPs). We also employed SCENIC to identify the expression patterns of core transcription factors (TFs) during replicative senescence. While the majority of TFs exhibited a linear trend, HMGB1, FOSL1, SMC3, RAD21, SOX4, and XBP1 showed fluctuating expression patterns during replicative senescence. Furthermore, the expression of these TFs exhibited different patterns in the ionizing radiation (IR) model of senescence. Overall, our study unveils the distinct characteristics of each phase during replicative senescence and identifies expression trends in SASPs and TFs that may play pivotal roles in this process. Unlike previous bulk RNA-seq studies, this work uniquely integrates single-cell trajectory and transcription factor dynamics to decode phase-specific molecular signatures during replicative senescence. Here, we identify key transcription factors potentially involved in senescence induction and provide novel insights into the regulatory complexity of cellular aging.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102042"},"PeriodicalIF":2.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High expression of THY1 is a prognostic marker for gastric Cancer: Deciphering its transcriptional regulation as a component of the Epithelial–mesenchymal transition","authors":"Paulo Rohan,&nbsp;Everton Cruz dos Santos,&nbsp;Pedro Leite Azevedo,&nbsp;Jessica Oliveira da Conceição,&nbsp;Eliana Abdelhay ,&nbsp;Renata Binato","doi":"10.1016/j.bbrep.2025.102050","DOIUrl":"10.1016/j.bbrep.2025.102050","url":null,"abstract":"<div><div>Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with high molecular heterogeneity contributing to its poor prognosis. Among potential biomarkers, <em>THY1</em> is associated with aggressive tumor behavior and poor patient outcomes. However, the transcriptional mechanisms governing <em>THY1</em> expression in GC remain largely unexplored. This study aimed to systematically investigate the upstream regulatory landscape of <em>THY1</em> and its role in tumor progression. By integrating multicohort transcriptomic data (n = 945), we inferred consensus transcriptional regulatory networks (TRNs) and identified six putative transcription factors (PRRX1, TWIST1, SNAI2, MEIS3, VENTX, and EGR2) as robust regulators of <em>THY1</em>. The functional enrichment analysis revealed that these regulators are involved in the epithelial–mesenchymal transition (EMT) and extracellular matrix remodeling, key processes associated with tumor invasion and metastasis. Experimental validation using chromatin immunoprecipitation (ChIP) assays indicated the direct and differential binding of TWIST1 and SNAI2 to the <em>THY1</em> promoter, supporting their roles as key regulators of <em>THY1</em> expression in GC. Our findings provide a mechanistic link between <em>THY1</em> expression and EMT transcriptional programs, offering insights into its association with a poor prognosis. By integrating bioinformatic predictions with experimental demonstration, this study not only improves our understanding of <em>THY1</em> regulation but also provides a framework for dissecting the transcriptional networks governing aggressive tumor phenotypes. These results contribute to a broader understanding of GC progression and may inform future therapeutic strategies targeting EMT-related pathways in <em>THY1</em>^high GC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102050"},"PeriodicalIF":2.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant human Neuritin protects cochlear ribbon synapses and hearing function via ERK1/2 activation post noise-induced injury","authors":"Haiyan Wang ,&nbsp;Jinchi Hu ,&nbsp;Shuangyan Liu ,&nbsp;Fei Gui ,&nbsp;Xiaopin Sun ,&nbsp;Rong Chen ,&nbsp;Guanwu Yin ,&nbsp;Xiaoming Song ,&nbsp;Yi Yang ,&nbsp;Yu Hong","doi":"10.1016/j.bbrep.2025.102044","DOIUrl":"10.1016/j.bbrep.2025.102044","url":null,"abstract":"<div><div>The preservation of synaptic integrity and physiological activity is pivotal for post-traumatic auditory rehabilitation following acoustic overexposure. Neuritin, a neurotrophic factor that facilitates synapse formation, maturation, and enhanced synaptic transmission, is essential for synapse development. In this study, we