Biochemistry and Biophysics Reports最新文献

{"title":"Two-pore domain potassium channel TREK-1 contributes to arachidonic acid-induced Ca2+ signaling in human fibroblast-like synovial cells","authors":"Battulga Khaltar ,&nbsp;Futoshi Toyoda ,&nbsp;Kosuke Kumagai ,&nbsp;Takafumi Yayama ,&nbsp;Batchimeg Tsedenbal ,&nbsp;Kohei Umeda ,&nbsp;Hideki Saito ,&nbsp;Naranbat Lkhagvasuren ,&nbsp;Mitsuhiko Kubo ,&nbsp;Shinji Imai","doi":"10.1016/j.bbrep.2025.102098","DOIUrl":"10.1016/j.bbrep.2025.102098","url":null,"abstract":"<div><div>Human fibroblast-like synovial cells (hFLSs) are essential in maintaining the structural integrity of the articular cartilage and promoting joint inflammation. These cells are highly responsive to various physical and chemical stimuli, many of which influence cellular processes through intracellular Ca²⁺ signaling and membrane ion channel activity. In this study, we investigated the role of the TREK-1 two-pore domain potassium (K2P) channel as a molecular sensor of arachidonic acid (AA) in FLSs. Patch-clamp recordings revealed an outwardly rectifying K⁺ conductance resistant to conventional K⁺ channel blockers (4-AP and TEA) but sensitive to inhibition by quinidine, a broad-spectrum K2P blocker. Activation of the TREK-1 channel with 4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB) and ML402 increased this current, and immunocytochemical staining demonstrated TREK-1 expression in hFLSs. AA exposure potentiated the K⁺ current in a concentration-dependent manner and caused hyperpolarization of the resting membrane potential, effects fully antagonized by pretreatment of the cells with spadin, a TREK-1 selective blocker. Fluorescent Ca²⁺ measurements showed that AA-induced variable increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in different FLSs, and spadin attenuated these responses, reducing the number of cells exhibiting oscillatory and sustained [Ca²⁺]_i elevations. In a nominally Ca²⁺-free medium, spadin had no effect, suggesting that TREK-1 channels regulate plasma membrane Ca²⁺ influx. Our findings provide the first electrophysiological and pharmacological evidence for the involvement of TREK-1 channels in AA-induced Ca²⁺ signaling in hFLSs.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102098"},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364608","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":"KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study","authors":"Shayan Marhamati ,&nbsp;Morvarid Hamrahjoo ,&nbsp;Zeinab Seyedkhan ,&nbsp;Mahdi Bahmani ,&nbsp;Nasrin Ziamajidi ,&nbsp;Iraj Khodadadi ,&nbsp;Mohadese Pouryani ,&nbsp;Roghayeh Abbasalipourkabir","doi":"10.1016/j.bbrep.2025.102095","DOIUrl":"10.1016/j.bbrep.2025.102095","url":null,"abstract":"<div><div>Esophageal cancer (EC) is the eighth most common cancer in the world. Due to poor survival rates and severe side effects of current therapies, there is a need for a better understanding of the mechanisms and signaling pathways involved in EC. In this study, we downloaded the microarray datasets GSE157808 and GSE92396 from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R software and validated through the GEPIA and TIMER databases. CytoHubba was used to extract hub genes from the overlapping DEGs. The TIMER database was employed to assess correlations between gene expression and immune infiltration. Additionally, hub gene expression was analyzed in 20 pairs of EC tissue samples through RT-qPCR and Western blot. We evaluated clinicopathological correlations and diagnostic potential. We identified 83 overlapping DEGs across the datasets. Subsequently, based on the highest number of degrees in the hub gene network, the <em>KRT6A, KRT6B, PKP1</em>, and <em>PKP3</em> genes were selected for further experimental analysis. EC samples showed upregulated expression of these genes, consistent with our bioinformatic analysis and the GEPIA and TIMER databases. However, KRT6B protein levels were not significantly elevated. <em>KRT6A</em> expression was associated with lymph node metastasis, while <em>KRT6B</em> showed an inverse relationship with necrosis. Gene expression levels correlated with components of immune infiltration. ROC analysis indicated possible diagnostic value, while Kaplan-Meier plots showed no significant association with survival outcomes. Elevated expression of <em>KRT6A</em>, <em>KRT6B</em>, <em>PKP1</em>, and <em>PKP3</em> is associated with EC, indicating their potential as candidates for further investigation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102095"},"PeriodicalIF":2.