Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology.

Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in the year 2000 in yeast. Two homologs of Atg9, ATG9A and ATG9B, have been found in mammals. While ATG9B shows a tissue-specific expression pattern, such as in the placenta and pituitary gland, ATG9A is ubiquitously expressed. Additionally, ATG9A deficiency leads to severe defects not only at the molecular and cellular levels but also at the organismal level, suggesting key and fundamental roles for ATG9A. The subcellular localization of ATG9A on small vesicles and its functional relevance to autophagy have suggested a potential role for ATG9A in the lipid supply during autophagosome biogenesis. Nevertheless, the precise role of ATG9A in the autophagic process has remained a long-standing mystery, especially in neurons. Recent findings, however, including structural, proteomic, and biochemical analyses, have provided new insights into its function in the expansion of the phagophore membrane. In this review, we aim to understand various aspects of ATG9 (in invertebrates and plants)/ATG9A (in mammals), including its localization, trafficking, and other functions, in nonneuronal cells and neurons by comparing recent discoveries related to ATG9/ATG9A and proposing directions for future research.Abbreviation: AP-4: adaptor protein complex 4; ATG: autophagy related; cKO: conditional knockout; CLA-1: CLArinet (functional homolog of cytomatrix at the active zone proteins piccolo and fife); cryo-EM: cryogenic electron microscopy; ER: endoplasmic reticulum; KO: knockout; PAS: phagophore assembly site; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SV: synaptic vesicle; TGN: trans-Golgi network; ULK: unc-51 like autophagy activating kinase; WIPI2: WD repeat domain, phosphoinositide interacting 2.

Association between high-sensitivity C-reactive protein and renal function in Korean adults: A sex-specific analysis of Korea National Health and Nutrition Examination Survey 2015 to 2018 data.

This study aimed to investigate the association between high-sensitivity C-reactive protein (hs-CRP) levels, as a surrogate marker of systemic inflammation, and renal function among Korean adults grouped by age, sex, and body mass index. This study analyzed data obtained from the Korea National Health and Nutrition Examination Survey 2015 to 2018, a cross-sectional and nationally representative survey conducted by the Korean Centers for Disease Control and Prevention. Of the 22,451 subjects included in this study, 19,607 (87.3%) and 2844 (12.7%) had normal kidney function and incident chronic kidney disease, respectively. Reduced renal function was more frequently observed in subjects with high hs-CRP levels than in those with low hs-CRP levels (odds ratio [OR], 1.438; 95% confidence interval [CI], 1.234-1.674). In the group aged ≥ 65 years, the odds of reduced renal function were higher among subjects with a high hs-CRP level compared to those with a low hs-CRP level (OR, 1.528; 95% CI, 1.191-1.960). The association between hs-CRP level and renal function was observed only in women (OR, 2.485; 95% CI, 1.779-3.470) and further stratified by age and sex, the odds of reduced renal function were likely higher in women aged ≥ 65 years with a high hs-CRP level (OR, 2.338; 95% CI, 1.622-3.369). Moreover, reduced renal function was more observed in subjects aged ≥ 65 years and those with a body mass index < 25 kg/m2 (OR, 1.502; 95% CI, 1.087-2.075). This study showed that a high hs-CRP level likely contributes to the increased prevalence of reduced renal function. This association may aid the identification of individuals at high risk for reduced renal function, especially elderly women, in clinical or public health practice.

Successful treatment with rituximab in anti-phospholipid syndrome nephropathy associated with systemic lupus erythematosus: A case report and literature review.

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency.

Evaluating the effectiveness of mitigation measures in environmental impact assessments: A comprehensive review of development projects in Korea.

