Journal of physiological investigation最新文献

{"title":"Candida tropicalis Alters Barrier Permeability and Claudin-1 Organization in Intestinal Epithelial Cells.","authors":"Ha The Doan, Yi-Ling Chiu, Li-Chieh Cheng, Rae Apaivongse Coad, Hao-Sen Chiang","doi":"10.4103/ejpi.EJPI-D-24-00090","DOIUrl":"10.4103/ejpi.EJPI-D-24-00090","url":null,"abstract":"<p><strong>Abstract: </strong>Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic inflammation of the gut and compromised intestinal barrier function, resulting from aberrant immune responses targeting the intestinal microbiota. While the involvement of Candida albicans in IBD pathogenesis is well-documented, the role of non- albicans Candida species in IBD remains less understood. Recent studies have identified a correlation between elevated levels of Candida tropicalis , a notable non- albicans opportunistic fungus, and the development of IBD. However, the precise impact of C. tropicalis on intestinal barrier function is not well elucidated. To address this knowledge gap, we utilized a cell model comprising polarized Caco-2 monolayers, which mimic the intestinal epithelium, to investigate the interaction between C. tropicalis and intestinal barrier function. Our results showed that incubation with C. tropicalis influenced transepithelial electrical resistance and increased permeability to the small molecule lucifer yellow, but did not affect permeability to the larger molecule fluorescein isothiocyanate-dextran. In addition, we observed internalization of the tight junction protein claudin-1 in the Caco-2 monolayers. Further experiments using Caco-2 monolayers exposed to the dectin-1 ligand zymosan induced similar changes in the distribution of claudin-1 but did not alter monolayer permeability. These findings suggest that C. tropicalis specifically affects intestinal barrier integrity and permeability to smaller solutes in intestinal epithelial cells.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"67-76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367223","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":"Age- and Urothelium-related Changes in Hydrogen Sulfide-induced Responses in Mouse Bladder.","authors":"Fatma Aydinoglu, Tugba Toyran, Nuran Ogulener","doi":"10.4103/ejpi.EJPI-D-24-00078","DOIUrl":"10.4103/ejpi.EJPI-D-24-00078","url":null,"abstract":"<p><strong>Abstract: </strong>The alterations in bladder function are associated with aging. Hydrogen sulfide (H 2 S) is a gaseous neurotransmitter that is synthesized in the urinary bladder and is suggested to regulate bladder smooth muscle tone. The effects of age and urothelium on the L-cysteine/H 2 S-induced relaxant responses were investigated in young (3-4 months) and aged (23-24 months) mice. The relaxant responses to endogenous H 2 S (L-cysteine) augmented in denuded urothelium bladder tissue in both age groups. However, the relaxant responses to exogenous H 2 S (sodium hydrogen sulfide: 1 μM - 3 mM) did not change by disruption of the urothelium. The contractile response to carbachol increased in intact bladder tissues of aged mice compared to young mice. On the other hand, contractile responses to carbachol decreased in the denuded bladder tissues of aged compared to young mice. In addition, cystathionine-β-synthase, cystathionine-γ-lyase (CSE), and 3 mercaptopyruvate sulfurtransferase (3-MST) enzymes which are responsible for H 2 S synthesis were intensively detected in the urothelium and vascular smooth muscle of bladder by immunohistochemistry. CSE and 3-MST were observed lesser in the smooth muscle of aged bladder tissue. These results suggest that relaxation to the L-cysteine/H 2 S pathway and contraction to carbachol of the bladder are affected by aging and urothelium. H 2 S- and urothelium-related molecular and biological changes may be responsible for bladder dysfunctions by aging. Understanding the mechanisms involved in chemical and mechanical signaling of the H 2 S pathway may provide important insights into the development of novel targets for the clinical management of age-related bladder dysfunctions in human such as overactive bladder, lower urinary tract symptoms, and other urological diseases. In this context, it is important to note that L-cysteine/H 2 S pathway may be recognized a new therapeutic target bladder disorders.