Trajectories of activities of daily living according to dementia among middle-aged and older people in South Korea: a longitudinal study from 2006 to 2020 (14 years).

Introduction: The aging population in South Korea faces numerous health challenges, one of which is the decline in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). This study aims to investigate the patterns of change in ADL and IADL among older adults and examines how these patterns vary between individuals with and without dementia. Methods: We conducted an analysis of data collected from the Korea Longitudinal Study of Ageing (KLoSA) between 2006 and 2022. Our cohort consisted of individuals aged 45 and older with non-dementia conditions, including mild cognitive impairment (N=6042), and a smaller group with dementia (N=91). Using Latent Growth Curve Models, we explored the developmental trajectories of ADL and IADL among our sample. Results: Our findings indicate a linear decline in both ADL and IADL scores as individuals age. The decline in IADL was more pronounced in the dementia group, suggesting a greater sensitivity to sociocultural factors within this domain. The data revealed that individuals with dementia had consistently lower ADL and IADL scores. Notably, the variance in scores within the dementia group increased with age, signifying a worsening in daily living performance and an increase in individual variation (F=226.630, p<.001). Discussion: The results of this study underscore the impact of dementia on both the self-regulation function and the social and cultural aspects of daily living performance, particularly reflected in IADL scores. These findings point to the necessity for comprehensive care strategies that address the multifaceted needs of older adults with dementia, including support for complex daily activities that are influenced by sociocultural factors.

Epidemiology and Healthcare Utilization in Pediatric Multiple Sclerosis and Neuromyelitis Optica: A Nationwide Population-Based Study in South Korea (2016-2020).

Pediatric multiple sclerosis (MS) and neuromyelitis optica (NMO) are rare acquired demyelinating syndrome with limited epidemiological data available, particularly in non-Western setting. This study aimed to demonstrate the epidemiology of pediatric MS and NMO in South Korea and to analyze of healthcare utilization and economic burden associated with these conditions. Using a nationwide population-based database from the Korean Health Insurance Review and Assessment Service database, we identified pediatric cases (age < 20 years) of MS and NMO from 2016 to 2020. We analyzed incidence, prevalence, healthcare utilization and medical costs. The study found low age-standardized incidence and prevalence rates for pediatric MS and NMO in South Korea. There was a marked disparity in healthcare utilization between urban and rural areas. Most healthcare interactions occurred in tertiary hospitals in urban settings, particularly in Seoul. The study also highlighted the substantial economic burden associated with the management of rare diseases, with annual variability in medical costs. Pediatric MS and NMO are extremely rare in South Korea, with significant regional disparity in healthcare utilization. The findings emphasize the need for targeted healthcare policies to improve access and reduce disparities, particularly for chronic and rare diseases requiring specialized care.

MicroRNA 429 regulates MMPs expression by modulating TIMP2 expression in colon cancer cells and inflammatory colitis.

BACKGROUND: In a previous study, we found that the expression of microRNA 429 (MIR429) was decreased in dextran sodium sulfate (DSS)-induced mouse colitis tissues. OBJECTIVE: In this study, we aimed to investigate the interaction of MIR429 with TIMP metallopeptidase inhibitor 2 (TIMP2), one of its candidate target genes, in human colorectal cancer (CRC) cells and DSS-induced mouse colitis tissues. METHODS: A luciferase reporter system was used to confirm the effect of MIR429 on TIMP2 expression. The expression levels of MIR429 and target genes in cells or tissues were evaluated through quantitative RT-PCR, western blotting, or immunohistochemistry. RESULTS: We found that the expression level of MIR429 was downregulated in human CRC tissues, and also showed that TIMP2 is a direct target gene of MIR429 in CRC cell lines. Furthermore, MIR429 regulate TIMP2-mediated matrix metallopeptidases (MMPs) expression in CRC cells. We also generated cell lines stably expressing MIR429 in CRC cell lines and showed that MIR429 regulates the expression of MMPs by mediating TIMP2 expression. In addition to human CRC tissues, we found that TIMP2 was highly expressed in mouse colitis tissues and human ulcerative colitis (UC) tissues. CONCLUSIONS: Our findings suggest that the expression of endogenous MIR429 was reduced in human CRC tissues and colitis, leading to upregulation of its target gene TIMP2. The upregulation of TIMP2 by decreased MIR429 expression in CRC tissues and inflamed tissues suggests that it may affect extracellular matrix (ECM) remodeling through downregulation of MMPs. Therefore, MIR429 may have therapeutic value for human CRC and colitis.

