The Kaohsiung journal of medical sciences最新文献

{"title":"Complement factor B inhibitor LNP023 mediates the effect and mechanism of AMPK/mTOR on autophagy and oxidative stress in lupus nephritis.","authors":"Xi-Mei Zhang, Ming-Jie Qing, Xin-Kuo Liu, Liang Peng","doi":"10.1002/kjm2.12894","DOIUrl":"10.1002/kjm2.12894","url":null,"abstract":"<p><p>This study investigated the impact of LNP023 on the AMPK/mTOR signaling pathway in lupus nephritis (LN) and its effects on autophagy and oxidative stress. A mouse model of LN was established, and renal injury was confirmed by assessing various LN markers, including antinuclear antibody, ds-DNA, anti-Sm antibody, and others. Mice were treated with LNP023, the AMPK activator AICAR, or the AMPK inhibitor dorsomorphin. Renal injury and fibrosis were evaluated using HE and Masson staining. Expression levels of AMPK, mTOR, LC3, Beclin1, and p62 were assessed by immunohistochemistry and Western blot. Oxidative stress and inflammatory markers were measured by polymerase chain reaction and enzyme-linked immunosorbent assay. LN mice exhibited low AMPK/p-AMPK and high mTOR/p-mTOR levels, alongside significant renal injury, fibrosis, reduced autophagy, and elevated oxidative stress. LNP023 treatment improved these parameters, with enhanced effects when combined with AICAR. Conversely, dorsomorphin reversed LNP023's therapeutic benefits. The complement factor B inhibitor LNP023 promotes kidney health in LN mice by mediating the AMPK/mTOR pathway, promoting autophagy, and attenuating oxidative stress.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"996-1005"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484783","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":"Long non-coding RNA MALAT1 triggers ferroptosis via interaction with FUS to enhance ACSF2 mRNA stabilization in septic acute kidney injury.","authors":"Zhi-Bing Duan, Ji-Fu Zheng, Si-Yue Huang, Li-Li Hu","doi":"10.1002/kjm2.12898","DOIUrl":"10.1002/kjm2.12898","url":null,"abstract":"<p><p>Septic acute kidney injury (AKI) is a fatal disease in the intensive care unit, with ferroptosis playing a crucial role in its pathogenesis. Long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in septic-induced AKI inflammation and apoptosis. However, its regulatory role in ferroptosis and underlying mechanisms remain unclear. In vivo and in vitro models of septic AKI were established using cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) challenge, respectively. Serum levels of creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), and inflammatory cytokine in kidney tissues were determined by ELISA kits. Histopathological alterations and apoptosis were evaluated by HE staining and TUNEL. Ferroptosis was accessed by measuring MDA, GSH, Fe²⁺, total and lipid ROS levels, and mitochondrial ultrastructure changes. Target molecular levels were determined using RT-qPCR, Western blotting, and immunofluorescence. Interactions among MALAT1, acyl-CoA synthetase family member 2 (ACSF2) and FUS RNA binding protein (FUS) were validated by RIP and RNA-pull down. MALAT1 level was significantly elevated in both in vivo and in vitro septic AKI models, of which knockdown impeded ferroptosis to alleviate septic AKI. Mechanistically, high MALAT1 expression increased ACSF2 mRNA stability via interaction with FUS. Rescue experiments showed that ACSF2 overexpression partially reversed the ferroptosis inhibition mediated by MALAT1 silencing. MALAT1 induces ferroptosis and exacerbates septic AKI by stabilizing ACSF2 mRNA with the assistance of FUS. These findings provide theoretical evidence for MALAT1 as a potential therapeutic target for septic AKI.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"972-984"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402608","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":"Berberine safeguards sepsis-triggered acute gastric damage and inhibits pyroptosis in gastric epithelial cells via suppressing the ubiquitination and degradation of Nrf2.","authors":"Shu-Rui Xie, Yan-Jun Liu, Fen-Qiao Chen, Zhao Pan","doi":"10.1002/kjm2.12900","DOIUrl":"10.1002/kjm2.12900","url":null,"abstract":"<p><p>Berberine (BBR), a widely recognized traditional Chinese medicine, has attracted considerable attention for its promising anti-inflammatory effects. