International journal of physiology, pathophysiology and pharmacology最新文献

{"title":"Exploring psychophysiological stress variability across menstrual phases: insights from a tertiary care centre in eastern Uttar Pradesh.","authors":"Prashant Mishra, Charushila Rukadikar, Manoj Prithviraj, Geetha Mohan, Atul Rukadikar, Sundhar Mohandas, Samiksha Nishad","doi":"10.62347/KZXQ7629","DOIUrl":"10.62347/KZXQ7629","url":null,"abstract":"<p><strong>Objectives: </strong>The menstrual cycle is the primary biological rhythm orchestrated by the hypothalamic-pituitary-ovarian axis, subject to complex hormonal fluctuations. These hormonal changes modulate cardiovascular activity, changes in heart rate variability, blood pressure, and psychological states. They often appear as premenstrual syndrome in the luteal phase. Previous studies suggested that stress reactivity is different across menstrual stages but inconsistently. For the present study, we aimed to explore psychophysiological stress reactivity following the follicular and luteal phases of the menstrual cycle in women aged 18 to 30 years.</p><p><strong>Methods: </strong>Several menstrual phases were assessed by luteinizing hormone test. All participants underwent laboratory studies in the follicular and luteal stages as follows: basal blood pressure and heart rate measurements were taken, whereas psychological stress was measured with the State-Trait Anxiety Inventory (STAI). Stress responses were elicited using the cold pressor test, and data were quantified using paired t-test and correlation analyses.</p><p><strong>Results: </strong>Upon analysing the results, it was found that basal blood pressure and heart rate were not significantly different between the three phases. However, diastolic blood pressure rose considerably during the luteal phase following the cold pressor test. Trait anxiety scores were significantly increased during the luteal phase, and significant differences in state anxiety were detected only after the stressor in this phase.</p><p><strong>Conclusions: </strong>These findings indicated that the luteal phase could reflect maladaptive psychophysiological stress reactivity. Taken in aggregate, the findings highlight the relevance of menstrual cycle phases in stress assessments and treatment interventions, promoting individualized methods in women's healthcare.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"18 1","pages":"17-28"},"PeriodicalIF":0.0,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid-sensing ion channels and their role in controlling pain in the post-operative stage.","authors":"Gowri Warikoo, Amber Sun, Xiang-Ping Chu","doi":"10.62347/OUZV9045","DOIUrl":"10.62347/OUZV9045","url":null,"abstract":"<p><p>Acid-sensing ion channels (ASICs) are proton-gated cation channels that are widely expressed throughout the nervous system and play a central role in sensory processing, particularly in nociception. Due to their involvement in key physiological processes, ASICs have emerged as promising targets for the modulation of pain perception. Postoperative pain management is primarily dependent on pharmacological agents, such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), to alleviate discomfort and facilitate recovery. However, the long-term use of these analgesics is associated with significant risks, including opioid dependence, tolerance, and other adverse effects. As such, the development of non-pharmacological alternatives for pain management is critically needed. Modulating ASIC activity offers a compelling approach to attenuate pain perception, providing an opportunity to reduce reliance on traditional pharmacological agents and their associated side effects. This highlights the importance of further research into ASICs as therapeutic targets for pain management, which could revolutionize postoperative care by offering safer and more effective pain relief strategies.