Effects of Korean Versus Western Diets on Reproductive Function in Young Korean Men: A 12-Week Randomized Parallel Clinical Trial.

Background: Studies report that diet may have contributed to a 50-60% decrease in human sperm quality over the past few decades. Unhealthy lifestyles affect the structure of spermatozoa, affecting the male reproductive potential. This study aimed to compare the effects of Korean and Western diets on reproductive function in young male Koreans. Methods: Study participants were provided either the Korean Diet (KD group) or the Western Diet (WD group) for 12 weeks. Semen quality parameters such as volume, motility, cell count, and sex hormone levels were evaluated. Sexual function was assessed using the International Index of Erectile Function and the Male Sexual Health Questionnaire. Efficacy and safety evaluations were conducted at baseline, 8 weeks, and 12 weeks. Results: The KD group demonstrated a significantly increased sperm motility after 8 weeks relative to baseline but decreased after 12 weeks. In contrast, sperm motility in the WD group significantly decreased after 8 weeks compared with baseline and remained constant after 12 weeks. Statistically, a near-significant difference was observed between groups (p = 0.057). Similarly, free testosterone levels in the KD group increased after 12 weeks compared with baseline, whereas that in the WD group decreased. The free testosterone levels in the KD group were significantly higher than those in the WD group (p = 0.020). There were no statistically significant differences in other sex hormone and sexual function questionnaires between the groups. None of the participants reported any severe side effects, and no significant alterations in clinical diagnostic test values were detected. Conclusion: The results of the study strongly reveal that KD positively affects sperm motility and male hormone levels in young men, indicating potential benefits for reproductive function.

Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model.

Epithelial cell adhesion molecules (EpCAMs) have been identified as surface markers of proliferating ductal cells, which are referred to as liver progenitor cells (LPCs), during liver regeneration and correspond to malignancies. These cells can differentiate into hepatocytes and biliary epithelial cells (BECs) in vitro. EpCAM-positive LPCs are involved in liver regeneration following severe liver injury; however, the in vivo function of EpCAMs in the regenerating liver remains unclear. In the present study, we used a zebrafish model of LPC-driven liver regeneration to elucidate the function of EpCAMs in the regenerating liver in vivo. Proliferating ductal cells were observed after severe hepatocyte loss in the zebrafish model. Analyses of the liver size as well as hepatocyte and BEC markers revealed successful conversion of LPCs to hepatocytes and BECs in epcam mutants. Notably, epcam mutants exhibited severe defects in intrahepatic duct maturation and bile acid secretion in regenerating hepatocytes, suggesting that epcam plays a critical role in intrahepatic duct reconstruction during LPC-driven liver regeneration. Our findings provide insights into human diseases involving non-parenchymal cells, such as primary biliary cholangitis, by highlighting the regulatory effect of epcam on intrahepatic duct reconstruction.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

The Effectiveness and Safety of Cupping Therapy on CV8 Shenque for Urticaria; a Protocol for Systematic Review and Meta-Analysis.

Purpose: Urticaria is a common mast-cell-driven disease that poses a great burden on patients and society. Suggested therapeutic methods include avoidance of triggers and the use of medications, such as H1-antihistamines; however, limitations remain regarding efficacy, dealing with comorbidities, and adverse events. Cupping therapy (CT) at CV8 Shenque has been used in traditional Chinese medicine for the treatment of various dermatological diseases, including urticaria. The efficacy of the treatment has been revealed by previous clinical trials and case reports. This study was performed to provide a protocol for a systematic review and meta-analysis to analyze the effectiveness and safety of CT at CV8 Shenque for urticaria patients. Patients and Methods: Searches of electronic databases using manual searches and contact with the corresponding authors will be performed using predefined criteria for all randomized controlled trials on CT at CV8 Shenque for urticaria patients. Every part of the process will be conducted by two independent researchers, with conflicts being solved by a third author. The primary outcomes will be symptom scores, quality of life, and effective rate. Secondary outcomes will be adverse events and diagnostic test results. RevMan 5.4 software will be used to perform the meta-analysis. The Cochrane Collaboration "Risk of bias" tool will be used for risk of bias judgments. Results: Our study will evaluate the effectiveness and safety of CT at CV8 Shenque as a treatment option for urticaria. Conclusion: This systematic review is the first to investigate the effect of CT at CV8 Shenque for urticaria patients. Our study will provide objective evidence of an alternative approach to urticaria for clinicians and patients. Study Registration: PROSPERO (Registration number: CRD42023434913).