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335774","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":"Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a Ca2+-dependent mechanism","authors":"Samuel Cerps ,&nbsp;Sangeetha Ramu ,&nbsp;Olof Gidlöf ,&nbsp;Mandy Menzel ,&nbsp;Karl Swärd ,&nbsp;Lena Uller ,&nbsp;Bengt-Olof Nilsson","doi":"10.1016/j.bbrep.2025.102105","DOIUrl":"10.1016/j.bbrep.2025.102105","url":null,"abstract":"<div><div>The human cathelicidin LL-37 is active against both bacteria and viruses, but it also shows immunomodulatory properties. Here, we assess the impact of LL-37 on viral signaling in human airway epithelial BEAS-2B cells infected with the respiratory pathogen rhinovirus (RV). We show that LL-37 (4 μM) enhances RV-induced expression of interferon β (IFNβ) transcript and reduces viral-load. LL-37-evoked potentiation of RV-stimulated IFNβ does not involve up-regulation of the classical viral TLR3, MDA5 and RIG-I receptors. Moreover, the LL-37-induced stimulation of IFNβ expression in the presence of RV is abolished by chloroquine, an inhibitor of endosomal acidification. Interestingly, RV + LL-37-induced stimulation of IFNβ is observed in the absence but not in the presence of the Ca²⁺ chelating agent EGTA, indicating that Ca²⁺ is critical for this effect. Indeed, we demonstrate that LL-37 increases intracellular [Ca²⁺] in cells loaded with the fluorescent Ca²⁺ indicator Fluo-4 AM. Furthermore, we reveal that treatment with RV in combination with the Ca²⁺ ionophore A23187 promotes IFNβ expression, showing the importance of Ca²⁺. In conclusion, we demonstrate that LL-37 acts in synergy with RV to enhance IFNβ expression and that this effect involves LL-37-induced increase in intracellular [Ca²⁺].</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102105"},"PeriodicalIF":2.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330382","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":"Targeting tryparedoxin-dependent peroxidase (TXNPx) enzyme to identify repurposing drug candidates from FDA-approved drugs and natural products using virtual screening, ADME/Tox and MD simulations","authors":"Eman Shorog ,&nbsp;Sabina Yasmin ,&nbsp;Rani Mansuri ,&nbsp;Arpit Raj ,&nbsp;Mohammad Ovais Dar ,&nbsp;Sumel Ashique ,&nbsp;Qazi Mohammad Sajid Jamal ,&nbsp;Ali H. Alharbi ,&nbsp;Mushtaq Ahmad Wani ,&nbsp;Mohammad Yousuf Ansari","doi":"10.1016/j.bbrep.2025.102096","DOIUrl":"10.1016/j.bbrep.2025.102096","url":null,"abstract":"<div><div>Protozoan are parasitic organisms that can cause significant diseases worldwide, such as Chagas disease, African sleeping sickness, and Leishmaniasis. In this study, we performed docking studies on type II tryparedoxin-dependent peroxidase (PDB ID: 2VUP) using a Zinc database having natural products library and FDA-approved drugs. The top compounds identified are F1762–0560, F1855-0030, FDA_339, FDA_461, tetrahydrobenzo-tetraphenoxirene, and ketoconazole. These compounds were further performed the molecular dynamics simulations studies. The docking results has suggested that top Docking Scores compounds are F17620560 (−8.6 kcal/mol), F1855-0030(−7.8 kcal/mol), FDA_339 (−7.0 kcal/mol), FDA_461 (−7.0 kcal/mol), tetrahydrobenzo-tetraphenoxirene (−7.5 kcal/mol) and, ketoconazole (−6.7 kcal/mol). The common binding affinity amino acids are SER 37, LYS 38, CYS 39, LYS 43, GLU 81 and PHE 85. The top scoring compounds (F1762-0560) has showed interactions with the target protein through hydrogen bonding and stacking interactions, particularly with SER 37, CYS 39, and LYS 43. We further investigated the stability of six ligand-TXNPx complexes over 200 ns. The results indicated good structural stability (RMSD: 0.05–0.20 nm; Rg: 1.45–1.52 nm), with F0556–0242 and F1762-0560 showing the least fluctuations. FDA_461 has the most hydrogen bonds (up to 5), while Ketoconazole was more flexible (RMSD peak: 0.25 nm). These findings suggest that F0556–0242, F1762-0560, and FDA_461 are promising candidates.