established a noise-induced cochlear synaptopathy model in CBA/CaJ mice, revealing a temporal association between endogenous Neuritin expression and synaptic density. Furthermore, administration of recombinant Human Neuritin (rhNeuritin) effectively preserves synaptic density in the cochlear basal turn at 7 days and 14 days following noise exposure. Importantly, it preserves the density of functional synapses (represented by overlapping CtBP2 and GluA2 puncta) and synapse function (indicated by ABR I wave amplitudes), thus diminishing the impairment of auditory function. In addition, rhNeuritin reverses the decrease in phosphorylated extracellular signal-regulated protein kinase 1/2 (<em>p</em>-ERK1/2) levels resulting from noise exposure. By primarily preserving both the number and functionality of synapses in the basal turn, potentially via the induction of ERK1/2 phosphorylation, rhNeuritin mitigated hearing loss. These findings underscore the protective efficacy of rhNeuritin against noise-induced synaptic injury.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102044"},"PeriodicalIF":2.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short communication: The effect of Propolis extract treatment on the Lee index and brain-body weight ratio in diet-induced obesity rats","authors":"Andreas Christoper ,&nbsp;Herry Herman ,&nbsp;Rizky Abdulah ,&nbsp;Felix Zulhendri ,&nbsp;Ronny Lesmana","doi":"10.1016/j.bbrep.2025.102039","DOIUrl":"10.1016/j.bbrep.2025.102039","url":null,"abstract":"<div><div>Obesity is a severe public health concern that can impair brain structure and function. The potential anti-inflammatory and anti-obesogenic properties of propolis extract are beneficial in preventing brain damage after diet-induced obesity. The purpose of the study is to investigate the role of propolis extract in high-fat diet-induced obesity rats using the Lee index and brain-body weight ratio (BBWR). We divided the rats into the experimental groups as follows: CD (normal chow diet), CP (normal chow diet with propolis treatment), FD (high-fat diet), and FP (high-fat diet with propolis treatment). We administered propolis extract in CP and FP for nine weeks during 21 weeks of diet. The rat's body weight and length were measured for obesity evaluation. The brain of all experimental rats was harvested and weighed at the end of the study. We found that a chronic high-fat diet significantly increased body weight and the Lee index (<em>p</em> &lt; 0.01). However, a high-fat diet significantly decreased brain weight and BBWR in rats (<em>p</em> &lt; 0.05). Nine weeks of propolis extract supplementation in the FP group reduced the Lee index (<em>p</em> &lt; 0.01) and slightly increased brain weight and BBWR compared to the FD group. We observed a negative correlation between brain weight and the Lee index (R = – 0.64). Therefore, we conclude that propolis extract has the potential to sustain brain health in obesity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102039"},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paridis Rhizoma Saponins ameliorate CCl4-induced liver fibrosis via modulation of the Nrf2-HO-1/NQO-1 and TGF-β1/Smads signaling pathways","authors":"Yan Hong ,&nbsp;Shuang Geng ,&nbsp;Huihao Ao ,&nbsp;Mengya Fu ,&nbsp;Xiaojun Yang ,&nbsp;Gang Cao ,&nbsp;Yanquan Han","doi":"10.1016/j.bbrep.2025.102040","DOIUrl":"10.1016/j.bbrep.2025.102040","url":null,"abstract":"<div><h3>Objective/background</h3><div>Paridis Rhizoma is a common traditional Chinese medicine (TCM), possessing therapeutic effects including heat-clearing, detoxification, and liver calming effects. It is frequently applied in TCM prescriptions for the treatment of liver disease. Studies have shown that total saponins derived from Paridis Rhizoma (PRS) have potent anti-liver fibrosis effect, but its mechanism in treating liver fibrosis has not been clarified. This study aimed to explore the therapeutic effect of PRS on liver fibrosis and elucidate their potential underlying pharmacological mechanisms.