Background: Nonalcoholic fatty liver disease, a progressive condition caused by the accumulation of fat in the liver, begins with simple steatosis and can potentially progress to metabolic dysfunction-associated steatohepatitis (MASH) in the presence of inflammation and fibrosis, ultimately leading to cirrhosis or hepatocellular carcinoma. Increasing evidence indicates that sodiumglucose cotransporter 2 (SGLT2) inhibitors effectively alleviate MASH in mouse models. However, there is a lack of research on the effects of enavogliflozin on liver disease. In the present study, we investigated the effects of SGLT2 inhibitors on MASH induced by a high-fat, high-cholesterol (HFHC) diet in mice. Methods: Male C57BL/6 mice were fed a normal chow diet, HFHC diet, or HFHC diet with enavogliflozin for 12 weeks. LX-2 and HepG2 cells were treated with enavogliflozin in the presence of various pathological stimuli. Results: The HFHC diet induced excessive hepatic lipid accumulation, inflammation, and severe fibrosis. Administration of enavogliflozin not only ameliorated hepatic steatosis and fibrotic conditions but also suppressed the production of inflammatory cytokines. Positive outcomes were also observed in in vitro experiments, where enavogliflozin demonstrated the ability to impede the activation of hepatic stellate cells and alleviate lipid accumulation in hepatocytes. The potential pathway through which enavogliflozin attenuated liver fibrosis development may be associated with the transforming growth factor β1/Smad signaling pathway. Conclusion Our results suggest that enavogliflozin is effective in a mouse model of MASH by attenuating hepatic steatosis, suppressing inflammation, and improving liver fibrosis.

Purpose: Simple virilizing congenital adrenal hyperplasia (SV-CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disease caused by pathogenic variants of the CYP21A2 gene. Children with SV-CAH often experience delayed diagnosis, presenting with pseudo-precocious puberty in males and genital virilization in females. Genotyping is essential for diagnosis, treatment, optimization, and phenotype prediction. This study describes the clinical and genetic characteristics of SV-CAH to guide treatment strategies. Methods: From November 2016 to March 2023, 79 children (accounting for 34.3% of 230 CAH cases in the overall children’s cohort) from 75 families were classified as SV-CAH due to 21-OHD at the Vietnam National Children's Hospital. Forty-three children underwent CYP21A2 mutation analysis using multiplex ligation-dependent probe amplification and complete gene sequencing to detect pathogenic variants. Results: Median age at diagnosis was 4.5 years (interquartile range, 1 day–22.3 years). There were 38.0% males and 62.0% females. The most common symptoms were penile enlargement in males (53.3%) and clitoromegaly (87.8%) in females; the height standard deviation (SD) at diagnosis was 1.90±1.79 SD (-2.02 to 5.43) according to the World Health Organization; and bone age advancement was 4.65±2.59 years. Genetic analysis identified 21 pathogenic variants and 22 genotypes in 43 children. The most common variant was p.I173N (47.7%); the most common genotype was p.I173N/p.I173N (16.3%). Conclusion Children with SV-CAH are often diagnosed late. To avoid that, early genetic analysis should be prioritized, especially for children diagnosed through newborn screening programs. Determining the genotype is crucial for optimizing treatment strategies, ensuring personalized management, and avoiding overtreatment.