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102096"},"PeriodicalIF":2.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330380","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":"AEBP1-GLI1 pathway attenuates the FACT complex dependency of bladder cancer cell survival","authors":"Haruka Kurosu ,&nbsp;Norika Yamada ,&nbsp;Ritsuko Nakamura ,&nbsp;Hideaki Ito ,&nbsp;Koji Ohnishi ,&nbsp;Akihito Inoko ,&nbsp;Miho Riku ,&nbsp;Tomoaki Muramatsu ,&nbsp;Naoto Sassa ,&nbsp;Kenji Kasai","doi":"10.1016/j.bbrep.2025.102101","DOIUrl":"10.1016/j.bbrep.2025.102101","url":null,"abstract":"<div><div>The facilitates chromatin transcription (FACT) complex is composed of SSRP1 and SUPT16H subunits and participates in nucleosomal reorganization; hence, FACT inhibitors are considered promising therapeutics for malignant tumors. Here, we show that adipocyte enhancer binding protein 1 (AEBP1) attenuates the dependency of bladder cancer cell survival on the FACT complex <em>via</em> the expression of GLI1, a pivotal transcription factor in Hedgehog signaling. In <em>AEBP1</em>-high expressing bladder cancer cell lines, <em>AEBP1</em> knockdown inhibited cellular proliferation and induced the marker expression of apoptosis and DNA damage/replication stress. RNA-sequencing revealed that <em>AEBP1</em> knockdown suppressed the expression of <em>SSRP1</em> and <em>SUPT16H</em>; however, the knockdown of both subunits was less effective than <em>AEBP1</em> knockdown in inducing apoptosis or DNA damage markers in <em>AEBP1</em>-high expressing cells. <em>AEBP1</em> knockdown reduced the protein levels of GLI1, and treatment with the GLI-specific inhibitor GANT61 induced markers that were not suppressed by the forced expression of AEBP1. These findings suggest that AEBP1-mediated GLI1 expression reduces the FACT complex dependency of bladder cancer cell survival.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102101"},"PeriodicalIF":2.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330381","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":"New breast cancer marker BF-09 is overexpressed in tumor extracts and secreted in serum","authors":"Christine Chavany ,&nbsp;Jeffrey Dea ,&nbsp;Rafael Hernández González ,&nbsp;Rosaura P.C. Valle ,&nbsp;Moncef Jendoubi","doi":"10.1016/j.bbrep.2025.102097","DOIUrl":"10.1016/j.bbrep.2025.102097","url":null,"abstract":"<div><h3>Background</h3><div>CA 15-3 and CA 27–29 are widely used serum biomarkers for breast cancer with limited utility due to low sensitivity in early-stage disease. This study details the discovery of BF-09, a new breast cancer marker with potential for wider application.</div></div><div><h3>Method</h3><div>Antibodies were screened against tumor biopsy extracts (n = 115) relative to non-cancer (n = 190) specimens using an immunoscreening array. Western blot was done to determine the molecular weight of the antibody target and test secretion in cell culture medium. A sandwich ELISA was developed and tested on mouse xenograft serum to confirm in vivo secretion. A preliminary set of cancer (n = 14) and non-cancer (n = 13) human serum samples was similarly tested to confirm the biomarker could be measured in human blood. HuProt Human Protein Array was used for target protein identification.</div></div><div><h3>Results</h3><div>BF-09 antibody was selected for further study because its protein target was elevated in both early and late-stage cancer extracts (p &lt; 0.05). On Western blot, BF-09 antibody reacted against a protein band of around 15 kDa. ELISA results confirmed that the biomarker was secreted in both mouse and human serum in quantifiable amounts. BF-09 protein had higher median concentration in serum of cancer patients (p &lt; 0.0001) compared to non-cancer patients. Phage display and HuProt array revealed the protein target as SAGA-associated factor 29.</div></div><div><h3>Conclusion</h3><div>Due to its elevated presence in early-stage tumor tissue and its measurable secretion into serum, BF-09 is a promising breast cancer marker for further study.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102097"},"PeriodicalIF":2.