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"18 1","pages":"8-16"},"PeriodicalIF":0.0,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative study of artifact reduction techniques in metal-implanted CT scans.","authors":"Diana Rafieezadeh, Amirreza Khalaji, Ava Goli, Ali Gharavinia, Hossein Mohammadi","doi":"10.62347/GFJJ2560","DOIUrl":"10.62347/GFJJ2560","url":null,"abstract":"<p><p>Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"18 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analgesic effect of intravenous nefopam for postoperative pain in spine surgery: a meta-analysis of RCTs.","authors":"Muhammad Parsa Pashazadeh, Zhale Nahavandi, Arad Ghorbani, Shahan Shakeri, Mina Abbasi, Sepehr Haghshoar, Shiva Sayedsalehi, Omid Salimi, Vida Hafezi, Yaser Khakpour, Zahra Farrokhi, Mahdyieh Naziri, Haleh Alizadeh, Niloofar Deravi","doi":"10.62347/LVMJ6188","DOIUrl":"10.62347/LVMJ6188","url":null,"abstract":"<p><strong>Background and objective: </strong>For the management of postoperative pain, opioids have typically been half their efficacy, but they are associated with notable side effects such as sedation, nausea, and respiratory depression. Nefopam is a non-opioid analgesic, within the benzoxazocine class, that has been suggested as an important adjunctive analgestic in multimodal analgesia (MMA). However, the extent to which analgesics outside of opioids are accepted as part of Enhanced Recovery After Surgery (ERAS) programs is controversial. The difficulty of predicting pain management outcome, considering the variability in postoperative pain, means that study of the analgesic effect of intravenous nefopam given different strategies, is essential in the use of nefopam for spinal surgery.</p><p><strong>Methods: </strong>We completed a systematic search of PubMed, Scopus, and Google Scholar until July 20, 2025. We included randomized controlled trials (RCTs) that assessed intravenous nefopam for treating postoperative pain in patients who had spine surgery. The extracted data were pooled, and we performed a random-effects meta-analysis. Subgroup analyses were planned to compare bolus use, infusion use, and bolus plus infusion use.</p><p><strong>Results: </strong>Seven RCTs, involving a total of 471 patients, were included in the eligibility criteria. The overall pooled analysis found no differences in postoperative pain scores between the nefopam and control conditions. The standardized mean difference (SMD) was -0.28 (95% confidence interval [CI]: -0.74 to 0.18), which indicated no difference in efficacy. The sub-group analysis found that bolus administration had the greatest analgesic effect (SMD = -0.70) and infusion or bolus + infusions had little or no clinical benefit. The infusion sub-group had the greatest heterogeneity (I² = 86.9%) suggesting variability in studies for this delivery method.</p><p><strong>Conclusion: </strong>The use of intra-venous nefopam offers a small analgesic benefit in spine surgery, which is best seen when applied intermittently or as a bolus rather than as a continuous infusion. Though it is not particularly effective as a standalone agent, bolus does have potential as an adjunct and should be included as part of a more multimodal analgesia approach. Further high quality RCTs with larger sample sizes are warranted to better define the optimal application of nefopam and dosing in patients undergoing spinal surgery.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 6","pages":"177-187"},"PeriodicalIF":0.0,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bupivacaine with methylprednisolone in ESP block reduces postoperative pain and opioid consumption after lumbar spine surgery.","authors":"Masoud Nashibi, Parisa Sezari, Farhad Safari, Arash Aziznezhad, Ali Kheiandish, Saleh Shahsavari, Hasanali Ahmadi, Atieh Sadat Moosavi Tarshizi, Niloofar Deravi, Sogol Asgari","doi":"10.62347/YWWO8879","DOIUrl":"10.62347/YWWO8879","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pain management in spine surgery is challenging. While opioids are effective, their significant adverse effects, including respiratory depression, necessitate opioid-sparing strategies. The Erector Spinae Plane (ESP) block has emerged as a promising regional technique. This study investigates whether the addition of methylprednisolone to bupivacaine in an ESP block enhances postoperative analgesia and reduces opioid consumption in patients undergoing lumbar spine surgery.