Effects of Unripe Black Raspberry Extract Supplementation on Male Climacteric Syndrome and Voiding Dysfunction: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

Male climacteric syndrome (MCS) is a medical condition that can affect middle-aged men whose testosterone levels begin to decline considerably. These symptoms may include fatigue, decreased libido, mood swings, and disturbed sleep. MCS can be managed with lifestyle modifications and testosterone replacement. However, testosterone therapy may cause number of side effects, including an increased risk of cardiovascular issues. This study aims to evaluate the efficacy and safety of unripe black raspberry extract (BRE) against MCS and voiding dysfunction in men with andropause symptoms. A total of 30 subjects were enrolled and randomly assigned to the BRE group (n = 15) or the placebo group (n = 15). Participants were supplemented with 4800 mg BRE or placebo twice daily for 12 weeks. The impact of BRE was assessed using the Aging Male's Symptoms (AMS scale), International Prostate Symptom Score (IPSS) and the IPSS quality of life index (IPSS-QoL). Additionally, male sex hormones, lipid profiles, and anthropometric indices were assessed 6 and 12 weeks after treatment. The AMS scores did not differ significantly between the two groups. In the BRE group, the total IPSS and IPSS-QoL scores decreased significantly after 12 weeks compared to baseline (p < 0.05), but there was no significant difference compared to the placebo group. However, a significant difference was observed in the IPSS voiding symptoms sub-score compared to the placebo group. Furthermore, LDL-C and TC levels were also significantly lower in the BRE group than in the placebo group (p < 0.05). Collectively, the study provides strong evidence supporting the safety of BRE as a functional food and its supplementation potentially enhances lipid metabolism and alleviates MCS and dysuria symptoms, limiting the development of BPH.

Incidence of Pediatric Acute Disseminated Encephalomyelitis During the Coronavirus Disease 2019 Pandemic in South Korea.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder of the central nervous system that is usually triggered by infections. We aimed to determine the temporal trends in the incidence of ADEM before and during the pandemic and their correlation with viral epidemiology. METHODS: We conducted a nationwide, population-based, retrospective, ADEM cohort study by using the Health Insurance Review and Assessment Service database. New-onset ADEM was defined as a patient (age <19 years) who was hospitalized with a diagnostic code of G04.0, G36.8, and G36.9 and a prescription of intravenous methylprednisolone. The National Infectious Disease Surveillance System was used to collect the nationwide viral epidemics. RESULTS: A total of 185 new-onset pediatric ADEM cases were included. The mean patient age was 7.0 ± 4.9 years. The incidence of ADEM was 0.34 to 0.48 of 100,000 persons per year before the pandemic, which dropped to 0.22 of 100,000 persons per year during the first pandemic year. The risk of ADEM occurrence was approximately 1.74% higher during the prepandemic years compared with the first pandemic year (odds ratio = 1.017, P = 0.009). There was a weak positive correlation between acute respiratory viral infection and ADEM incidence (r = 0.28, P = 0.03). CONCLUSION: This study demonstrates how infection control during the early coronavirus disease 2019 (COVID-19) pandemic influenced the incidence of ADEM. The low incidence of ADEM in the early COVID-19 pandemic may be related to the decline in acute respiratory viral infections, which are potential triggers of ADEM.

MicroRNA 452 regulates SHC1 expression in human colorectal cancer and colitis.