</div></div><div><h3>Methods</h3><div>The targets and pathways of Paridis Rhizoma Saponins on experimental liver fibrosis were analyzed using network pharmacology and molecular docking. PRS was administered to rats with CCL₄-induced liver fibrosis rats. Liver function, fibrosis, and inflammatory indicators were assessed using ELISA to measure serum AST and ALT, as well as liver tissue levels of HA, LN, Col IV, and PC-III fibrosis markers. Additionally, inflammatory markers IL-6, IL-β, and TNF-a were quantified. Liver morphological, H&amp;E, and Masson's staining were used to observe the degree of liver fibrosis. The mRNA and protein expressions of Nrf2-HO-1/NQO-1 and TGF-β1/Smads signaling pathways in liver tissues were detected using immunohistochemistry (IHC) staining, Western blot (WB), and RT-qPCR.</div></div><div><h3>Results</h3><div>Comprehensive network pharmacology and animal experiments show that PRS may act on STAT3, SRC, VEGFA, AKT1 and other targets through its polyphyllin I, polyphyllin II, polyphyllin VI, polyphyllin VII and other components.Analysis from ELISA showed that PRS could improve liver function, mitigate the progression of liver fibrosis, and regulate inflammatory responses in rats. Morphological, H&amp;E, and Masson's staining demonstrated that PRS significantly improved liver tissue immune response and necrosis. Additionally, IHC staining, WB results, and RT-qPCR results showed that PRS positively regulates the Nrf2-HO-1/NQO-1 and TGF-β1/Smads signaling pathways to counteract the development of pathological liver fibrosis in rats.</div></div><div><h3>Conclusion</h3><div>These findings indicate that PRS can mitigate the impact of CCl₄-induced liver fibrosis in experimental animals by upregulating the Nrf2-HO-1/NQO-1 and downregulating the TGF-β1/Smads signaling pathways.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102040"},"PeriodicalIF":2.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid hormone binding and modulation of Trichinella spiralis progesterone receptor: A computational approach","authors":"Muhammad Tahir Aleem ,&nbsp;Shakeel Ahmed Lakho ,&nbsp;Muhammad Mohsin ,&nbsp;Shahbaz Ul haq ,&nbsp;Ashiq Ali ,&nbsp;Danmei Huang ,&nbsp;Fenfei Gao","doi":"10.1016/j.bbrep.2025.102031","DOIUrl":"10.1016/j.bbrep.2025.102031","url":null,"abstract":"<div><div>Trichinellosis, caused by <em>Trichinella</em> species, including <em>Trichinella spiralis</em>, is a foodborne zoonotic disease. Upon ingestion, ML swiftly invade the intra-multicellular niche of the small intestine, undergoing four rapid molts to mature into adults. In general, the route of transmission for <em>T. spiralis</em> nematodes occurs through ingestion of pork. Therefore, it is crucial to develop a vaccine that can deal with trichinellosis, particularly for humans and pigs. In this study, homology modelling, molecular docking, simulations and molecular mechanics-based scoring (MM/GBSA) are used to investigate the interaction between <em>T. spiralis</em> membrane-associated progesterone receptor component 2 (<em>Ts</em>-MAPRC2) and different steroids hormones. In the most favorable region, 93 amino acid residues (92.1 %) are located, while 7 amino acids (6.9 %) are located in the allowed region, showing that the model with a 93.33 ERRAT quality factor is good quality. The MD simulations were conducted for 50 ns to explore the affinities and stability of four hormones chosen from the docking studies that showed similar binding poses to the control hormone Mifepristone. Simulations showed that the selected hormones were potent Ts-MAPRC2 binders and can act as leads to determine their activity by biophysical assays. Discovery of these five steroid hormones and interactions with Ts-MAPRC2 could lead to new therapies and vaccines for trichinellosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102031"},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8","authors":"Jianan Zhao ,&nbsp;Yunshen Li ,&nbsp;Runrun Zhang ,&nbsp;Yu Shan ,&nbsp;Chenyang Song ,&nbsp;Yaxin Cheng ,&nbsp;Yiming Shi ,&nbsp;Yixin Zheng ,&nbsp;Fuyu Zhao ,&nbsp;Junyu Fan ,&nbsp;Cen Chang ,&nbsp;Yuejuan Zheng ,&nbsp;Dongyi He","doi":"10.1016/j.bbrep.2025.102038","DOIUrl":"10.1016/j.bbrep.2025.102038","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates therapeutic gene targets and their epigenetic modifications in rheumatoid arthritis (RA), focusing on the molecular effects of methotrexate (MTX), Janus kinase (JAK) inhibitors, and (5R)-5-hydroxytriptolide (LLDT-8) on fibroblast-like synoviocytes (FLS).