The joint protective function of live- and dead-Lactobacillus plantarum GKD7 on anterior cruciate ligament transection induces osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory disease accompanied by joint pain, bone degradation, and synovial inflammation. Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß play key roles in chronic inflammation, and matrix metalloproteinase (MMP)3 is the first enzyme released by chondrocytes and synovial cells that promotes MMPs' degrading cartilage matrix (including collage II and aggrecan) function. Using an anterior cruciate ligament transection (ACLT) rat model, Lactobacillus plantarum GKD7 has shown anti-inflammatory and analgesic properties. The present investigation examined the chondroprotective effects of several dosages and formulas of GKD7 on rats in an ACLT-induced OA model. The findings indicate that oral treatment with both live-GKD7 (GKD7-L) and dead-GKD7 (GKD7-D), along with celecoxib (positive control), all reduce post-ACLT pain and inflammation in OA joints. Subsequently, the immunohistochemical staining results demonstrate that following GKD7-L and GKD7-D treatment, there was a reversal of the degradation of collagen II and aggrecan, as well as a decrease in the expression of IL-1ß and TNF-α on the synovial tissue and MMP3 on the cartilage. Accordingly, our findings imply that the treatment of both GKD7-L and GKD7-D has chondroprotective and analgesic effects on the OA rat model, and that celecoxib and GKD7-L at dosages (100 mg/kg) have comparable therapeutic benefits. As a result, we propose that both GKD7-L and GKD7-D are helpful supplements for OA management.

Perinatal lethal form Gaucher disease with compound heterozygosity of single nucleotide variants and copy number variations presenting as nonimmune hydrops fetalis and cerebellar hypoplasia: A case report.

OBJECTIVE: To present the ultrasound imaging and genetic diagnosis of a fetus with prenatal lethal form of Gaucher disease. CASE REPORT: A 37-year-old primiparous woman was pregnant at her 23 weeks of gestation and the prenatal fetal ultrasound revealed hydrops fetalis, cerebellum hypoplasia, and fetal immobility. The pregnancy was terminated due to major fetal anomaly, and whole exome sequencing (WES) analysis of fetal tissue and parental blood unveiled a pathogenic variant in exon 10 of the GBA gene (NM_001005741.3: c.1265T > G: p.L422R) originating from the mother. Additionally, a novel CNV (chr1: 155204785-155205635 deletion, 0.85 kb) spanning exon 10-12 in the GBA gene was identified from the father. This compound heterozygosity confirmed the diagnosis of prenatal lethal form of Gaucher disease and was informative for genetic counseling. CONCLUSION: WES is a powerful tool to detect pathogenic variants among fetuses with nonimmune hydrops fetalis and complex abnormality from prenatal ultrasound. Compound heterozygosity consisted of single nucleotide variants (SNV) and copy number variations (CNVs) may lead rare inherited metabolic disorders including prenatal lethal form of Gaucher disease.

The Novel Application of EUK-134 in Retinal Degeneration: Preventing Mitochondrial Oxidative Stress-Triggered Retinal Pigment Epithelial Cell Apoptosis by Suppressing MAPK/p53 Signaling Pathway.

Age-related macular degeneration (AMD), a leading cause of blindness, is characterized by mitochondrial dysfunction of retinal pigment epithelium (RPE) cells. EUK-134 is a mimetic of SOD2 and catalase, widely used for its antioxidant properties in models of light-induced damage or oxidative stress. However, its effects on the retina are not yet clear. Here, we investigated the capability of EUK-134 in averting AMD using sodium iodate (NaIO3)-induced Balb/c mouse and ARPE-19 cells (adult RPE cell line). In vivo, EUK-134 effectively antagonized NaIO3-induced retinal deformation and prevented outer and inner nuclear layer thinning. In addition, it was found that the EUK-134-treated group significantly down-regulated the expression of cleaved caspase-3 compared with the group treated with NaIO3 alone. Our results found that EUK-134 notably improved cell viability by preventing mitochondrial ROS accumulation-induced membrane potential depolarization-mediated apoptosis in NaIO3-inducted ARPE-19 cells. Furthermore, we found that EUK-134 could inhibit p-ERK, p-p38, p-JNK, p-p53, Bax, cleaved caspase-9, cleaved caspase-3, and cleaved PARP by increasing Bcl-2 protein expression. Additionally, we employed MAPK pathway inhibitors by SB203580 (a p38 inhibitor), U0126 (an ERK inhibitor), and SP600125 (a JNK inhibitor) to corroborate the aforementioned observation. The results support that EUK-134 may effectively prevent mitochondrial oxidative stress-mediated retinal apoptosis in NaIO3-induced retinopathy.