Rapid urbanization and development projects in Korea have posed significant threats to biodiversity; thus, effective mitigation measures are required to preserve natural habitats. Nevertheless, the factors underlying variations in mitigation measure effectiveness according to the disturbance level and surrounding environmental conditions have not been clarified. This study evaluated the effectiveness of mitigation measures implemented in environmental impact assessments (EIAs) of development projects in Korea, with a focus on their effectiveness with respect to the disturbance level and surrounding environmental conditions. A review of 288 EIA reports from selected projects that implemented all 10 mitigation measures classified according to the Wildlife Conservation Comprehensive Plan was conducted. Using the biodiversity tipping point framework, the effects of mitigation measures on biodiversity were categorized into four levels and analyzed. Analysis of variance and redundancy analysis were then performed to discern the variance in mitigation measure effectiveness in terms of the disturbance level, surrounding environment, and species. The results revealed significant variations in the effectiveness of mitigation measures depending on the surrounding environment and disturbance level. Linear projects exhibited a clear impact on various species as the disturbance level increased, whereas area-based projects did not exhibit such pronounced effects. All species demonstrated a negative relationship with development duration, development area, and distance from urban centers. Notably, avian and amphibian species showed a strong negative correlation with the digital elevation model while reptiles and mammals exhibited a strong positive relationship with pre-development biodiversity and distance from protected areas, respectively. Mitigation measures play a key role in alleviating the adverse effects of development projects; therefore, our findings indicate the need for spatially tailored mitigation plans to augment their effectiveness.

Phosphate level predicts mortality in acute kidney injury patients undergoing continuous kidney replacement therapy and has a U-shaped association with mortality in patients with high disease severity: a multicenter retrospective study.

BACKGROUND: This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. METHODS: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. RESULTS: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21-1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78-2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09-1.99; p = 0.01) but not among those with low disease severity. CONCLUSION: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Clinical Outcomes of Solid Organ Transplant Recipients Hospitalized with COVID-19: A Propensity Score-Matched Cohort Study.

BACKGROUND: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. MATERIALS AND METHODS: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. RESULTS: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization (P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12-4.11) and male gender (OR, 2.62; 95% CI, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24-0.79) was associated with better outcomes. CONCLUSION: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Autophagy caused by oxidative stress promotes TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Rottlerin Enhances the Autophagic Degradation of Phosphorylated Tau in Neuronal Cells.

Intra-neuronal accumulation of hyper-phosphorylated tau as neurofibrillary tangles (NFT) is a hallmark of Alzheimer's disease (AD). To prevent the aggregation of phosphorylated tau in neurons, decreasing the phosphorylated tau protein levels is important. Here, we examined the biological effects of rottlerin, a phytochemical compound extracted from the Kamala tree, Mallotus philippinensis, on phosphorylated tau levels. Notably, rottlerin decreased the levels of intracellular phosphorylated and total tau. A marked increase in the LC3-II, a hallmark of autophagy, was observed in these cells, indicating that rottlerin strongly induced autophagy. Interestingly, rottlerin induced the phosphorylation of Raptor at S792 through the activation of adenosine-monophosphate activated-protein kinase (AMPK), which likely inhibits the mammalian target of rapamycin complex 1 (mTORC1), thus resulting in the activation of transcription factor EB (TFEB), a master regulator of autophagy. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) activity increased in the presence of rottlerin. The decrease of phosphorylated tau levels in the presence of rottlerin was ameliorated by the knockdown of TFEB and partially attenuated by the knockout of the Nrf2 gene. Taken together, rottlerin likely enhances the degradation of phosphorylated tau through autophagy activated by TFEB and Nrf2. Thus, our results suggest that a natural compound rottlerin could be used as a preventive and therapeutic drug for AD.

Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Healthy and Unhealthy Dietary Patterns of Depressive Symptoms in Middle-Aged Women.

Depressive symptoms are a common menopausal feature in middle-aged women and are associated with dietary factors. This study aimed to determine the association between dietary patterns and depressive symptoms in 2190 Korean women aged 45-69 years. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and food intake was examined using a food frequency questionnaire. Dietary patterns were derived from principal components analysis and identified two dietary patterns: a "healthy" dietary pattern (high intake of whole-grain rice, legumes, vegetables, fruits, and fish) and an "unhealthy" dietary pattern (high intake of noodles, dumplings, sweets, red meat, soda, and coffee). After adjusting for all confounding factors, those with the highest healthy dietary pattern scores had a 0.56-fold lower risk of depressive symptoms than those with the lowest score (Odds Ratio (OR) = 0.56, 95% confidence interval (CI): 0.37-0.84, p for trend = 0.006). Conversely, those with the highest unhealthy pattern scores had a 1.85-fold higher risk of depressive symptoms than that of those in the lowest quartile (OR = 1.85, 95% CI: 1.30-2.63, p for trend = 0.002). In middle-aged women, a dietary pattern of high intake of fiber-rich whole-grain rice, fruits, vegetables, and legumes may help prevent and manage depressive symptoms.