</div></div><div><h3>Methods</h3><div>Primary FLS were isolated from synovial tissues of RA and osteoarthritis (OA) patients and treated with MTX, JAK inhibitors, and LLDT-8. RNA sequencing identified differentially expressed genes (DEGs) under each treatment. The intersection of differentially expressed genes with trend analysis identified as potential drug target genes. Functional enrichment analyses were performed to explore associated pathways. Methylation changes in key genes were examined using the GEO database (GSE46364), and clinical relevance was evaluated using RA patient data from the PEAC database.</div></div><div><h3>Results</h3><div>Compared to the osteoarthritis FLS group, the RA FLS group showed significant differences in 5095 genes (3300 upregulated and 1795 downregulated). After JAK inhibitor treatment, 3795 significant differential genes were identified in RA FLS (1733 upregulated and 2062 downregulated). MTX treatment resulted in 3195 significant differential genes (2171 upregulated and 1023 downregulated), while LLDT-8 treatment revealed 12,993 significant differential genes (7801 upregulated and 5192 downregulated). Following trend analysis and de-duplication, we identified 45 important drug target genes that exhibited significant correlations with common clinical indices in RA patients. Among these, <em>GALNT9</em> and <em>CCNF</em> showed notable alterations in both methylation and expression levels, suggesting potential roles in RA pathogenesis and drug response. Functional enrichment highlighted critical pathways, including cell cycle, FoxO, and p53 signaling, which are implicated in FLS regulation and RA progression.</div></div><div><h3>Conclusion</h3><div>This study highlights therapeutic gene targets and their epigenetic modifications as potential mechanisms underlying the effects of MTX, JAK inhibitors, and LLDT-8 in RA treatment. <em>GALNT9</em> and <em>CCNF</em> emerge as promising candidates for further exploration in targeted therapeutic strategies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102038"},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine intestinal organoids cultured in an organ-on-a-chip microphysiological system","authors":"James Bacon,&nbsp;Halie Kitchel,&nbsp;John Stutz,&nbsp;Jack Hua Chen,&nbsp;Aaron Smith,&nbsp;Robert D. Van Horn,&nbsp;Christopher Moreland,&nbsp;Trent Abraham,&nbsp;Thomas Baker ,&nbsp;Eitaro Aihara,&nbsp;Kathleen Hillgren","doi":"10.1016/j.bbrep.2025.102036","DOIUrl":"10.1016/j.bbrep.2025.102036","url":null,"abstract":"<div><div>Preclinical studies are a vital component of pharmaceutical development and improvements in the predictive value of in vitro studies are essential. Organ-on-a-chip in vitro models are a recent advancement in the pursuit of improved reproduction of in vivo tissue complexity. Here, we report the development and characterization of porcine intestinal cells from organoids on chips with microfluid dynamics and peristaltic-like strain in a microphysiological system. Intestinal epithelial cells were grown on a porous membrane as a co-culture with human intestinal microvascular endothelial cells for up to 12 days. These cultures formed villi-like structures and established a tight barrier replete with F-actin and tight junctions. A demarcated region of the epithelial cells was in an actively proliferative stage, reminiscent of intestinal crypts. The intestinal epithelial cell growth was characterized for the presence of enterocytes, goblet cells and enteroendocrine cells. Notable drug transporters and CYP450 metabolic activity were present in these cultures. The organoid chip maintained barrier function as the paracellular permeability was low. In contrast, the permeability enhancer, sodium caprate (C₁₀), increased the apparent permeability of molecular weight marker compounds by 2- to 3-fold, and upon removal of C₁₀, the barrier was shown to be recovered. The porcine intestinal chip represents a new in vitro model with potential application in multiple aspects of pharmaceutical testing including drug metabolism, drug transporters and safety.