Caffeic acid derivative MPMCA suppresses osteoclastogenesis and facilitates osteoclast apoptosis: implications for the treatment of bone loss disorders.

Osteoclast activity plays a crucial role in the pathological mechanisms of osteoporosis and bone remodeling. The treatment of these disorders involves the use of pharmacological medicines that work by inhibiting the activity of osteoclasts. Nevertheless, the prevalent and infrequent negative consequences of current antiresorptive and bone anabolic treatments pose significant drawbacks, hence restricting their prolonged administration in patients, particularly those who are elderly and/or suffer from many medical conditions. We are currently in the process of creating a new molecule called N-(4-methoxyphen) methyl caffeamide (MPMCA), which is a derivative of caffeic acid. This compound has shown potential in preventing the production of osteoclasts and causing existing osteoclasts to undergo cell apoptosis. Our investigation discovered that MPMCA hinders osteoclast function via suppressing the MAPK pathways. The expectation is that the findings of this study will stimulate the advancement of a novel approach to treating anti-resorption.

Genomic instabilities in hepatocellular carcinoma: biomarkers and application in immunotherapies.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a "genomically unstable" cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients' well-being.

A cross-sectional study of perception toward university social responsibility and environmental sustainability practices in medical university students under promotion of sustainable thinking within the university.

This study aims to assess the associations among students' perceptions of climate change, university social responsibility (USR), and environmental sustainability practices at a medical university. It also aims to identify the factors associated with these elements. A cross-sectional self-report study was conducted with a total sample of 416 undergraduate students from a medical university in Taiwan during October 2019. Data gathered comprised sociodemographic characteristics, perceptions of climate change issues, environmental sustainability practices, measure for perception toward USR, and transportation modes. Chi-square test, Fisher's exact test, two-sample t test, and multiple linear regression models were used. Results of multiple linear regression demonstrated that the level of certainty in climate change existence (extremely and mostly certain vs somewhat or not certain at all, 1.45 [0.68]), score for usage of nonpublic transportation (per 1-point increase, 0.52 [0.25]), and students' perception toward USR (per 1-point increase, 0.14 [0.04]) were associated with the total score of environmental sustainability practice (R-square = 11.47%). In addition, school year (non-freshmen vs freshmen, -1.64 [0.65]) and environmental sustainability practices (per 1-point increase, 0.23 [0.06]) were associated with the total score of students' perception of USR (R-square = 6.57%). Promoting environmental sustainability among university students can be achieved by implementing USR-oriented courses or activities. Our research is pioneering in investigating and discussing the perceived USR and environmental sustainability practices among university students in Taiwan.

Bouncing of Leidenfrost steel balls on water surface.

A steel ball with a density higher than that of water can bounce on a water surface when heated to a temperature well above the Leidenfrost point. In this letter, an experiment is conducted where heated steel balls are released onto a water surface. The heated steel ball descends into the liquid, thus causing the liquid to evaporate and form a vapor cushion with an upward force that lifts the steel ball. Subsequently, the steel ball bounces off the water surface, like a solid ball bouncing off an elastic surface without sinking into the water. This phenomenon is known as the inverse Leidenfrost effect. In this letter, we evaluate the various motion behaviors of spheres at different Reynolds numbers and temperatures. Additionally, we analyze the bouncing behavior of solid spheres on a free liquid surface and examine the various force components.

Live and Dead Clostridium butyricum GKB7 Diminish Osteoarthritis Pain and Progression in Preclinical Animal Model.

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti-inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7-L and GKB7-D) in a preclinical anterior cruciate ligament transection (ACLT)-enhanced OA procedure. Oral administration of GKB7-L and GKB7-D ameliorated ACLT-induced bone pain as assessed by weight-bearing behavioral testing but did not affect body weight. Micro-computed tomography (CT) results showed that GKB7-L and GKB7-D diminished ACLT-induced bone destruction and loss. GKB7-L and GKB7-D-enriched therapies also reduced ACLT-induced production of the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, as well as the chondrolytic factor matrix metalloproteinase (MMP)-3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7-L or GKB7-D can be beneficial in the prevention and treatment of OA.

Repulsion, Acceleration, and Coalescence between Water Droplets on Superhydrophobic Glass by Triboelectrification.