BACKGROUND: Human microRNA 452 (MIR452) has been linked to both colorectal cancer (CRC) tissues and dextran sulfate sodium (DSS)-induced colitis. OBJECTIVE: We analyzed the correlation between MIR452 and its putative target gene in human CRC cells and in mouse colitis tissues. METHODS: Luciferase reporter assay confirmed that Src homologous and collagen adaptor protein 1 (SHC1) is a direct target of MIR452. Furthermore, the expression of proteins or mRNA was assessed by immunohistochemical analysis, Western blot, or quantitative RT-PCR (qRT-PCR). RESULTS: We found that MIR452 has a potential binding site at 3'-UTR of SHC1. Likewise, MIR452 or siSHC1 transfection dramatically reduced the level of cellular SHC1 in CRC cells. The expression of SHC1 was frequently downregulated in both human CRC tissues and mouse colitis tissues. In CRC cells, we demonstrated that MIR452 regulated the expression of genes involved in the SHC1-mediated KRAS-MAPK signal transduction pathways. CONCLUSION: These findings suggest a potential defense mechanism in which MIR452 regulation of the adaptor protein SHC1 maintains cellular homeostasis during carcinogenesis or chronic inflammation. Therefore, MIR452 may have therapeutic value for human early-stage CRC and colitis.

MicroRNA 133A Regulates Cell Proliferation, Cell Migration, and Apoptosis in Colorectal Cancer by Suppressing CDH3 Expression.

MicroRNAs are endogenous, non-coding RNA that play an essential role in colorectal carcinoma (CRC) pathogenesis by targeting specific genes. This research aimed to determine and validate the target genes of the MIR133A associated with CRC. We verified that cadherin 3 (CDH3) is the direct target gene of MIR133A using a luciferase reporter assay, quantitative RT-PCR, and western blot analyses. CDH3 mRNA and protein expression were reduced significantly in CRC cells after transfection with MIR133A or siCDH3. We also verified that MIR133A regulated CDH3-mediated catenin, matrix metalloproteinase, apoptosis, and the epithelial-mesenchymal transition (EMT) pathway. Knockdown of CDH3 in CRC cell lines by siCDH3 produced similar results. Compared with adjacent non-tumor tissues, CDH3 protein expression was upregulated in CRC tissues, which is further confirmed by immunohistochemistry. Additionally, molecular and functional studies revealed that cell viability, migration, and colony formation were significantly reduced, and apoptosis was increased in CRC cell lines transfected with MIR133A or siCDH3. Our results suggest that MIR133A regulates CDH3 expression in human CRC.

Corrigendum: Incidence of Guillain-Barré syndrome in South Korea during the early COVID-19 pandemic.

[This corrects the article DOI: 10.3389/fneur.2023.1125455.].

Incidence of Guillain-Barré syndrome in South Korea during the early COVID-19 pandemic.

Objectives: Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, often triggered by infection. We aimed to investigate how the incidence of GBS changed in the early stages of the coronavirus 2019 (COVID-19) pandemic when nationwide infections declined due to non-pharmaceutical interventions. Methods: We conducted a nationwide population-based retrospective GBS cohort study using data from the Health Insurance Review and Assessment Service of Korea. Patients with new-onset GBS were defined as those who were first hospitalized between 1 January 2016 and 31 December 2020 with an International Classification of Disease, 10th Revision code, for GBS (G61.0) as a primary diagnosis. The incidence of GBS in the pre-pandemic years (2016-2019) was compared with that in the first pandemic year (2020). Nationwide epidemiological data for infections were collected from the national infectious disease surveillance system. A correlation analysis was performed to determine the incidence of GBS and nationwide trends of various infections. Results: Overall, 3,637 new-onset GBS cases were identified. The age-standardized incidence of GBS in the first pandemic year was 1.10 (95% confidence interval, 1.01-1.19) per 100,000 persons. Compared to the first pandemic year, the incidence of GBS during the pre-pandemic years (1.33-1.68/100,000 persons/year) was significantly higher, with incidence rate ratios of 1.21-1.53 (P < 0.001). Nationwide cases of upper respiratory viral infections were significantly reduced in the first pandemic year; however, Campylobacter infections peaked in the summer of the pandemic. The nationwide epidemiology of parainfluenza virus, enterovirus, and Campylobacter infections correlated positively with GBS incidence. Conclusion: The overall GBS incidence decreased in the early stages of the COVID-19 pandemic, which can be attributed to the dramatic reduction in viral illnesses due to public measures.

Ramie leaf Extract Alleviates Bone Loss in Ovariectomized Rats-The Involvement of ROS and Its Associated Signalings.