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) effectively safeguards against organ damage stemming from sepsis-induced oxidative stress and inflammatory responses. This study examined the potential of BBR in alleviating sepsis-induced acute gastric injury, with a particular focus on elucidating whether its mechanism of action involves the activation of the Nrf2 signaling pathway. Following intraperitoneal injection of BBR, mice were subjected to the cecal ligation and puncture (CLP) method to induce sepsis. In vitro experiments involved pre-treating the normal gastric epithelial cells (GES-1) with BBR, followed by treatment with lipopolysaccharide (LPS). Functional assays were then performed to assess cell proliferation and apoptosis. To validate the role of Nrf2 in pyroptosis and inflammation, siRNA targeting Nrf2 (si-Nrf2) was transfected into LPS-treated GES-1 cells. Additionally, mice were administered the Nrf2 inhibitor ML385 to confirm the protective effects of BBR in vivo. BBR displayed a dose-dependent effect in mitigating gastric tissue damage, suppressing the release of inflammatory cytokines, and reducing the expression of NLRP3, ASC, and GSDMD-N. In vitro, BBR fostered GES-1 cell proliferation, hindered apoptosis, and suppressed the levels of TNF-α, IL-18, IL-1β, NLRP3, ASC, and GSDMD-N. Further analysis revealed that knocking down Nrf2 reversed BBR's inhibitory effect on pyroptosis in LPS-treated GES-1 cells. Through binding to Keap1, BBR efficiently prevented the ubiquitination and degradation of Nrf2, ultimately promoting its nuclear translocation. In vivo experiments confirmed that ML385 reversed the protective effect of BBR on pyroptosis and inflammation. Our research reveals that BBR interacts with Keap1 to activate the Keap1/Nrf2 signaling pathway in gastric epithelial cells, thereby suppressing pyroptosis and inflammation in sepsis-induced acute gastric injury.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"1006-1019"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559927","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":"Prediction model of in-hospital cardiac arrest using machine learning in the early phase of hospitalization.","authors":"Wei-Tsung Wu, Chew-Teng Kor, Ming-Chung Chou, Hui-Min Hsieh, Wan-Chih Huang, Wei-Ling Huang, Shu-Yen Lin, Ming-Ru Chen, Tsung-Hsien Lin","doi":"10.1002/kjm2.12895","DOIUrl":"10.1002/kjm2.12895","url":null,"abstract":"<p><p>In hospitals, the deterioration of a patient's condition leading to death is often preceded by physiological abnormalities in the hours to days beforehand. Several risk-scoring systems have been developed to identify patients at risk of major adverse events; however, such systems often exhibit low sensitivity and specificity. To identify the risk factors associated with in-hospital cardiac arrest (IHCA), we conducted a retrospective cohort study at a tertiary medical center in Taiwan. Four machine learning algorithms were employed to identify the factors most predictive of IHCA. The support vector machine model was discovered to be the most effective at predicting IHCA. The ten most critical physiological parameters at 8 h prior to the event were pulse rate, age, white blood cell count, lymphocyte count, body temperature, body mass index, systolic and diastolic blood pressure, platelet count, and use of central nervous system-active medication. Using these parameters, we can enhance early warning and rapid response systems in our hospital, potentially reducing the incidence of IHCA in clinical practice.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"1029-1035"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335612","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":"The role of artificial intelligence in the management of liver diseases.","authors":"Ming-Ying Lu, Wan-Long Chuang, Ming-Lung Yu","doi":"10.1002/kjm2.12901","DOIUrl":"10.1002/kjm2.12901","url":null,"abstract":"<p><p>Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct-acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost-effective identification of high-risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high-throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non-linear data and identify hidden patterns within real-world datasets. The combination of AI and multi-omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non-invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision-making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"962-971"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515687","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":"Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR-149-3p/AKT1 axis.","authors":"Dan Wang, Xin-Rui Zhao, Yi-Fan Li, Rui-Lin Wang, Xue-Bing Li, Chun-Xia Wang, Yong-Wei Li","doi":"10.1002/kjm2.12887","DOIUrl":"10.1002/kjm2.12887","url":null,"abstract":"<p><p>Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"903-915"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006251","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":"Multiple intracerebral hemorrhages secondary to eosinophilic granulomatosis with polyangiitis: A case report and literature review.","authors":"Guo Li, Xing-Ren