Manipulating the motion of water droplets on surfaces, which is crucial for various applications, such as microfluidics and heat transfer, presents considerable challenges, primarily due to the significant influence of capillary forces. This effect becomes more pronounced when droplets are in close proximity, often resulting in undesired coalescence. Triboelectrification, which involves charging pure water droplets, is a promising approach to enhance the ability to manipulate water droplets. For effective triboelectrification, charges must accumulate within the droplets; this ensures efficient and sustained droplet manipulation while minimizing dissipation. Low-friction, superhydrophobic, insulating surfaces are ideal for this purpose. However, few studies have explored the application of insulating superhydrophobic surfaces to manipulate droplet motion. In this study, we investigated the behavior of water droplets on insulating superhydrophobic quartz surfaces after triboelectrification. The droplets acquired significant charge when dripped onto a superhydrophobic glass surface. Consequently, these charged droplets exhibited behaviors such as repulsion and acceleration from one another, uphill movement, and rapid long-distance transport to specific positions. These advancements in droplet manipulation techniques hold promise for diverse fields such as microfluidics and heat exchangers.

Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway.

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Quantifying source contributions to ambient NH3 using Geo-AI with time lag and parcel tracking functions.

Ambient ammonia (NH3) plays an important compound in forming particulate matters (PMs), and therefore, it is crucial to comprehend NH3's properties in order to better reduce PMs. However, it is not easy to achieve this goal due to the limited range/real-time NH3 data monitored by the air quality stations. While there were other studies to predict NH3 and its source apportionment, this manuscript provides a novel method (i.e., GEO-AI)) to look into NH3 predictions and their contribution sources. This study represents a pioneering effort in the application of a novel geospatial-artificial intelligence (Geo-AI) base model with parcel tracking functions. This innovative approach seamlessly integrates various machine learning algorithms and geographic predictor variables to estimate NH3 concentrations, marking the first instance of such a comprehensive methodology. The Shapley additive explanation (SHAP) was used to further analyze source contribution of NH3 with domain knowledge. From 2016 to 2018, Taichung's hourly average NH3 values were predicted with total variance up to 96%. SHAP values revealed that waterbody, traffic and agriculture emissions were the most significant factors to affect NH3 concentrations in Taichung among all the characteristics. Our methodology is a vital first step for shaping future policies and regulations and is adaptable to regions with limited monitoring sites.

The associations among peptic ulcer disease, Helicobacter pylori infection, and abdominal aortic aneurysms: A nationwide population-based cohort study.

BACKGROUND: There are overlapping risk factors and underlying molecular mechanisms for both peptic ulcer disease (PUD) and abdominal aortic aneurysm (AAA). Despite improvements in the early diagnosis and treatment of AAA, ruptured AAAs continue to cause a substantial number of deaths. Helicobacter pylori are Gram-negative, microaerophilic bacteria that are now recognized as the main cause of PUD. H. pylori infection (HPI) is associated with an increased risk of certain cardiovascular diseases. HPIs can be treated with at least two different antibiotics to prevent bacteria from developing resistance to one particular antibiotic. METHODS: We conducted a population-based cohort study using the National Health Insurance Research Database to evaluate whether associations exist among PUD, HPI, and eradication therapy for HPI and AAA. The primary outcome of this study was the cumulative incidence of AAA among patients with or without PUD and HPI during the 14-year follow-up period. RESULTS: Our analysis included 7003 patients with PUD/HPI, 7003 patients with only PUD, and another 7003 age-, sex-, and comorbidity-matched controls from the database. We found that patients with PUD/HPI had a significantly increased risk of AAA compared to those with PUD alone and matched controls. The patients who had PUD/HPI had a significantly higher cumulative risk of developing AAA than those with PUD and the comparison group (2.67 % vs. 1.41 % vs. 0.73 %, respectively, p < 0.001). Among those patients with PUD/HPI, patients who had eradication therapy had a lower incidence of AAA than those without eradication therapy (2.46 % vs. 3.88 %, p = 0.012). CONCLUSIONS: We revealed an association among PUD, HPI, and AAA, even after adjusting for age, sex, comorbidities, and annual medical follow-up visits. Notably, we found that HPI eradication therapy reduced the incidence of AAA among patients with PUD.

Indigofera suffruticosa aerial parts extract induce G2/M arrest and ATR/CHK1 pathway in Jurkat cells.