</p><p><strong>Method: </strong>This prospective, randomized clinical trial (Ethical Approval ID: IR.SBMU.RETECH.REC.1403.467) included 64 patients (18-65 years) for two- or three-level lumbar spine surgery. Patients were randomized into two groups: the control group (bupivacaine alone) and the intervention group (bupivacaine combined with methylprednisolone). Data were collected on intraoperative metrics (e.g., fluid therapy, blood loss, operation time), opioid consumption, postoperative pain scores (NRS), incidence of nausea and shivering, blood glucose levels, and need for rescue analgesia up to one month post-surgery.</p><p><strong>Results: </strong>The methylprednisolone group showed significantly lower narcotics consumption (intraoperatively and in the PACU). The pain level (NRS) was also lower in this group for up to four weeks post-operation. There were no significant inter-group differences in surgery duration, anesthetic consumption, bleeding, or the incidence of nausea and chills.</p><p><strong>Conclusion: </strong>The use of methylprednisolone as an adjuvant to bupivacaine in the ESP block improves the quality and duration of analgesia in spine surgery patients. However, the transient elevation in blood glucose levels highlights the need for careful glucose monitoring.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 5","pages":"169-176"},"PeriodicalIF":0.0,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dual role of SGLT2 inhibitors: glycemic control and cardioprotection in anthracycline-treated cancer patients.","authors":"Azad Mojahedi","doi":"10.62347/GAXZ3059","DOIUrl":"10.62347/GAXZ3059","url":null,"abstract":"<p><p>Anthracyclines are vital chemotherapy drugs for treating various cancers, including solid tumors and blood cancers; however, they cause dose-dependent cardiotoxicity, manifesting as cardiomyopathy, arrhythmias, and heart failure (HF). Cardiotoxicity, driven by oxidative stress, mitochondrial dysfunction, and other mechanisms, limits its use and affects long-term patient outcomes. Meanwhile, sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed for type 2 diabetes, offer cardiovascular benefits beyond glucose control, such as reduced HF hospitalization and mortality. These benefits stem from improved myocardial energetics, reduced fibrosis, and improved regulation of cardiac ion homeostasis. Experimental studies, including animal models, have shown that SGLT2 inhibitors, such as empagliflozin, preserve cardiac function and reduce inflammation in anthracycline-induced cardiotoxicity. Clinical data, although limited to small retrospective studies, suggest lower mortality and fewer cardiovascular events in anthracycline-treated cancer patients using SGLT2 inhibitors. However, variability in the study design highlights the need for a systematic evaluation. This systematic review aimed to critically assess the cardiovascular outcomes associated with SGLT2 inhibitor use in cancer patients treated with anthracyclines, evaluating their dual role in glycemic control and cardioprotection, and to identify evidence gaps to inform therapeutic strategies for optimizing long-term cardiovascular health in this vulnerable population.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 5","pages":"158-168"},"PeriodicalIF":0.0,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-N-acetylgalactosaminidase in cancer: diagnostic applications and related treatment strategies.","authors":"Fatemeh Keshmiri, Somayeh Ghavidel Yazdi, Hadis Pazhohan-Nezhad, Manouchehr Teymouri, Farzaneh Alizadeh, Ehsan Saburi","doi":"10.62347/WSHW8932","DOIUrl":"10.62347/WSHW8932","url":null,"abstract":"<p><p>Alpha-N-acetylgalactosaminidase (nagalase), a lysosomal enzyme encoded by the NAGA gene, plays a critical role in the degradation of glycoconjugates, modulation of immune responses, and regulation of vitamin D metabolism. Dysregulation of nagalase is associated with several pathological conditions, including Schindler disease, psychiatric disorders, viral infections, and notably, cancer. Elevated serum levels of nagalase, particularly the Naga6 isoform, have been observed in cancer patients and individuals with enveloped viral infections, contributing to immune evasion by impairing macrophage activation through Gc protein deglycosylation. Moreover, nagalase activity has been implicated in rare blood group changes observed in some malignancies. Although ELISA-based assays offer