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"22-30"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831456","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":"Indoleamine 2,3-Dioxygenase 1/Aryl Hydrocarbon Receptor Feedback Loop Mediates Anti-inflammation in lipopolysaccharide-stimulated Astrocytes to Dampen Inflammatory Neurotoxicity.","authors":"Yu-Ling Gan, Yi-Hsuan Lee","doi":"10.4103/ejpi.EJPI-D-24-00089","DOIUrl":"10.4103/ejpi.EJPI-D-24-00089","url":null,"abstract":"<p><strong>Abstract: </strong>Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates cell immune responses in a cell type-specific and ligand-dependent manner. In the central nervous system, astrocytic AhR plays important roles in regulating neuroinflammation by mediating responses to endogenous ligands generated from the inflammation-induced indoleamine 2,3-dioxygenase 1 (IDO1)/kynurenine (KYN) pathway. We previously demonstrated that reduction of AhR expression decreases lipopolysaccharide (LPS)-induced pro-inflammatory responses in microglia. However, the role of AhR in the astrocytic immune responses and its subsequent effects on microglial activation and neurotoxicity remain unclear. In this study, we used LPS-induced neuroinflammation in rat cortical glia-neuron (GN) mix cultures, which increased the expression of tumor necrosis factor-α and interleukin-6 and microglial activation. These proinflammatory responses were attenuated by a specific AhR agonist 6-formylindolo [3,2-b] carbazole (FICZ), but not by the AhR antagonist CH223191. CH223191, which inhibits LPS- and FICZ-induced AhR activation, enhanced neurotoxicity induced by LPS-glutamate co-treatment in GN mix cultures. Furthermore, inhibition of AhR expression and activation enhanced LPS-induced proinflammatory responses, and LPS-induced AhR activation was abrogated by the inhibition of IDO1 expression in astrocytes. Notably, AhR knockdown inhibited the anti-inflammatory effects of KYN while enhancing LPS-induced IDO1 expression in astrocytes, suggesting that AhR mediates the anti-inflammatory effect of KYN and the negative feedback regulation of IDO1 expression. Finally, we examined the role of astrocytic AhR in inflammatory astrogliosis-induced neurotoxicity by treating primary cortical neurons with LPS-treated astrocyte-conditioned medium (ACM). The results revealed that ACM derived from siAhR-transfected astrocytes increased neurotoxicity. In conclusion, inflammation-activated AhR mediates the anti-inflammatory effects and negative feedback regulation of the IDO1/KYN pathway in astrocytes, thereby dampening inflammatory astrogliosis-induced neurotoxicity.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026293","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":"Neng-Jing-Huo Essential Oil Blend Inhibits Lipopolysaccharide-Induced Intracellular Reactive Oxygen Species Accumulation, Inflammation, and Apoptosis in Renal Tubular Epithelial Cells.","authors":"Chin-Ya Su, Kai-Fu Chang, Chih-Yen Hsiao, Nu-Man Tsai","doi":"10.4103/ejpi.EJPI-D-24-00096","DOIUrl":"10.4103/ejpi.EJPI-D-24-00096","url":null,"abstract":"<p><strong>Abstract: </strong>Acute kidney injury (AKI) is a common serious complication of sepsis that is characterized by the rapid deterioration of kidney function. Neng-Jing-Huo (NJH) is an essential oil blend, including Gaultheria procumbens, Zingiber officinale, Bulnesia sarmientoi, Artemisia vulgaris , and Styrax benzoin oils, with antimicrobial, antioxidant, and anti-inflammatory activities. Here, we investigated the effects of NJH on oxidative stress, inflammatory response, and apoptosis in an in vitro septic AKI model and explored the underlying mechanisms. A cellular model of septic AKI was established using lipopolysaccharide (LPS). Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Action mechanisms of NJH were analyzed using the Griess reagent, 2',7'-dichlorodihydrofluorescein diacetate, 5,5',6,6' tetrachloro-1,1'3,3' tetraethylbenzimidazolcarbocyanine iodide, annexin V, caspase activity, western blotting, and semi-quantitative reverse transcription polymerase chain reaction assays. Results showed that pretreatment with NJH significantly improved cell survival and suppressed nitric oxide (NO) production in LPS-stimulated NRK-52E renal tubular epithelial cells. NJH also decreased the levels of intracellular reactive oxygen species and maintained the mitochondrial membrane potential by upregulating the nuclear factor (NF) erythroid 2-related factor 2/heme oxygenase-1 levels and downregulating the NADPH oxidase 4 levels. In addition, NJH suppressed the activation of the toll-like receptor 4/NF-κB and NLRP3/caspase-1 pathways, thereby decreasing the inflammatory response in LPS-stimulated NRK-52E cells. Moreover, NJH decreased the levels of Bax, caspase-9, and caspase-3 but increased those of Bcl-2, which led to a reduction in LPS-induced apoptosis. Overall, our findings revealed that NJH ameliorated LPS-induced damage in NRK-52E cells by inhibiting oxidative stress, inflammation, and apoptosis, highlighting its therapeutic potential for septic AKI.