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102036"},"PeriodicalIF":2.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting effects of acute versus chronic intermittent hypoxia on leptin secretion in differentiated human adipocytes – Implications for sleep apnea","authors":"Kiran R. Somers ,&nbsp;Christiane Becari ,&nbsp;Katarzyna Polonis ,&nbsp;Prachi Singh","doi":"10.1016/j.bbrep.2025.102030","DOIUrl":"10.1016/j.bbrep.2025.102030","url":null,"abstract":"<div><div>Obstructive sleep apnea (OSA) is a common sleep disorder associated with repetitive episodes of nocturnal intermittent hypoxia (IH), obesity and elevated leptin. Newly diagnosed OSA patients have a history of significant recent weight gain. While IH is implicated in OSA pathophysiology, the factors contributing to weight gain in OSA are not completely understood. Leptin is an adipokine with a central role in energy homeostasis and appetite control. Increases in leptin suppress appetite, while decreases in leptin increase appetite and may consequently cause weight gain. Using an <em>in vitro</em> approach, we examined the role of acute and chronic IH exposure on leptin secretion in differentiated human white preadipocytes. We show that acute 24-h exposure to IH and sustained hypoxia both increased leptin secretion, compared to normoxic controls (p = 0.01). In contrast, chronic repetitive IH exposure for 7 days decreased leptin secretion, compared to normoxic controls (p = 0.02). The decrease in leptin secretion during chronic IH exposure suggests a mechanism which may contribute to increased appetite and thereby predispose patients with untreated OSA to weight gain and obesity in early stages. As obesity progresses, leptin levels likely rise secondary to the increase in body fat. Elevated leptin levels in patients with longstanding OSA may be indicative of increased fat mass and not a consequence of IH-mediated effects on adipocytes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102030"},"PeriodicalIF":2.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes mellitus – conventional therapies and future perspectives in innovative treatment","authors":"Barbara Gieroba,&nbsp;Adrianna Kryska,&nbsp;Anna Sroka-Bartnicka","doi":"10.1016/j.bbrep.2025.102037","DOIUrl":"10.1016/j.bbrep.2025.102037","url":null,"abstract":"<div><div>Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and dysfunction of the pancreatic beta cells, which leads to elevated blood glucose levels. Conventional therapies, including metformin, sulfonylureas, and insulin, have long served as the cornerstone of treatment. However, they often face limitations, such as adverse effects, reduced efficacy over time, and difficulties in achieving optimal glycemic control. This has sparked considerable interest in developing novel and experimental therapeutic strategies to enhance treatment outcomes. Recent advances in diabetes management feature dual incretin receptor agonists, like tirzepatide, which combine GLP-1 and GIP receptor agonism, resulting in increased insulin secretion, decreased glucagon release, and significant weight loss. Additionally, dual SGLT1/2 inhibitors, such as sotagliflozin, show promise for more significant blood glucose reduction and improved weight loss by targeting glucose regulation in both the gut and kidneys. Other promising methods include glucagon receptor antagonists, GPR119 agonists, and FGF21 analogs, which strive to enhance insulin sensitivity and improve glucose metabolism through innovative pathways. Gene editing technologies, including CRISPR-Cas9 and AMPK activators, are also being investigated to tackle the underlying pathophysiology of T2DM more effectively. While these experimental therapies show promise, their long-term safety and efficacy remain under research. This article reviews the conventional therapies currently in use. It investigates future perspectives on innovative treatments for T2DM, emphasizing the potential of these new therapies to transform diabetes care and enhance patient outcomes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102037"},"PeriodicalIF":2.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}