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330467","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":"Brief ambulatory reloading elevates muscle protein synthesis but does not prevent disuse atrophy in hindlimb-unloaded rats","authors":"Michael P. Wiggs ,&nbsp;Carla MC. Nascimento ,&nbsp;Kevin L. Shimkus ,&nbsp;James D. Fluckey","doi":"10.1016/j.bbrep.2025.102100","DOIUrl":"10.1016/j.bbrep.2025.102100","url":null,"abstract":"<div><div>Disuse muscle atrophy remains a major challenge in contexts such as prolonged bed rest or microgravity. Here, we investigated whether brief bouts of ambulatory reloading could attenuate skeletal muscle atrophy caused by five days of hindlimb unloading (HU) in rats. Using a deuterium oxide tracer, we measured integrative protein synthesis (fractional synthesis rate, FSR) in the soleus, plantaris, and gastrocnemius muscles, including distinct portions of the muscle that are composed mostly of red, white, and mixed fibers. HU significantly reduced both muscle mass and FSR in the predominantly slow-twitch soleus and in the predominantly fast gastrocnemius. Intermittent ambulatory reloading (HU + AR) partially restored FSR in the soleus and gastrocnemius but did not recover soleus or gastrocnemius mass to control levels. The plantaris muscle showed no differences in mass or FSR among groups, suggesting muscle-specific responses to unloading and reloading. Fiber-type analyses revealed that portions of the gastrocnemius that are mostly red fibers had higher baseline FSR than mixed or white portions, while HU consistently depressed protein synthesis across all fiber types. In conclusion, although intermittent ambulation increased protein synthesis during HU, it was not sufficient to prevent overall muscle mass loss. These findings emphasize the importance of both the duration and intensity of loading in preserving skeletal muscle during periods of disuse.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102100"},"PeriodicalIF":2.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306394","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":"BDNF gene therapy rescues neuronal function via unique and common transcriptional responses in Aβ and tau-driven Alzheimer's disease mouse models","authors":"Siqi Tang ,&nbsp;Wenshu Luo ,&nbsp;Cheng Cheng ,&nbsp;Leshan Shen ,&nbsp;Xia Wu ,&nbsp;Xiao Xiao","doi":"10.1016/j.bbrep.2025.102089","DOIUrl":"10.1016/j.bbrep.2025.102089","url":null,"abstract":"<div><div>Brain-derived neurotrophic factor (BDNF) protects neurons from degeneration, making it a promising therapeutic target for Alzheimer's disease (AD). However, the genetic regulation resulting from BDNF overexpression in the brain remains to be further illustrated. Using APP/PS1 and rTg4510 mouse models, we analyzed hippocampal transcriptomes after intrahippocampal AAVT42-<em>BDNF</em> injection. In APP/PS1 mice with Aβ accumulation, BDNF upregulated genes involved in neuronal signaling and downregulated neurodegenerative pathways. In rTg4510 mice with p-tau pathology, upregulated genes were associated with cell differentiation and neuronal development, while downregulated genes were related to metabolism and biosynthesis. A comparison of differentially expressed genes (DEGs) between the two strains identified eight commonly upregulated genes (<em>Cecr2, Cdhr1, Dusp6, Pam, Rasd1, Dusp4, Htr5b, Tmem117</em>) and two downregulated genes (<em>Abhd14a</em>, <em>Pmel</em>). Notably, three genes - <em>Npy, Crh</em>, <em>Tac1</em>-were upregulated in both models, suggesting shared neuroprotective mechanisms. These findings reveal distinct and common genetic responses to BDNF in Aβ and p-tau pathogenesis, supporting its potential as a therapeutic strategy for AD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102089"},"PeriodicalIF":2.