Ramie leaf (Boehmeria nivea L.) has been traditionally used to treat gynecological and bone-related disorders. This study aims to evaluate the effect of Ramie leaf extracts (RLE) against osteoporosis in ovariectomized (OVX) rats. Female SD rats aged seven weeks were randomly assigned into five OVX and a sham-operated (sham) group. OVX subgroups include OVX, vehicle-treated OVX group; E2, OVX with 100 µg/kg 17ß-estradiol; and RLE 0.25, 0.5, and 1, OVX rats treated with 0.25, 0.5, and 1 g/kg/day RLE, respectively. Two weeks into the bilateral ovariectomy, all the rats were orally administered with or without RLE daily for 12 weeks. OVX rats administered with RLE showed higher bone density, relatively low tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and lower reactive oxygen species (ROS) within bone tissues compared to vehicle-treated OVX rats. Furthermore, supplementation of RLE improved bone mineral density (BMD) and bone microstructure in the total femur. RLE prevented RANKL-induced osteoclast differentiation and expression of osteoclastogenesis-related genes such as Cal-R, MMP-9, cathepsin K, and TRAP in RANKL-induced RAW264.7 cells. Moreover, RLE administration lowered the intracellular ROS levels by reducing NADPH oxidase 1 (NOX-1) and 4-hydroxynonenal (4HNE). These results suggest that RLE alleviates bone mass loss in the OVX rats by inhibiting osteoclastogenesis, where reduced ROS and its associated signalings were involved.

Lycium chinense Miller fruit extract lowers liver enzyme levels in subjects with mild hepatic dysfunction: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: In our previous study, we showed that Lycium chinense Miller fruit extract (LFE) exerted hepatoprotective effects in mice. In the current study, we examined the effect of LFE on liver enzyme levels in subjects with mild hepatic dysfunction. METHODS: A total of 90 subjects, aged 19 to 70 years old, with abnormal alanine aminotransferase (ALT) levels, were randomly placed into either an LFE (n = 45) treatment group or a placebo group (n = 45). During the 12-week clinical trial, subjects in each group received either LFE or placebo capsules, and were instructed to take four tablets per day (1760 mg/day). The primary outcome of the study was the changes of ALT and γ-glutamyltransferase (GGT) levels in each subject. The safety of LFE supplementation was assessed and adverse events were recorded. RESULTS: LFE supplementation for 12 weeks resulted in a significant reduction of ALT (P = 0.0498) and GGT (P = 0.0368) levels in comparison to the placebo. No clinically significant changes were observed in any safety parameters. CONCLUSION: These results suggest that LFE can be applied to subjects with mild hepatic dysfunction with no possible side effects. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRIS) as no. KCT0003985.

Pediatric Nondysraphic Intramedullary Lipoma : Report of Two Cases and Review of the Literature.

Pediatric nondysraphic intramedullary lipoma is very rare, and only limited cases have been reported. In the present case, we present two infant patients with these pathologies who were surgically treated. Previous literature on 20 patients with these diseases who had undergone surgical treatments was analyzed. Surgical treatment should be considered in most symptomatic patients, and laminoplastic laminotomy and internal debulking of the lipoma under intraoperative neurophysiological monitoring are mostly recommended.

Awareness of postural orthostatic tachycardia syndrome is required in adolescent syncope.

We investigated head-up tilt test (HUTT) results across age-groups in syncope/presyncope patients to establish pediatric postural orthostatic tachycardia syndrome (POTS) characteristics. We retrospectively reviewed syncope patients' medical records. Adolescents were defined as 10 to 19 years old, adults as 20 to 59 years old, and older individuals as ≥60 years old. From HUTT results, we determined POTS prevalence and differences among the age-groups. We included 147 adolescents, 269 adults, and 123 older patients. Seventy (13.0%) patients (61.4% females; median age: 20 [17-25] years) were diagnosed with POTS. The syndrome was more prevalent among adolescents (33 [22.4%]) than adults (37 [13.8%]), and was absent among older individuals. Affected adolescents had significantly lower resting diastolic blood pressure (DBP) and heart rate (HR), and converted to maximum HR more rapidly than adolescents without the syndrome during the passive phase. Adolescents with POTS demonstrated several unique characteristics compared to adults with and adolescents without this syndrome. POTS may be underrecognized among syncope and presyncope patients, among which 22.4% of adolescents were diagnosed with the syndrome. POTS should be considered when evaluating syncope patients.