potential for quantifying nagalase, their clinical application is hindered by assay interferences and cross-reactivity. The immunotherapeutic potential of Gc protein-derived macrophage activating factor (GcMAF), in combination with vitamin D3 and ascorbate, has shown promise in enhancing anti-tumor immunity, particularly in prostate cancer. Nevertheless, conflicting data and methodological criticisms have led to skepticism regarding its efficacy. This review comprehensively explores the biochemical variants of nagalase, its physiological and pathological roles, its diagnostic utility as a biomarker, and emerging therapeutic strategies targeting its activity, including gene silencing and monoclonal antibody development. The findings underscore the need for rigorous clinical studies to validate the diagnostic and therapeutic potential of nagalase in oncology and immunology.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 4","pages":"104-115"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using ultrasonographic features in pediatric Crohn's disease activity index severity.","authors":"Maryam Riahinezhad, Fereshteh Sharifi Dorcheh, Hosein Saneian, Fatemeh Khounsarian","doi":"10.62347/RIGM1803","DOIUrl":"10.62347/RIGM1803","url":null,"abstract":"<p><strong>Background: </strong>The diagnosis and follow-up of Crohn's disease (CD) often require invasive instrumental examinations, which carry a high risk of iatrogenic injury. This study aimed to determine the frequency of ultrasound features in each stage of the Pediatric Crohn's Disease Activity Index (PCDAI).</p><p><strong>Methods: </strong>This cross-sectional study included 22 pediatric patients with Crohn's disease. Disease activity was assessed using the PCDAI. The state of CD activity was categorized into four groups: remission (PCDAI scores less than 10), mild (PCDAI scores of 10-27.5), moderate (PCDAI scores of 30-37.5), and severe (PCDAI scores > 40). Clinical data collected included the thickness of the ascending colon loop, the thickness of the ileal loop, the number of lymph nodes, the short-axis diameter of lymph nodes (mm), spleen span, presence of free fluid, fistulas, liver echogenicity, vascularity around the loops, lumen narrowing, terminal ileum compression, mesenteric fat hypertrophy, intestinal wall and mesenteric fat echogenicity, and Superior Mesenteric Artery indices. These data were documented for analysis.</p><p><strong>Results: </strong>As disease activity progressed from mild to severe, intestinal wall echogenicity, fat echogenicity, mesenteric fat, vascularity, and lumen narrowing significantly increased (P < 0.05). The mean ileal loop thickness also significantly increased (P = 0.005), rising from 2.12 ± 0.58 in mild cases to 4.49 ± 1.43 in severe cases. However, the mean ascending colon loop thickness, the number of lymph nodes, the short-axis diameter of lymph nodes, and spleen span were not statistically significant (P > 0.05). Changes in the superior mesenteric artery indices across the different PCDAI phases were also not statistically significant (P > 0.05).</p><p><strong>Conclusions: </strong>Ultrasound is a convenient and reproducible tool for monitoring CD activity in pediatrics. This study demonstrated significant findings, including the increase in intestinal wall echogenicity, fat echogenicity, mesenteric fat hypertrophy, vascularity, and lumen narrowing as the disease activity progressed from mild to severe. Particularly, the mean ileal loop thickness showed a significant increase in the severe phase compared to the mild phase.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 4","pages":"148-157"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An updated meta-analysis on the efficacy and safety of medications administered after non-surgical root canal treatment in managing postoperative pain.","authors":"Dorsa Samani, Armin Arian, Kimia Kelidari, Mahsa Moosapoor Farkhani, Aida Keshavarzi, Kimia Sadat Kazemi, Sepehr Haghshoar, Sharare Jahangiri, Fereshteh Molaei, Sahar Rajaei, Haleh Fakhimi Rezaei, Sina Ahmadi, Mohaddeseh Belbasi, Alireza Mokhtari Sakhvidi, Mahdyieh Naziri","doi":"10.62347/RHSD5636","DOIUrl":"10.62347/RHSD5636","url":null,"abstract":"<p><p>Effective management is one of the most important factors in