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306393","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":"Expression and purification of a broad-spectrum human protease inhibitor in Pichia pastoris","authors":"Varsha Bhakta ,&nbsp;Negin Chaeichi Tehrani ,&nbsp;Antje Ask ,&nbsp;William P. Sheffield","doi":"10.1016/j.bbrep.2025.102092","DOIUrl":"10.1016/j.bbrep.2025.102092","url":null,"abstract":"<div><div>Alpha-1 antitrypsin (AAT) is the most abundant member of the serpin superfamily of protease inhibitors found in human plasma. Expression of a broad-spectrum AAT variant (AAT M358R) and an AAT variant (AAT-RC-2) that specifically inhibits coagulation Factor XIa (FXIa) in the methylotrophic yeast <em>Pichia pastoris</em> were compared. When protein secretion was directed by the 85 amino acid <em>Saccharomyces cerevisiae</em> alpha mating factor (AMF) prepro signal sequence 1 (ss1), AAT-RC-2 was purified as a 45 kDa homogeneous polypeptide preparation, but AAT M358R was heterogeneous. Replacement of the ss1 prepro sequence with any of 5 presequences lacking pro sequences eliminated the heterogeneity. The highest yield was obtained with ss3-AAT M358R, where ss3 was the 19 amino acid <em>Saccharomyces cerevisiae</em> AMF presequence. Enzymatic deglycosylation of ss1-AAT M358R converted its high molecular weight heterogeneity into a simple combination of 55 kDa and 45 kDa polypeptides consistent with failure to remove the AMF presequence and inhibition of the Kex2 propeptide convertase by AAT M358R. Purified ss3-AAT M358R inhibited FXIa significantly more rapidly than <em>E. coli</em>-derived AAT M358R with indistinguishable reaction stoichiometry; purified ss1-AAT-RC-2 did not differ from its <em>E. coli</em>-derived counterpart in either kinetic parameter. Both AAT variants formed denaturation-resistant complexes with FXIa. Substitution of the AMF prepro sequence with its constituent presequence eliminated the protein expression problem caused by inhibition of the <em>Pichia pastoris</em> propeptide processing machinery by AAT M358R and will make feasible comparison of AAT M358R and AAT-RC-2 in animal models of thrombosis and bleeding.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102092"},"PeriodicalIF":2.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291353","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":"LncRNAs IFNG-AS1 and TH2LCRR as potential biomarkers of Th1/Th2 imbalance in diabetic nephropathy: From bioinformatics to experimental validation","authors":"Seyed Amir Hossein Hosseini ,&nbsp;Parisa Ajorlou ,&nbsp;Maryam Salehian ,&nbsp;Aghdas Dehghani","doi":"10.1016/j.bbrep.2025.102093","DOIUrl":"10.1016/j.bbrep.2025.102093","url":null,"abstract":"<div><h3>Background</h3><div>The inflammatory response is a pivotal mechanism underlying the progression of type 2 diabetes mellitus (T2DM) into diabetic nephropathy (DN). Upstream lncRNAs regulate inflammatory molecules, and their dysregulation can disrupt immune homeostasis. Th1/Th2 imbalance is one of the most significant causes of DN progression. This research aims to uncover novel biomarkers and elucidate the underlying molecular mechanisms involved in DN.</div></div><div><h3>Methods</h3><div>The GSE135390 dataset was analyzed to identify differentially expressed genes (DEGs) associated with Th1 cell differentiation. Based on literature review and NcPath databases, IFNG-AS1(Th1) and TH2LCRR (Th2) were selected as the top lncRNAs. To validate our bioinformatics findings, real-time PCR was conducted on 90 participants categorized into four groups: 30 with T2DM, 30 with DN (15 with microalbuminuria and 15 with ESRD), and 30 healthy controls.</div></div><div><h3>Results</h3><div>The analysis of real-time PCR results revealed a notable upregulation in IFNG-AS1 expression in ESRD patients compared to individuals with T2DM and healthy controls. Moreover, a significant increase in IFNG-AS1 expression was observed in patients with microalbuminuria relative to healthy subjects. Conversely, TH2LCRR expression was notably reduced in patients with ESRD, microalbuminuria, and T2DM compared to healthy individuals. Expression of IFNG-AS1 and TH2LCRR showed strong correlation with biochemical markers, including HbA1c, ESR, BUN, GFR, and albumin.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potential role of IFNG-AS1 and TH2LCRR as key regulators in the immunopathogenesis of DN. Their dysregulated expression may contribute to Th1/Th2 imbalance, providing a deeper understanding of immune-mediated mechanisms involved in DN progression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102093"},"PeriodicalIF":2.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288922","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}