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"57-66"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026294","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":"CircRNA-0013747 Promotes Mesangial Cell Proliferation in Immunoglobulin A Nephropathy through Modulation of the Warburg Effect.","authors":"Huimei Zou, Wenli Deng, Lifen Xu, Mingjun Shi, Lingling Liu, Lei Gong, Daolin Cui, Fan Zhang","doi":"10.4103/ejpi.EJPI-D-24-00095","DOIUrl":"10.4103/ejpi.EJPI-D-24-00095","url":null,"abstract":"<p><strong>Abstract: </strong>Immunoglobulin A nephropathy (IgAN) is characterized by aberrant mesangial cell (MC) proliferation, which is a critical determinant of glomerular sclerosis and renal dysfunction. Previous studies have highlighted the role of pyruvate kinase M2 (PKM2)- mediated aerobic glycolysis in promoting MC growth and the progression of kidney diseases. However, the precise mechanisms underlying PKM2 dysregulation in IgAN remain unclear. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as pivotal regulators in various diseases, yet their role in IgAN has not been fully elucidated. In this study, we investigated the expression and functional significance of circRNA_0013747 in IgAN, focusing on its interaction with microRNA-330-3p (miR-330-3p) and its downstream effects on PKM2-mediated aerobic glycolysis. Our results demonstrated a significant upregulation of circRNA_0013747 in kidney biopsy samples from IgAN patients. Functional analyses revealed that circRNA_0013747 promoted MC proliferation and activated PKM2-mediated aerobic glycolysis. Importantly, these effects were attenuated by the upregulation of miR-330-3p, which was found to physically interact with circRNA_0013747, thereby inhibiting its function. Mechanistically, circRNA_0013747 acted as a sponge for miR-330-3p, relieving its suppressive effects on PKM2 expression. These findings suggest that circRNA_0013747 enhances glycolysis and proliferation in MCs through modulation of the miR-330-3p/PKM2 signaling axis. These results offer novel insights into the pathogenesis of IgAN and could contribute to new therapeutic approaches for this disease. Specifically, targeting circRNA_0013747 or modulating its interaction with miR-330-3p may provide a means to inhibit MC proliferation and aerobic glycolysis, thereby slowing the progression of IgAN and preserving renal function. Such therapeutic strategies hold the promise of substantial benefits for patients with IgAN and could pave the path toward developing more potent treatments for a wider range of renal diseases.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"43-56"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191679","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":"Apelin-13 Ameliorates Sepsis-induced Brain Injury by Activating Phosphatase and Tensin Homolog-induced Putative Kinase 1/Parkin-mediated Mitophagy and Modulating Nucleotide-binding Oligomerization Domain-like Receptor Pyrin Domain-Containing 3-driven Pyroptosis in Rats.","authors":"Fan Jiang, Junxia Dong, Yi Han","doi":"10.4103/ejpi.EJPI-D-24-00086","DOIUrl":"10.4103/ejpi.EJPI-D-24-00086","url":null,"abstract":"<p><strong>Abstract: </strong>Sepsis is a life-threatening condition that often results in severe brain injury, primarily due to excessive inflammation and mitochondrial dysfunction. This study aims to investigate the neuroprotective effects of Apelin-13, a bioactive peptide, in a rat model of sepsis-induced brain injury (SBI). Specifically, we examined the role of Apelin-13 in regulating mitophagy through the phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin pathway and its impact on nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis and oxidative stress. A sepsis model was induced in male Sprague-Dawley rats ( n = 110, 200-230 g, 12 weeks old) through cecal ligation and puncture (CLP). The septic rats received Apelin-13 (20 μg/kg, intravenously), either alone or combined with mitochondrial division inhibitor-1 (Mdv-1), a mitophagy inhibitor, before undergoing CLP surgery. Survival rates were assessed over a 72-h period, while the cognitive function was evaluated using the Morris water maze over 5 days. Western blotting and immunohistochemistry were utilized to measure the expression levels of NLRP3, cleaved caspase-1, N-terminal fragment of gasdermin D, PINK1, and Parkin in the brains of the rats. In addition, enzyme-linked immunosorbent assays were conducted to evaluate markers of oxidative stress and inflammatory responses in brain samples. Apelin-13 significantly improved survival rates and cognitive function and mitigated brain injury in septic rats. The treatment enhanced PINK1/Parkin-mediated mitophagy and suppressed NLRP3 inflammasome activation, leading to a reduction in pyroptosis, inflammation, and oxidative stress. Inhibition of mitophagy by Mdv-1 significantly reversed the protective effects of Apelin-13 in septic rats. Our findings suggest that Apelin-13 provides neuroprotection in sepsis by modulating mitophagy and inhibiting pyroptosis. These results highlight the potential of Apelin-13 as a therapeutic strategy for SBI.