mitigating postoperative endodontic pain (PEP). The purpose of this network meta-analysis was to compare the therapeutic effects and safety of different drugs commonly used for pain relief after non-surgical endodontic treatment. We searched the Scopus, PubMed, and Google Scholar databases until February 2024. Titles, abstracts, and full texts were identified according to predetermined criteria. Data were extracted from the selected publications, and a quality assessment was performed for the included studies. Sixteen RCTs with 2,021 participants were included in the meta-analysis. All included studies investigated the impact of NSAIDs on pain reduction in nonsurgical endodontic treatment. A statistically significant reduction in pain was observed at 8 h (pooled effect = -3.10, I² = 100%), 12 h (pooled effect = -1.69, I² = 99.2%), 24 h (pooled effect = -1.48, I² = 99.9%), 48 h (pooled effect = -1.42, I² = 99.4%), and 72 h (pooled effect = -0.64, I² = 73.1%) of follow-up. The funnel plot was symmetrical, and sensitivity analysis excluded one article in 72 h follow-up. Overall, this meta-analysis demonstrated that NSAIDs and corticostreoids are statistically effective in relieving pain after non-surgical endodontic treatment. However, owing to the significant differences between studies and heterogenicity, additional randomized controlled trials are needed to validate this correlation further.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 4","pages":"116-130"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formoterol promotes mitochondrial biogenesis, improves liver regeneration, and suppresses liver injury and inflammation after liver resection in mice with endotoxemia.","authors":"Amir K Richardson, Devadoss J Samuvel, Yasodha Krishnasamy, John J Lemasters, Zhi Zhong","doi":"10.62347/JMWH4994","DOIUrl":"10.62347/JMWH4994","url":null,"abstract":"<p><strong>Objectives: </strong>Clinically, liver regeneration is often impaired by infections causing endotoxemia, although mechanisms are unclear. Since energy supply is essential for liver regeneration, we assessed whether formoterol (FMT), a β₂-adrenergic agonist that increases peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), the master regulator of mitochondrial biogenesis (MB), restores liver regeneration after partial hepatectomy (PHX) in endotoxin (LPS)-treated mice.</p><p><strong>Methods: </strong>Mice underwent sham-operation, two-thirds PHX, PHX with LPS injection (PHX+LPS, 5 mg/kg, <i>i.p.</i>), or PHX+LPS followed by FMT (0.1 mg/kg, <i>i.p.</i>) after 2 h.</p><p><strong>Results: </strong>At 48 h after PHX, 5'-bromo-2'-deoxyuridine incorporation, mitotic cells, proliferating cell nuclear antigen, and cyclin-D1 markedly increased, signifying liver regeneration. By contrast, after PHX+LPS, liver regeneration was almost completely suppressed. FMT restored liver regeneration after PHX+LPS. PGC1α, mitochondrial transcription factor-A (controlling mitochondrial DNA replication/transcription), and mitochondrial oxidative phosphorylation proteins ATP synthase-β and NADH dehydrogenase-3 decreased after PHX+LPS, signifying suppressed MB. FMT largely reversed these effects. Mitochondrial oxidative stress stimulates inflammation by activating inflammasomes. In addition to promoting MB, PGC1α reportedly inhibits oxidative stress and inflammation. 8-Hydroxy-deoxyguanosine, NLRP3, and inflammatory cytokines increased after PHX+LPS, demonstrating increased oxidative stress and inflammasome activation. Many necro-inflammatory foci occurred in liver sections after PHX+LPS. FMT increased expression of antioxidant protein thioredoxin-2, decreased oxidative stress, and blunted inflammatory responses. Additionally, FMT decreased alanine aminotransferase release and necrosis caused by PHX+LPS.</p><p><strong>Conclusions: </strong>FMT restores liver regeneration during endotoxemia and decreases liver injury and inflammation, most likely by increasing PGC1α. Therefore, FMT is a promising therapy for liver failure caused by loss of liver mass complicated with sepsis.</p>","PeriodicalId":94056,"journal":{"name":"International journal of physiology, pathophysiology and pharmacology","volume":"17 4","pages":"131-147"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}