Current Evidence and Perspectives of Cluster of Differentiation 44 in the Liver's Physiology and Pathology.

Cluster of differentiation 44 (CD44), a multi-functional cell surface receptor, has several variants and is ubiquitously expressed in various cells and tissues. CD44 is well known for its function in cell adhesion and is also involved in diverse cellular responses, such as proliferation, migration, differentiation, and activation. To date, CD44 has been extensively studied in the field of cancer biology and has been proposed as a marker for cancer stem cells. Recently, growing evidence suggests that CD44 is also relevant in non-cancer diseases. In liver disease, it has been shown that CD44 expression is significantly elevated and associated with pathogenesis by impacting cellular responses, such as metabolism, proliferation, differentiation, and activation, in different cells. However, the mechanisms underlying CD44's function in liver diseases other than liver cancer are still poorly understood. Hence, to help to expand our knowledge of the role of CD44 in liver disease and highlight the need for further research, this review provides evidence of CD44's effects on liver physiology and its involvement in the pathogenesis of liver disease, excluding cancer. In addition, we discuss the potential role of CD44 as a key regulator of cell physiology.

Tumor necrosis factor-inducible gene 6 protein and its derived peptide ameliorate liver fibrosis by repressing CD44 activation in mice with alcohol-related liver disease.

BACKGROUND: Alcohol-related liver disease (ALD) is a major health concern worldwide, but effective therapeutics for ALD are still lacking. Tumor necrosis factor-inducible gene 6 protein (TSG-6), a cytokine released from mesenchymal stem cells, was shown to reduce liver fibrosis and promote successful liver repair in mice with chronically damaged livers. However, the effect of TSG-6 and the mechanism underlying its activity in ALD remain poorly understood. METHODS: To investigate its function in ALD mice with fibrosis, male mice chronically fed an ethanol (EtOH)-containing diet for 9 weeks were treated with TSG-6 (EtOH + TSG-6) or PBS (EtOH + Veh) for an additional 3 weeks. RESULTS: Severe hepatic injury in EtOH-treated mice was markedly decreased in TSG-6-treated mice fed EtOH. The EtOH + TSG-6 group had less fibrosis than the EtOH + Veh group. Activation of cluster of differentiation 44 (CD44) was reported to promote HSC activation. CD44 and nuclear CD44 intracellular domain (ICD), a CD44 activator which were upregulated in activated HSCs and ALD mice were significantly downregulated in TSG-6-exposed mice fed EtOH. TSG-6 interacted directly with the catalytic site of MMP14, a proteolytic enzyme that cleaves CD44, inhibited CD44 cleavage to CD44ICD, and reduced HSC activation and liver fibrosis in ALD mice. In addition, a novel peptide designed to include a region that binds to the catalytic site of MMP14 suppressed CD44 activation and attenuated alcohol-induced liver injury, including fibrosis, in mice. CONCLUSIONS: These results demonstrate that TSG-6 attenuates alcohol-induced liver damage and fibrosis by blocking CD44 cleavage to CD44ICD and suggest that TSG-6 and TSG-6-mimicking peptide could be used as therapeutics for ALD with fibrosis.

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress.

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Depolymerized Chitosan-g-[Poly(MMA-co-HEMA-cl-EGDMA)] Based Nanogels for Controlled Local Release of Bupivacaine.

This study is designed to formulate and characterize chitosan-based nanogels that provide the controlled delivery of anesthetic drugs, such as bupivacaine (BPV), for effective postoperative pain management over prolonged periods of time. Drug carriers of chitosan/poly (MMA-co-HEMA-cl-EGDMA) (CsPMH) nanogels were prepared by varying the composition of comonomers such as MMA, HEMA, and redox initiator CAN. The nanogels were then characterized using FTIR, TGA, SEM, and TEM. The CsPMH nanogels showed greater encapsulation efficiencies from 43.20-91.77%. Computational studies were also conducted to evaluate the interaction between the drug and CsPMH nanoparticles. Finally, BPV-loaded nanoparticles were used to examine their in vitro release behavior. At pH 7.4, all the drug carriers displayed the "n" value around 0.7, thus the BPV release follows anomalous diffusion. Drug carrier 7 demonstrated a steady and sustained release of BPV for approximately 24 h and released about 91% of BPV, following the K-P mechanism of drug release. On the other hand, drug carrier 6 exhibited controlled release for approximately 12 h and released only 62% of BPV.