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"31-42"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961110","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":"Exploring the Effects of Tomatidine ((3β, 5α, 22β, and 25β)-Spirosolan-3-ol) on Voltage-gated Na+ currents: Insights Into Its Ionic Mechanisms of Action on Current Magnitude, Gating, and Frequency Dependence.","authors":"Tso-Lin Lin, Edmund Cheung So, Sheng-Nan Wu","doi":"10.4103/ejpi.EJPI-D-24-00076","DOIUrl":"https://doi.org/10.4103/ejpi.EJPI-D-24-00076","url":null,"abstract":"<p><strong>Abstract: </strong>Tomatidine, a major tomato glycoalkaloid, is effective for the prevention of skeletal muscle wasting and enhancing mitophagy. However, its effects on transmembrane ionic currents are not well explored. In this study, we explored the interactions between tomatidine and Na+ current. GH3 or Neuro-2a cells were used for recording the ion currents employing modified patch-clamp technique under whole-cell configuration. Tomatidine increased both the peak, (transient Na+ current [INa (T)]) and sustained (late Na+ current [INa (L)]) components of voltage-gated Na+ current (INa) in a concentration-dependent manner, with the concentration required for 50% stimulation values of 43.3 μM and 3.1 μM, respectively. The steady-state current-voltage relationship of INa (T) remained unchanged; however, the steady-state inactivation curve of INa (T) in the presence of 3 μM tomatidine was shifted to less depolarized potential by around 6 mV. Tomatidine enhanced the window INa (window Na+ current [INa (W)]), which were attenuated by the ranolazine (Ran) and carbamazepine (CBZ). During a train of depolarizing pulses, tomatidine slowed the exponential decay of INa (T), and this effect was reversed by Ran or dapagliflozin. Tomatidine increased both fast and slow recovery time constants from INa (T) block, affecting the recovery time course. Tomatidine increased the amplitude of persistent Na+ current in response to a sinusoidal waveform. In neuro-2a cells, tomatidine increased INa (T) amplitude and slowed its inactivation, with this effect being attenuated by Ran or CBZ. In conclusion, tomatidine enhanced magnitude and modified its gating behaviors.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":"67 6","pages":"298-311"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788180","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":"A Multi-ingredient Supplement Reduced Markers of Muscle Damage after a Rugby Match in Collegiate Male Players.","authors":"Chang-Li Hsueh, Wang-Shiang Huang, Chen-Kang Chang","doi":"10.4103/ejpi.EJPI-D-24-00074","DOIUrl":"10.4103/ejpi.EJPI-D-24-00074","url":null,"abstract":"<p><strong>Abstract: </strong>Eccentric exercise and collisions that lead to muscle damage are common place among athletes. This study aimed to investigate the effect of a multi-ingredient supplement (MIS), containing the extracts of turmeric, chicken meat, and apple and ancient peat, on markers of muscle damage in collegiate male players following a rugby match. A position-matched, double-blind, randomized, and crossover design was employed in this study. Each trial consisted of a 14-day supplementation period, followed by a 15-a-side rugby match. A total of 13 participants, eight forward and five backs, with a mean height of 1.76 ± 0.08 m and a mean weight of 86.0 ± 22.8 kg, were included. Blood samples were collected before, immediately, 24 h, and 48 h after the match. Both the MIS ( P < 0.001, d = 1.86) and placebo trials ( P = 0.002, d = 1.97) exhibited a significant increase in plasma creatine kinase and lactate dehydrogenase (LDH) concentrations from the baseline immediately after the match. However, plasma creatine kinase concentration in the MIS trial was significantly lower at 24 h postmatch compared to the placebo trial ( P = 0.029, d = 0.90). Moreover, plasma LDH concentration returned to the baseline level 24 h after the match in the MIS trial, while it remained elevated in the placebo trial ( P = 0.001, d = 1.07). In either trials, the plasma tumor necrosis factor-α and malondialdehyde concentrations were not significantly different. In conclusion, the MIS can alleviate muscle damage markers after a rugby match without changes in inflammation and oxidative stress markers.