BACKGROUND: Indigofera suffruticosa Mill. is used as a folk medicine for treating patients with leukemia, however very little is known regarding the molecular mechanism of its anti-leukemic activity and the chemical profile of the active extract. The present study aimed to reveal the molecular effect of I. suffruticosa aerial parts extract (ISAE) on leukemia cells and its chemical constituents. METHODS: Cytotoxicity of ISAE were determined by resazurin viability assay, multitox - Glo multiplex cytotoxicity assay, and Annexin V staining assay. Cell cycle profiles were revealed by propidium iodide staining assay. The effects of ISAE on G2/M arrest signaling and DNA damage were evaluated by Western blot assay and phospho-H2A.X staining assay. The chemical profile of ISAE were determined by tandem mass spectroscopy and molecular networking approach. RESULTS: We showed that the acute lymphoblastic leukemia cell line Jurkat cell was more responsive to ISAE treatment than other leukemia cell lines. In contrast, ISAE did not induce cytotoxic effects in normal fibroblast cells. Cell cycle analysis revealed that ISAE triggered G2/M arrest in Jurkat cells in dose- and time-dependent manners. Elevation of annexin V-stained cells and caspase 3/7 activity suggested ISAE-induced apoptosis. Furthermore, ISAE alone could increase the phosphorylation of CDK1 at Y15 and activate the ATR/CHK1/Wee1/CDC25C signaling pathway. However, the addition of caffeine, a widely used ATR inhibitor to ISAE, reduced the phosphorylation of ATR, CHK1, and CDK1, as well as G2/M arrest in Jurkat cells. Moreover, increased phospho-H2A.X stained cells indicated the involvement of DNA damage in the anti-leukemic effect of ISAE. Finally, qualitative analysis using UPLC-tandem mass spectroscopy and molecular networking revealed that tryptanthrin was the most abundant organoheterocyclic metabolite in ISAE. At equivalent concentrations to ISAE, tryptanthrin induced G2/M arrest of Jurkat cells, which can be prevented by caffeine. CONCLUSIONS: ISAE causes G2/M arrest via activating ATR/CHK1/CDK1 pathway and tryptanthrin is one of the active components of ISAE. Our findings provide subtle support to the traditional use of I. suffruitcosa in leukemia management in folk medicine.

A machine learning-based ensemble model for estimating diurnal variations of nitrogen oxide concentrations in Taiwan.

Air pollution is inextricable from human activity patterns. This is especially true for nitrogen oxide (NOx), a pollutant that exists naturally and also as a result of anthropogenic factors. Assessing exposure by considering diurnal variation is a challenge that has not been widely studied. Incorporating 27 years of data, we attempted to estimate diurnal variations in NOx across Taiwan. We developed a machine learning-based ensemble model that integrated hybrid kriging-LUR, machine-learning, and an ensemble learning approach. Hybrid kriging-LUR was performed to select the most influential predictors, and machine-learning algorithms were applied to improve model performance. The three best machine-learning algorithms were suited and reassessed to develop ensemble learning that was designed to improve model performance. Our ensemble model resulted in estimates of daytime, nighttime, and daily NOx with high explanatory powers (Adj-R2) of 0.93, 0.98, and 0.94, respectively. These explanatory powers increased from the initial model that used only hybrid kriging-LUR. Additionally, the results depicted the temporal variation of NOx, with concentrations higher during the daytime than the nighttime. Regarding spatial variation, the highest NOx concentrations were identified in northern and western Taiwan. Model evaluations confirmed the reliability of the models. This study could serve as a reference for regional planning supporting emission control for environmental and human health.

Estimating morning and evening commute period O3 concentration in Taiwan using a fine spatial-temporal resolution ensemble mixed spatial model with Geo-AI technology.

Elevated levels of ground-level ozone (O3) can have harmful effects on health. While previous studies have focused mainly on daily averages and daytime patterns, it's crucial to consider the effects of air pollution during daily commutes, as this can significantly contribute to overall exposure. This study is also the first to employ an ensemble mixed spatial model (EMSM) that integrates multiple machine learning algorithms and predictor variables selected using Shapley Additive exExplanations (SHAP) values to predict spatial-temporal fluctuations in O3 concentrations across the entire island of Taiwan. We utilized geospatial-artificial intelligence (Geo-AI), incorporating kriging, land use regression (LUR), machine learning (random forest (RF), categorical boosting (CatBoost), gradient boosting (GBM), extreme gradient boosting (XGBoost), and light gradient boosting (LightGBM)), and ensemble learning techniques to develop ensemble mixed spatial models (EMSMs) for morning and evening commute periods. The EMSMs were used to estimate long-term spatiotemporal variations of O3 levels, accounting for in-situ measurements, meteorological factors, geospatial predictors, and social and seasonal influences over a 26-year period. Compared to conventional LUR-based approaches, the EMSMs improved performance by 58% for both commute periods, with high explanatory power and an adjusted R2 of 0.91. Internal and external validation procedures and verification of O3 concentrations at the upper percentile ranges (in 1%, 5%, 10%, 15%, 20%, and 25%) and other conditions (including rain, no rain, weekday, weekend, festival, and no festival) have demonstrated that the models are stable and free from overfitting issues. Estimation maps were generated to examine changes in O3 levels before and during the implementation of COVID-19 restrictions. These findings provide accurate variations of O3 levels in commute period with high spatiotemporal resolution of daily and 50m * 50m grid, which can support control pollution efforts and aid in epidemiological studies.