Rapid discrimination of Panax ginseng powder adulterated with various root plants by FT-IR spectroscopy coupled with multivariate analysis.

Panax ginseng powder adulterated with other root plants (arrowroot, bellflower, and lance asiabell) was discriminated using Fourier transform infrared (FT-IR) spectroscopy, combined with multivariate analysis. Principal component analysis visually diagnosed the adulteration by showing two distinct clusters based on presence of adulteration. Wavenumber regions (1000 cm-1 and 3300 cm-1) selected from the loading plot associated with the vibration of OH and CH bond in ginsenoside and aromatic compounds. A quantitative model for the content of ginsenosides and specific aromatic compounds as indicators of pure ginseng powder, was developed based on partial least square regression analysis. The performance of the prediction model preprocessed with the Savizky-Golay 1st derivative was improved to R2 of 0.9650, 0.9635, and 0.9591 for Rb1, Rc, and ß-Panasinsene, respectively. Therefore, FT-IR technology makes it possible to rapidly authenticate pure ginseng product based on the ginsenoside contents and aroma compound.

Severe Acute Kidney Injury Associated with Transformation of Chronic Myelomonocytic Leukemia into Acute Myeloid Leukemia: A Case Report.

Chronic myelomonocytic leukemia (CMML) is a rare hematologic disorder that infrequently causes acute kidney injury (AKI). CMML can transform into acute myeloid leukemia (AML), which can be accompanied by a deterioration in kidney function. However, severe AKI due to extramedullary manifestations of AML is rare. Herein, we present the case of a 67-year-old male patient with CMML that transformed into AML with severe AKI necessitating hemodialysis. The cause of the AKI was the AML transformation. The patient, with stable kidney function after chemotherapy for CMML, presented with a sudden decline in kidney function. Hemodialysis was initiated because of severe AKI, and histopathologic evaluation of the kidney biopsy specimen revealed severe, diffuse mixed inflammatory cell infiltrates in the interstitium and c-kit-immunopositive myeloblast-like cells. A bone marrow biopsy was performed because of the kidney biopsy findings suggesting that leukemic infiltration led to the diagnosis of AML. The patient received chemotherapy for AML, and his kidney function recovered. As illustrated in this case, severe AKI can develop as an early extramedullary manifestation during transformation from CMML to AML. Therefore, in patients with CMML and rapidly declining renal function, transformation into AML should be considered and histopathologically confirmed by kidney biopsy.

Changes in bacterial composition and metabolite profiles during kimchi fermentation with different garlic varieties.

Garlic, a key ingredient in kimchi, is an indispensable source of lactic acid bacteria, which are essential for fermentation. This study explored the effects of various garlic varieties on kimchi fermentation, focusing on changes in microbial communities and metabolite profiles. We observed that the type of garlic used did not significantly alter the microbial community. However, the presence of garlic itself made a significant difference. Specifically, kimchi with garlic showed higher abundance of Leuconostoc and Weissella, which are bacteria primarily responsible for kimchi fermentation. Additionally, kimchi containing garlic had increased levels of mannitol and fructose, which significantly influence taste; however, lactic acid and putrescine levels were decreased. Therefore, the addition of garlic directly contributes to the flavor profile of kimchi. Sixty-two metabolites were identified using gas chromatography and mass spectrometry. The variety of garlic added influenced the metabolite profiles of kimchi, particularly in the later stages of fermentation. These profiles were categorized based on the garlic's origin, whether from southern or northern ecotypes (R2X = 0.933, R2Y = 0.986, Q2 = 0.878). These findings confirm that both the presence and the variety of garlic significantly impact the microbial ecology and metabolites during kimchi fermentation, underscoring its essential role in the process.

Investigation of Metabolite Differences in Salted Shrimp Varieties during Fermentation.