Therapeutic strategies to improve liver regeneration after hepatectomy.

Chronic liver disease is one of the most common diseases worldwide, and its prevalence is particularly high among adults aged 40-60 years; it takes a toll on productivity and causes significant economic burden. However, there are still no effective treatments that can fundamentally treat chronic liver disease. Although liver transplantation is considered the only effective treatment for chronic liver disease, it has limitations in that the pool of available donors is vastly insufficient for the number of potential recipients. Even if a patient undergoes liver transplantation, side effects such as immune rejection or bile duct complications could occur. In addition, impaired liver regeneration due to various causes, such as aging and metabolic disorders, may cause liver failure after liver resection, even leading to death. Therefore, further research on the liver regeneration process and therapeutic strategies to improve liver regeneration are needed. In this review, we describe the process of liver regeneration after hepatectomy, focusing on various cytokines and signaling pathways. In addition, we review treatment strategies that have been studied to date to improve liver regeneration, such as promotion of hepatocyte proliferation and metabolism and transplantation of mesenchymal stem cells. This review helps to understand the physiological processes involved in liver regeneration and provides basic knowledge for developing treatments for successful liver regeneration.

Targeted Deletion of Thymosin Beta 4 in Hepatic Stellate Cells Ameliorates Liver Fibrosis in a Transgenic Mouse Model.

Liver fibrosis is the most common feature of liver disease, and activated hepatic stellate cells (HSCs) are the main contributors to liver fibrosis. Thus, finding key targets that modulate HSC activation is important to prevent liver fibrosis. Previously, we showed that thymosin ß4 (Tß4) influenced HSC activation by interacting with the Hedgehog pathway in vitro. Herein, we generated Tß4 conditional knockout (Tß4-flox) mice to investigate in vivo functions of Tß4 in liver fibrosis. To selectively delete Tß4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tß4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ERT2 mice, and these mice were administered carbon tetrachloride (CCl4) or underwent bile duct ligation to induce liver fibrosis. Tß4 was selectively suppressed in the activated HSCs of DTG mouse liver, and this reduction attenuated liver injury, including fibrosis, in both fibrotic models by repressing Hedgehog (Hh) signaling. In addition, the re-expression of Tß4 by an adeno-associated virus reversed the effect of HSC-specific Tß4 deletion and led to liver fibrosis with Hh activation in CCl4-exposed mice treated with tamoxifen. In conclusion, our results demonstrate that Tß4 is a crucial regulator of HSC activation, suggesting it as a novel therapeutic target for curing liver fibrosis.

N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis.

As our previous study revealed that N-benzyl-N-methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum, exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1ß production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase (MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA.

Formyl peptide receptor 2 is an emerging modulator of inflammation in the liver.

Formyl peptide receptors (FPRs), which are seven-membrane G-protein coupled receptors, recognize chemotactic signals to protect hosts from pathogenic infections and mediate inflammatory responses in the body. There are three isoforms of FPRs in humans-FPR1, FPR2, and FPR3-and they bind to N-formyl peptides, except FPR3, and to various endogenous agonists. Among FPR family members, FPR2 has a lower affinity for N-formyl peptides than FPR1 and binds with a wide range of endogenous or exogenous agonists. Thus, FPR2 is considered the most ambiguous member. Accumulating evidence has shown that FPR2 is involved in the host's defense against bacterial infection and inflammation in liver diseases, such as nonalcoholic fatty liver disease, liver fibrosis, and liver cancer, suggesting the pathophysiological relevance of FPR2 to the liver. However, FPR2 has been shown to promote or suppress inflammation, depending on the type of FPR2-expressing cell and FPR2-bound ligands in the liver. Therefore, it is important to understand FPR2's function per se and to elucidate the mechanism underlying immunomodulation initiated by ligand-activated FPR2 before suggesting FPR2 as a novel therapeutic agent for liver diseases. In this review, up-to-date knowledge of FPR2, with general information on the FPR family, is provided. We shed light on the dual action of FPR2 in the liver and discuss the hepatoprotective roles of FPR2 itself and FPR2 agonists in mediating anti-inflammatory responses.