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"293-297"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735502","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":"Elevations of N-Terminal Mid-Fragment of Osteocalcin and Cystatin C Levels are Associated with Disorders of Glycolipid Metabolism and Abnormal Bone Metabolism in Patients with Type 2 Diabetes Mellitus Complicated with Osteoporosis.","authors":"Xiaofang Guo, Yun Shen, Teng Du, Yan He, Jie Lu, Qianhong Yang","doi":"10.4103/ejpi.EJPI-D-24-00042","DOIUrl":"10.4103/ejpi.EJPI-D-24-00042","url":null,"abstract":"<p><strong>Abstract: </strong>Type 2 diabetes mellitus (T2DM) patients always develop osteoporosis (OP). We examined correlations of N-terminal mid-fragment of osteocalcin (N-MID) and cystatin C (Cys C) levels with glycolipid metabolism, bone metabolism markers, and bone mineral density (BMD) in elderly T2DM-OP patients. Grouping was performed as per whether T2DM patients developed OP (OP group) or not (N-OP group). N-MID and Cys C were measured using enzyme-linked immunosorbent assay, with correlations with glycolipid metabolism, bone metabolism indicators, and BMD analyzed using Pearson's correlation coefficient. Elderly T2DM-OP patients showed elevated disease duration, age, body mass index, glycated hemoglobin (HbA1c), Homer's insulin resistance (HOMA-IR), total cholesterol (TC), beta-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX), tartrate-resistant acid phosphatase 5b (TRACP-5b), N-MID and Cys C levels, and reduced high-density lipoprotein cholesterol (HDL-C), bone alkaline phosphatase (B-ALP), aminoterminal propeptide of type I procollagen (PINP), carboxyterminal propeptide of type I procollagen (PICP), BMD, and calcium supplementation. N-MID and Cys C were positively correlated with HbA1c, HOMA-IR, TC, β-CTX, and TRACP-5b and negatively with HDL-C, B-ALP, PINP, PICP, and BMD in elderly T2DM-OP patients. Conclusively, the abnormal elevations of serum N-MID and Cys C were associated with glycolipid metabolism disorder, abnormal bone metabolism, and decreased BMD in elderly T2DM-OP patients.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"335-343"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305793","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":"Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells.","authors":"Yi-Yang Chen, Ying-Hsuan Wang, Chih-Cheng Chen, Cih-En Huang, Chia-Chen Hsu, Shu-Huei Hsiao, Yu-Wei Leu","doi":"10.4103/ejpi.EJPI-D-24-00047","DOIUrl":"10.4103/ejpi.EJPI-D-24-00047","url":null,"abstract":"<p><strong>Abstract: </strong>Myeloproliferative neoplasms (MPNs) are blood cancers caused by mutations that originate from hematopoietic stem cells. More than 50%-90% of MPN patients had a dominant negative valine (V) to phenylalanine (F) mutation at the Janus kinase 617 codon (JAK2V617F) within the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway; however, this mutation was also found in a high percentage of the general population, its penetrance varied, and its onset was shown to be polygenic. Consequently, it is still unknown what molecular mechanism underlies the MPN transformation produced by JAK2V617F. Patients with MPN have been shown to have dysregulation of noncoding RNAs, such as microRNA (miRNA) and PIWI-interacting RNA (piRNA), although there is not any concrete proof that JAK2V617F alone is responsible for the aberrant regulation of miRNA and piRNA. Human wild type versus V617F-mutated JAK2 are expressed in mouse Ba/F3 cells, and the expressed small and total RNAs were subjected to next generation sequencing analysis to determine the direct induction. Differentially expressed miRNAs, gene expression, and transcript and gene variations were found between exogenously expressed JAK2 and JAK2V617F in Ba/F3 cells. The differently expressed variations contained enriched transposable elements and piRNAs, indicating a rearranged epigenome. The results of the pathway analysis show that the transformation that self-validated the chosen sequencing target genes is impacted by the JAK-STAT pathway. The induction route is functionally conserved, according to exogenously produced miRNA and gene expression. These results may clarify how the JAK2V617F induces transformation.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"344-354"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336055","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}