Fermentation of salted shrimp involves the interaction of multiple factors. However, studies of the effects of shrimp variety and fermentation temperature on metabolites generated during fermentation are limited. Therefore, we investigated the effects of the shrimp variety, fermentation temperature, and fermentation period on the composition of fermented salted shrimp. Four different varieties of salted shrimp, namely, Detteugijeot (SSA), Red shrimp jeot (SSB), Chujeot (SSC), and Yukjeot (SSD), were prepared and stored at 5 and 10 °C for 5 months. The pH values ranged from 6.71 to 6.99, with SSD showing the lowest pH at both temperatures. Although total nitrogen content remained relatively constant, amino nitrogen exhibited an upward trend after 2 months and was particularly increased at 10 °C. This increase was attributed to variations in microorganisms and enzymes in the salted shrimp. Except for proline, citrulline, and ornithine, amino acid levels increased during fermentation with the highest amounts detected in SSA. Additionally, the levels of glutamic acid and branched-chain amino acids were found to be sensitive to fermentation temperature. Amino acid levels were apparently affected by species-specific metabolic pathways of the microorganisms present in each salted shrimp. Compared to the other varieties, SSB had significantly higher contents of adenosine triphosphate and hypoxanthine. A high hypoxanthine content could contribute to increased bitterness and an umami taste profile. Furthermore, the correlation between salted shrimp and metabolites was unique in SSB, whereas partial clustering was observed between the SSA and SSC.

Effects of C-Peptide on Dexamethasone-Induced In Vitro and In Vivo Models as a Potential Therapeutic Agent for Muscle Atrophy.

This study aimed to investigate the effects of C-peptide on C2C12 myotubes and a mouse model. Both in vitro and in vivo experiments were conducted to elucidate the role of C-peptide in muscle atrophy. Various concentrations (0, 0.01, 0.1, 1, 10, and 100 nM) of C-peptide were used on the differentiated C2C12 myotubes with or without dexamethasone (DEX). C57BL/6J mice were administered with C-peptide and DEX for 8 days, followed by C-peptide treatment for 12 days. Compared to the DEX group, C-peptide increased the fusion and differentiation indices and suppressed atrophic factor expression in C2C12 myotubes. However, 100 nM C-peptide decreased the fusion and differentiation indices and increased atrophic factor expression regardless of DEX treatment. In C57BL/6J mice, DEX + C-peptide co-treatment significantly attenuated the body and muscle weight loss and improved the grip strength and cross-sectional area of the gastrocnemius (Gas) and quadriceps (Quad) muscles. C-peptide downregulated the mRNA and protein levels of muscle degradation-related markers, particularly Atrogin-1, in Gas and Quad muscles. This study underscores the potential of C-peptides in mitigating muscle weight reduction and preserving muscle function during muscle atrophy via molecular regulation. In addition, the work presents basic data for future studies on the effect of C-peptide on diabetic muscular dystrophy.

Mentha canadensis attenuates adiposity and hepatic steatosis in high-fat diet-induced obese mice.

BACKGROUND/OBJECTIVES: Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. MATERIALS/METHODS: Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. RESULTS: The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. CONCLUSIONS: These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.

Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy.

Background: Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients from the total population who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.

Analysis of the association between osteoporosis and muscle strength in Korean adults: a national cross-sectional study.

BACKGROUND: This study aimed to examine the associations between osteoporosis and hand grip strength (HGS), a surrogate marker of muscular strength, among Korean adults stratified by body mass index (BMI), age, and renal function. METHODS: This study was conducted using the data obtained from the Korea National Health and Nutrition Examination Survey 2015-2019, a cross-sectional and nationally representative survey performed by the Korea Centers for Diseases Control and Prevention. RESULTS: Of the 26,855 subjects included in this study, those with low muscle strength (LMS) and normal muscle strength were showed in 4,135 (15.4%) and 22,720 (84.6%) subjects, respectively. The osteoporotic subjects had a higher prevalence rate for LMS than those without osteoporosis after adjusting for age [odds ratio (OR), 1.684; 95% confidence interval (CI), 1.500-1.890). The subjects with osteoporosis and BMI < 18.5 kg/m2 also had a higher prevalence rate for LMS after adjusting for age compared to those with non-osteoporosis and BMI < 18.5 kg/m2 (OR, 1.872; 95% CI, 1.043-3.359). Compared to the non-osteoporotic subjects with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, those with osteoporosis and eGFR ≥ 60 mL/min/1.73 m2 had a higher prevalence rate for LMS after controlling for age and sex (OR, 1.630; 95% CI, 1.427-1.862). CONCLUSIONS: The results showed that osteoporosis was likely to contribute to an increased prevalence rate of LMS in terms of HGS. Aging, BMI, and renal function also had significant effects on the association between osteoporosis and LMS. This association is likely to assist in developing better strategies to estimate bone health in clinical or public health practice.