Prediction of Clinical Remission with Adalimumab Therapy in Patients with Ulcerative Colitis by Fourier Transform-Infrared Spectroscopy Coupled with Machine Learning Algorithms.

We aimed to develop prediction models for clinical remission associated with adalimumab treatment in patients with ulcerative colitis (UC) using Fourier transform-infrared (FT-IR) spectroscopy coupled with machine learning (ML) algorithms. This prospective, observational, multicenter study enrolled 62 UC patients and 30 healthy controls. The patients were treated with adalimumab for 56 weeks, and clinical remission was evaluated using the Mayo score. Baseline fecal samples were collected and analyzed using FT-IR spectroscopy. Various data preprocessing methods were applied, and prediction models were established by 10-fold cross-validation using various ML methods. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed a clear separation of healthy controls and UC patients, applying area normalization and Pareto scaling. OPLS-DA models predicting short- and long-term remission (8 and 56 weeks) yielded area-under-the-curve values of 0.76 and 0.75, respectively. Logistic regression and a nonlinear support vector machine were selected as the best prediction models for short- and long-term remission, respectively (accuracy of 0.99). In external validation, prediction models for short-term (logistic regression) and long-term (decision tree) remission performed well, with accuracy values of 0.73 and 0.82, respectively. This was the first study to develop prediction models for clinical remission associated with adalimumab treatment in UC patients by fecal analysis using FT-IR spectroscopy coupled with ML algorithms. Logistic regression, nonlinear support vector machines, and decision tree were suggested as the optimal prediction models for remission, and these were noninvasive, simple, inexpensive, and fast analyses that could be applied to personalized treatments.

Development and testing of the career decision-making self-efficacy scale for nursing students: a methodological study.

BACKGROUND: The conventional Career Decision-Making Self-Efficacy Scale does not reflect the situation in Korea due to different sociocultural attributes and fails to account for the unique nursing profession and changes in healthcare. We aimed to develop and psychometrically test the Career Decision-Making Self-Efficacy Scale for Nursing Students. METHODS: A methodological study using a newly developed questionnaire tool and investigation of the validity and reliability of the preliminary instrument. Data were collected from 400 nursing students through an online survey conducted in May 2021. We identified 56 preliminary items through a literature review and focus group interviews. Of them, 40 were completed with a content validity index > .80. Content, construct, and criterion-related validity; internal consistency reliability; and test-retest reliability were used in the analysis. RESULTS: Exploratory factor analysis revealed three factors including 21 items: adapting to work (20.5%), understanding the major (20.2%), and goal setting (16.4%), explaining 57.1% of the total variance. As a result of confirmatory factor analysis, 17 items in the three-factor structure were validated. Reliability, as verified by the test-retest interclass correlation coefficient, was .86 and Cronbach's α was .92. The final Career Decision-Making Self-Efficacy Scale for Nursing Students consists of 17 items: adapting to work (7 items); understanding the major (4 items); and goal setting (6 items). CONCLUSION: The scale developed to measure the career decision-making self-efficacy of nursing students showed sufficient validity and reliability.

Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1.

Fisetin is a kind of bioactive flavonol, widely present in various fruits such as strawberries and apples, and is known to act as a potent free radical scavenger. However, the mechanism of action related to the antioxidant activity of this compound in human retinal pigment epithelial (RPE) cells is not precisely known. In this study, we aimed to investigate whether fisetin could attenuate oxidative stress-induced cytotoxicity on human RPE ARPE-19 cells. To mimic oxidative stress, ARPE-19 cells were treated with hydrogen peroxide (H2O2), and fisetin significantly inhibited H2O2-induced loss of cell viability and increase of intracellular reactive oxygen species (ROS) production. Fisetin also markedly attenuated DNA damage and apoptosis in H2O2-treated ARPE-19 cells. Moreover, mitochondrial dysfunction in H2O2-treated cells was alleviated in the presence of fisetin as indicated by preservation of mitochondrial membrane potential, increase of Bcl-2/Bax expression ratio, and suppression of cytochrome c release into the cytoplasm. In addition, fisetin enhanced phosphorylation and nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2), which was associated with increased expression and activity of heme oxygenase-1 (HO-1). However, the HO-1 inhibitor, zinc protoporphyrin, significantly reversed the protective effect of fisetin against H2O2-mediated ARPE-19 cell injury. Therefore, our results suggest that Nrf2-mediated activation of antioxidant enzyme HO-1 may play an important role in the ROS scavenging activity of fisetin in RPE cells, contributing to the amelioration of oxidative stress-induced ocular disorders.