Background: Hepatic stellate cells (HSCs) activation is the principal event in the development of liver fibrosis in which succinate-G-protein coupled receptor 91 signaling has recently been shown to be a contributor. Moreover, endoplasmic reticulum (ER) stress has been reported to involve in HSC activation, but its association with succinate in pathogenesis of liver fibrosis remains scarce. In this study, we investigated the role of gemigliptin, an antidiabetic dipeptidyl peptidase-4 inhibitor, in the succinate-induced ER stress and activation of HSCs. Methods: LX-2 cells, the immortalized human HSCs, were treated with succinate and gemigliptin. For animal experiments, C57BL/6N mice were divided into 3 groups: control diet, high-fat high-cholesterol (HFHC) diet, and HFHC diet mixed with gemigliptin. Results: Succinate significantly induced HSC activation and increased expression of inflammatory markers and the increase in the migration of HSCs. The treatment of succinate also caused ER dilation and activated the unfolded protein response signaling as protein kinase RNA-like ER kinase, eIF2alpha, binding immunoglobulin protein, suggesting increasing ER stress in HSCs. All responses of HSCs to succinate were attenuated with the co-treatment of gemigliptin. Moreover, the exposure of HSCs to tunicamycin, an inducer of ER stress, promoted the expression of α-smooth muscle actin, proliferation and migration of HSCs. In vivo, the level of fibrotic and ER stress markers was increased in mice fed with HFHC diet and the administration of gemigliptin improved these changes in HFHC-induced mice. Conclusion This study showed the involvement of ER stress in the activation of succinateinduced LX-2 HSCs and gemigliptin significantly reduced ER stress in HSC activation.Therefore, gemigliptin may become an anti-fibrotic agent and targeting to succinate and ER stress may be a promising therapeutic in the management of liver fibrosis.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: s/Aims: Parenchymal-sparing anatomical hepatectomy (Ps–AH) based on portal ramification of the right anterior section (RAS) is a new technique to avoid unnecessarily transecting too much liver parenchyma, especially in cases of major anatomical hepatectomy. Methods: We prospectively assessed 26 patients with primary hepatic malignancies having undergone major Ps–AH based on portal ramification of the RAS from August 2018 to August 2022 (48 months). The perioperative indications, clinical data, intra-operative index, pathological postoperative specimens, postoperative complications, and follow-up results were retrospectively evaluated. Results: Among the 26 patients analyzed, there was just one case that had intrahepatic cholangiocarcinoma The preoperative level of α– Fetoprotein was 25.2 ng/mL. All cases (100%) had Child–Pugh A liver function preoperatively. The ventral/dorsal RAS was preserved in 19 and 7 patients, respectively. The mean surgical margin was 6.2 mm. The mean surgical time was 228.5 minutes, while the mean blood loss was 255 mL. In pathology, 5 cases (19.2%) had microvascular invasion, and in the group of HCC patients, 92% of all cases had moderate or poor tumor differentiation. Six cases (23.1%) of postoperative complications were graded over III according to the Clavien–Dindo system, including in three patients resistant ascites or intra-abdominal abscess that required intervention. Conclusions Parenchymal-sparing anatomical hepatectomy based on portal ramification of the RAS to achieve R0-resection was safe and effective, with favorable short-term outcomes. This technique can be used widely in clinical practice.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Globally, providing evidence on the economic burden of chronic obstructive pulmonary disease (COPD) is becoming essential as it assists the health authorities to efficiently allocate resources. This study aimed to summarize the literature on economic burden evidence for COPD from 1990 to 2019. This study examined the economic burden of COPD through a systematic review of studies from 1990 to 2019. A search was done in online databases, including Web of Science, PubMed/Medline, Scopus, and the Cochrane Library. After screening 12,734 studies, 43 articles that met the inclusion criteria were identified. General study information and data on direct, indirect, and intangible costs were extracted and converted to 2018 international dollars (Int$). Findings revealed that the total direct costs ranged from Int$ 52.08 (India) to Int$ 13,776.33 (Canada) across 16 studies, with drug costs rannging from Int$ 70.07 (Vietnam) to Int$ 8,706.9 (China) in 11 studies. Eight studies explored indirect costs, while one highlighted caregivers’ direct costs at approximately Int$ 1,207.8 (Greece). This study underscores the limited research on COPD caregivers’ economic burdens, particularly in developing countries, emphasizing the importance of increased research support, particularly in high-resource settings. This study provides information about the demographics and economic burden of COPD from 1990 to 2019. More strategies to reduce the frequency of hospital admissions and acute care services should be implemented to improve the quality of COPD patients’ lives and reduce the disease’s rising economic burden.

Background: Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study. Methods: In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver. Results: Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis. Conclusion Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.