Efficacy and safety evaluation of adjuvant auricular acupuncture for smoking cessation: A study protocol of randomized, assessor-blinded, pragmatic pilot trial.

BACKGROUND: Smoking negatively impacts public health. There are several treatments to quit smoking, and nicotine replacement treatment (NRT) reportedly doubles the smoking cessation rate, with some limitations. Acupuncture is an alternative option with proven effects on smoking cessation. However, there has been no definite report that indicates the efficacy and safety of auricular acupuncture (AA) combined with NRT on smoking cessation. METHODS: This is a randomized, assessor-blind, and pragmatic pilot study. We will recruit 40 participants who want to stop smoking and randomly allocate them into an NRT group and an NRT + AA group with a 1:1 ratio. Participants will receive NRT for 4 weeks and the NRT + AA group will receive additional AA treatment with 5 AA points (Shenmen (TF4), lung (CO14), throat (TF3), inner nose (TG4), and endocrine (CO18)) twice a week for 4 weeks. Follow-up will be conducted 1 and 3 months after intervention completion. The primary outcome will be tobacco consumption and abstinence rate determined by calculating the rate of change in cigarette use and a urine test. Secondary outcomes will be the quality of life (EuroQol-5D and visual analogue scale), nicotine dependence (Fagerstrom test for nicotine dependence), nicotine withdrawal (Minnesota nicotine withdrawal scale), physical effects, satisfaction, and safety measurement (adverse events). RESULTS: We will investigate the efficacy and safety of AA combined with NRT treatment for smoking cessation. CONCLUSION: Our study will provide additional clinical evidence for AA as an adjuvant treatment for smoking cessation. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (registration number: KCT0007212).

Supplementation with Vitis vinifera Jingzaojing Leaf and Shoot Extract Improves Exercise Endurance in Mice.

Switching myofibers from the fast-glycolytic type to the slow-oxidative type is associated with an alleviation of the symptoms associated with various cardiometabolic diseases. This study investigates the effect of Vitis vinifera Jingzaojing leaf and shoot extract (JLSE), which is rich in phenolic compounds, on the regulation of skeletal muscle fiber-type switching, as well as the associated underlying mechanism. Male C57BL/6N mice were supplemented orally with vehicle or JLSE (300 mg/kg) and subjected to treadmill exercise training. After four weeks, mice in the JLSE-supplemented group showed significantly improved exercise endurance and mitochondrial oxidative capacity. JLSE supplementation increased the expression of sirtuin 6 and decreased Sox6 expression, thereby elevating the number of mitochondria and encouraging fast-to-slow myofiber switching. The results of our experiments suggest that JLSE supplementation reprograms myofiber composition to favor the slow oxidative type, ultimately enhancing exercise endurance.

MIR133A regulates cell proliferation, migration, and apoptosis by targeting SOX9 in human colorectal cancer cells.

The human microRNA 133A (MIR133A) was identified as a CRC-associated miRNA. It was down-regulated in human CRC tissues. We identified the putative MIR133A1 and A2 target genes by comparing the transcriptome analysis data of MIR133A1 and A2 knock-in cells with the candidate MIR133A target genes predicted by bioinformatics tools. We identified 29 and 33 putative MIR133A and A2 direct target genes, respectively. Among them, we focused on the master transcription regulator gene SRY-box transcription factor 9 (SOX9), which exhibits a pleiotropic role in cancer. We confirmed that SOX9 is a direct target gene of MIR133A by luciferase reporter assay, quantitative RT-PCR, and western blot analysis. Overexpression of MIR133A in CRC cell lines significantly decreased SOX9 and its downstream PIK3CA-AKT1-GSK3B-CTNNB1 and KRAS-BRAF-MAP2K1-MAPK1/3 pathways and increased apoptosis. Furthermore, functional studies reveal that cell proliferation, colony formation, and migration ability were significantly decreased by MIR133A-overexpressed CRC cell lines. Knockdown of SOX9 in CRC cell lines by SOX9 gene silencing showed similar results. We also used a xenograft model to show that MIR133A overexpression suppresses tumor growth and proliferation. Our results suggest that MIR133A regulates cell proliferation, migration, and apoptosis by targeting SOX9 in human colorectal cancer.