Förster Resonance Energy Transfer-Based Single-Cell Imaging Reveals Piezo1-Induced Ca2+ Flux Mediates Membrane Ruffling and Cell Survival.

A mechanosensitive ion channel, Piezo1 induces non-selective cation flux in response to various mechanical stresses. However, the biological interpretation and underlying mechanisms of cells resulting from Piezo1 activation remain elusive. This study elucidates Piezo1-mediated Ca2+ influx driven by channel activation and cellular behavior using novel Förster Resonance Energy Transfer (FRET)-based biosensors and single-cell imaging analysis. Results reveal that extracellular Ca2+ influx via Piezo1 requires intact caveolin, cholesterol, and cytoskeletal support. Increased cytoplasmic Ca2+ levels enhance PKA, ERK, Rac1, and ROCK activity, which have the potential to promote cancer cell survival and migration. Furthermore, we demonstrate that Piezo1-mediated Ca2+ influx upregulates membrane ruffling, a characteristic feature of cancer cell metastasis, using spatiotemporal image correlation spectroscopy. Thus, our findings provide new insights into the function of Piezo1, suggesting that Piezo1 plays a significant role in the behavior of cancer cells.

Factors Affecting Preventive Health Behaviors against COVID-19 in Nursing Students: A Cross-Sectional Study.

This study was conducted to identify factors affecting preventive health behaviors and to provide basic data for developing coronavirus disease 2019 (COVID-19) prevention and education programs. The participants were 218 students enrolled in two nursing colleges located near Gyeongsang and Jeolla province, Republic of Korea. Data were collected in December 2020 and analyses were conducted using t- and Scheffé tests, analysis of variance, Pearson correlation coefficients, and stepwise multiple regression with the SPSS/WIN 25.0 program (IBM Corp., Armonk, NY, USA). The factors affecting preventive health behaviors were fear of infection (ß = 0.26, p < 0.001), perceived benefits of COVID-19 infection control (ß = 0.20, p = 0.002), educational needs concerning COVID-19 infection control (ß = 0.18, p = 0.004), and perceived barriers to COVID-19 infection control (ß = 0.16, p = 0.011). To improve preventive health behaviors of nursing students against COVID-19, effective and practical education is required, and a systematic infection prevention education program should be developed considering the fear of COVID-19 infection and the perceived benefits and barriers in infection control.

Pathological Contribution of Extracellular Vesicles and Their MicroRNAs to Progression of Chronic Liver Disease.

Extracellular vesicles (EVs) are membrane-bound endogenous nanoparticles released by the majority of cells into the extracellular space. Because EVs carry various cargo (protein, lipid, and nucleic acids), they transfer bioinformation that reflects the state of donor cells to recipient cells both in healthy and pathologic conditions, such as liver disease. Chronic liver disease (CLD) affects numerous people worldwide and has a high mortality rate. EVs released from damaged hepatic cells are involved in CLD progression by impacting intercellular communication between EV-producing and EV-receiving cells, thereby inducing a disease-favorable microenvironment. In patients with CLD, as well as in the animal models of CLD, the levels of released EVs are elevated. Furthermore, these EVs contain high levels of factors that accelerate disease progression. Therefore, it is important to understand the diverse roles of EVs and their cargoes to treat CLD. Herein, we briefly explain the biogenesis and types of EVs and summarize current findings presenting the role of EVs in the pathogenesis of CLD. As the role of microRNAs (miRNAs) within EVs in liver disease is well documented, the effects of miRNAs detected in EVs on CLD are reviewed. In addition, we discuss the therapeutic potential of EVs to treat CLD.

Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is an important health concern worldwide and progresses into nonalcoholic steatohepatitis (NASH). Although prevalence and severity of NAFLD/NASH are higher in men than premenopausal women, it remains unclear how sex affects NAFLD/NASH pathophysiology. Formyl peptide receptor 2 (FPR2) modulates inflammatory responses in several organs; however, its role in the liver is unknown. Here we show that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH. NASH-like liver injury was induced in both sexes during choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) feeding, but compared with females, male mice had more severe hepatic damage. Fpr2 was more highly expressed in hepatocytes and healthy livers from females than males, and FPR2 deletion exacerbated liver damage in CDAHFD-fed female mice. Estradiol induced Fpr2 expression, which protected hepatocytes and the liver from damage. In conclusion, our results demonstrate that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH, suggesting a novel therapeutic target for NAFLD/NASH.