Evaluating long-term and high spatiotemporal resolution of wet-bulb globe temperature through land-use based machine learning model.

BACKGROUND: The increase in global temperature and urban warming has led to the exacerbation of heatwaves, which negatively affect human health and cause long-term loss of work productivity. Therefore, a global assessment in temperature variation is essential. OBJECTIVE: This paper is the first of its kind to propose land-use based spatial machine learning (LBSM) models for predicting highly spatial-temporal variations of wet-bulb globe temperature (WBGT), which is a heat stress indicator used to assess thermal comfort in indoor and outdoor environments, specifically for the main island of Taiwan. METHODS: To develop spatiotemporal prediction models for both the working period and noon period, we calculated the WBGT of each weather station from 2001 to 2019 using temperature, humidity, and solar radiation data. These WBGT estimations were then used as the dependent variable for developing the spatiotemporal prediction models. To enhance model performance, we used innovative approaches that combined SHapley Additive exPlanations (SHAP) values for the selection of non-linear variables, along with machine learning algorithms for model development. RESULTS: When incorporating temperature along with other land-use/land cover predictor variables, the performance of LBSM models was excellent, with an R2 value of up to 0.99. The LBSM models explained 98% and 99% of the spatial-temporal variations in WBGT for the working and noon periods, respectively, within the complete models. In the temperature-excluded models, the explained variances were 94% and 96% for the working and noon periods, respectively. IMPACT: WBGT is a common method used by many organizations to access the impact of heat stress on human beings. However, limited studies have mentioned the association between WBGT and health impacts due to the absence of spatiotemporal databases. This study develops a new approach using land-use-based spatial machine learning (LBSM) models to better predict the fine spatial-temporal WBGT levels, with a 50-m × 50-m grid resolution for both working time and noontime. Our proposed methodology could be used in future studies aimed at evaluating the potential long-term loss of work productivity due to the effects of global warming or urban heat island.

Patients with Hepatitis C Undergoing Direct-Acting Antiviral Treatment Have a Lower SARS-CoV-2 Infection Rate.

This study retrospectively analyzed the medical records of 602 patients with first-time positive results for the HCV nucleic acid test between 1 May 2021 and 31 March 2023, exploring the association between DAA treatment and SARS-CoV-2 infection. The results showed that 9.8% of HCV patients were co-infected with SARS-CoV-2. Gender, age, vaccination status, and HCV genotype did not significantly affect SARS-CoV-2 infection. However, patients undergoing DAA treatment showed significantly lower rates of SARS-CoV-2 infection and mortality compared to those not undergoing DAA treatment. The analysis also compared patients undergoing different DAA treatments, with Epclusa and Maviret showing superior protection against SARS-CoV-2. Furthermore, this study explored the severity and mortality of SARS-CoV-2 infection in patients undergoing and having completed DAA treatment. It revealed that patients diagnosed with COVID-19 during DAA treatment experienced only mild symptoms, and none died, suggesting a potential protective effect of DAA treatment against severe outcomes of SARS-CoV-2 infection. The findings contribute to the understanding of the interplay between HCV, DAA treatment, and SARS-CoV-2 infection, highlighting the need for continued monitoring and healthcare measures for individuals with chronic conditions during the ongoing COVID-19 pandemic.

High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression.

High mobility group box-1 (HMGB1) is a driver of inflammation in various muscular diseases. In a previous study, we determined that HMGB1 induced the atrophy of skeletal muscle by impairing myogenesis. Skeletal muscle regeneration after injury is dependent on pair box 7 (Pax-7)-mediated myogenic differentiation. In the current study, we determined that the HMGB1-induced downregulation of Pax-7 expression in myoblasts inhibited the regeneration of skeletal muscle. We also determined that HMGB1 inhibits Pax-7 and muscle differentiation by increasing miR-342-5p synthesis via receptors for advanced glycation end-products (RAGE), toll-like receptor (TLR) 2, TLR4, and c-Src signaling pathways. In a mouse model involving glycerol-induced muscle injury, the therapeutic inhibition of HMGB1 was shown to rescue Pax-7 expression and muscle regeneration. The HMGB1/Pax-7 axis is a promising therapeutic target to promote muscular regeneration.