Liu, Ling-Jing Yang","doi":"10.1002/kjm2.12882","DOIUrl":"10.1002/kjm2.12882","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"949-950"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001671","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":"Relevance of ineffective esophageal motility to striated esophageal muscle contraction: Studies with high-resolution manometry.","authors":"Jui-Sheng Hung, Wei-Yi Lei, Ming-Wun Wong, Chih-Hsun Yi, Tso-Tsai Liu, Chien-Lin Chen","doi":"10.1002/kjm2.12884","DOIUrl":"10.1002/kjm2.12884","url":null,"abstract":"<p><p>Striated esophageal muscle contraction (SEC) is important for pharyngeal swallowing and deglutition augmentation against aspiration. Its clinical relevance is unclear in patients with ineffective esophageal motility (IEM). In this study, we aimed to characterize and compare SEC in consecutive patients with and without IEM. All eligible patients were evaluated for SEC, primary and secondary peristalsis using high-resolution manometry (HRM) with one mid-esophageal injection port. Primary peristalsis was assessed with 10 5-mL liquid swallows and multiple rapid swallows (MRS), while secondary peristalsis was performed with rapid air injections of 20 mL. All peristatic parameters of HRM were measured, and SEC and its contractile integral (SECI) were evaluated. One hundred and forty patients (59.3% women, mean age 46.1 ± 13.1 years) were included. There was no difference in SECI between patients with and without IEM (p = 0.91). SECI was also similar between patients with and without secondary peristalsis for IEM (p = 0.63) or normal motility (p = 0.80). No difference in SECI was seen between patients with and without MRS for IEM (p = 0.55) or normal motility (p = 0.88). SECI was significantly higher in male patients than female patients in IEM patients (p = 0.01). SECI significantly correlated with age in patients with normal motility (r = -0.31, p = 0.01). Aging may have a negative impact on SEC in patients with normal motility, while gender difference in SECI occurs in IEM patients. Neither secondary peristalsis nor MRS influences SECI.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"942-946"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862000","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":"Unusual leonine facies: A rare presentation.","authors":"Jiong-Huang Lim, Feng-Ling Lin","doi":"10.1002/kjm2.12881","DOIUrl":"10.1002/kjm2.12881","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"951-952"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790705","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":"CD276 is a promising biomarker for the prognosis of clear cell renal cell carcinoma.","authors":"Yan-Hang Yu, Jian-Hao Xu, Hao Chen, Yu-Xin Lin, Jun Ou-Yang, Zhi-Yu Zhang","doi":"10.1002/kjm2.12891","DOIUrl":"10.1002/kjm2.12891","url":null,"abstract":"<p><p>This study aimed to investigate the role of cluster of differentiation 276 (CD276) in evaluating the prognosis of clear cell renal carcinoma (ccRCC) and to build a nomogram for predicting ccRCC progression post-surgery. Using data downloaded from The Cancer Genome Atlas (TCGA) database, we constructed a Kaplan-Meier (KM) curve depicting the relationship between CD276 expression levels and the progression-free interval (PFI) in 539 ccRCC cases. We further validated this by plotting a KM curve of the relationship between CD276 expression levels and PFI in 116 ccRCC patients from our hospital. Using clinical data collected from 116 patients, we identified independent risk factors affecting postoperative PFI in patients with ccRCC through univariate and multivariate COX analyses and created a nomogram for visual representation. Both TCGA and clinical data revealed a negative correlation between the expression levels of CD276 and PFI (p < 0.05). Univariate COX analysis revealed that the prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, World Health Organization grading, tumor diameter, CD276 expression levels, T stage, and N stage were related to PFI (p < 0.05). Furthermore, multivariate COX analysis indicated that tumor diameter and CD276 expression levels were independent risk factors for postoperative PFI in patients with ccRCC (p < 0.05). The calibration curve of the established nomogram exhibited a slope close to 1, with a Hosmer-Lemeshow goodness-of-fit test result of 2.335 and a p-value of 0.311. In patients with ccRCC, a negative correlation was noted between tumor CD276 expression and PFI. The larger the tumor diameter and the higher the tumor CD276 expression level, the shorter is the PFI.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"926-933"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116703","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}