Career education needs of Korean nursing students and professionals: A cross-sectional survey.

BACKGROUND: The career education needs of nursing students and professionals can be met by analyzing the differences between the importance and need levels of their various career education needs, determining priorities, and developing a career education program reflecting these. This approach will enable learner-centered customized career education. OBJECTIVES: To investigate the differences in career education needs between nursing students and professionals, determine their respective priorities, and assess changes in needs between the two survey periods. DESIGN: Descriptive survey study. PARTICIPANTS: The first survey (2017) included 206 nursing students and 40 nursing professionals, while the second survey (2020) included 219 nursing students and 100 nursing professionals. METHODS: Data for the two surveys were collected through face-to-face, postal, and online questionnaire surveys. The research tool to measure career education needs was developed based on an existing tool, top queries on a website for nursing students' career education, literature review, expert opinions, and in-depth interviews with nursing students. RESULTS: The 10 top-ranked items in Jo and Lee's model reflecting the career education needs of nursing students and professionals were as follows: workplace and social etiquette, changes in the healthcare environment and global issues, setting up my career roadmap, interpersonal and communication skills, nursing professionalism and nursing ethics, understanding the latest healthcare policies, my personality type and values, roles and duties of clinical nurses, my aptitude and interest, and nurses' healthcare. Comparing the career education needs of nursing students and professionals between the two survey periods revealed higher scores in the education category of "understanding career" in the second survey. CONCLUSION: Nursing students' career awareness and development will be positively affected by a customized career education program based on the priority items derived from this study; such a program will help them attain nursing professionalism and enhance their occupational identity and job satisfaction.

Current Therapeutic Options and Potential of Mesenchymal Stem Cell Therapy for Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The therapeutic efficiency of current therapies for ALD is limited, and there is no FDA-approved therapy for ALD at present. Various strategies targeting pathogenic events in the progression of ALD are being investigated in preclinical and clinical trials. Recently, mesenchymal stem cells (MSCs) have emerged as a promising candidate for ALD treatment and have been tested in several clinical trials. MSC-released factors have captured attention, as they have the same therapeutic function as MSCs. Herein, we focus on current therapeutic options, recently proposed strategies, and their limitations in ALD treatment. Also, we review the therapeutic effects of MSCs and those of MSC-related secretory factors on ALD. Although accumulating evidence suggests the therapeutic potential of MSCs and related factors in ALD, the mechanisms underlying their actions in ALD have not been well studied. Further investigations of the detailed mechanisms underlying the therapeutic role of MSCs in ALD are required to expand MSC therapies to clinical applications. This review provides information on current or possible treatments for ALD and contributes to our understanding of the development of effective and safe treatments for ALD.

Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis.

Liver fibrosis is a common feature of chronic liver disease. Activated hepatic stellate cells (HSCs) are the main drivers of extracellular matrix accumulation in liver fibrosis. Hence, a strategy for regulating HSC activation is crucial in treating liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from various post-natal organs. Therapeutic approaches involving MSCs have been studied extensively in various diseases, including liver disease. MSCs modulate hepatic inflammation and fibrosis and/or differentiate into hepatocytes by interacting directly with immune cells, HSCs, and hepatocytes and secreting modulators, thereby contributing to reduced liver fibrosis. Cell-free therapy including MSC-released secretomes and extracellular vesicles has elicited extensive attention because they could overcome MSC transplantation limitations. Herein, we provide basic information on hepatic fibrogenesis and the therapeutic potential of MSCs. We also review findings presenting the effects of MSC itself and MSC-based cell-free treatments in liver fibrosis, focusing on HSC activation. Growing evidence supports the anti-fibrotic function of either MSC itself or MSC modulators, although the mechanism underpinning their effects on liver fibrosis has not been established. Further studies are required to investigate the detailed mechanism explaining their functions to expand MSC therapies using the cell itself and cell-free treatments for liver fibrosis.

Pathophysiological Aspects of Alcohol Metabolism in the Liver.

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.