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Background/Objectives: This study aimed to evaluate bone mineral density (BMD) discordance and its implications in veterans with unilateral lower-limb amputation, emphasizing the need for comprehensive hip assessments. Methods: Data were collected from 84 male veterans, and BMD was measured using dual-energy X-ray absorptiometry (DXA) at the lumbar spine, intact hip, and amputated hip. Results: The T-scores for the lumbar spine, intact hip, and amputated hip were -0.27 ± 1.69, -0.25 ± 1.20, and -1.07 ± 1.33, respectively. Osteoporosis and osteopenia were present in 19% and 34.6% of patients, respectively. Osteopenia and osteoporosis were most prevalent in the hips on the amputated side (32.1% and 13.1%, respectively), followed by the lumbar spines (22.6% and 8.3%) and the hips on the intact side (17.9% and 2.4%). BMD discordance between the lumbar spine and hip was found in 47.6% of participants, while discordance between both hips was observed in 39.3%. Transfemoral amputees had significantly lower BMD at the amputated hip compared to transtibial amputees (-2.38 ± 1.72 vs. -0.87 ± 1.16, p < 0.001). Conclusions: Veterans with unilateral lower-limb amputation exhibit a high prevalence of osteoporosis and significant BMD discordance, particularly between both hips. These findings underscore the necessity for bilateral hip assessments to ensure the accurate diagnosis and effective management of osteoporosis in this population.
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Cachexia is associated with various diseases, such as heart disease, infectious disease, and cancer. In particular, cancer-associated cachexia (CAC) accounts for more than 20% of mortality in cancer patients worldwide. Adipose tissue in CAC is characterized by adipocyte atrophy, mainly due to excessively increased lipolysis and impairment of adipogenesis. CAC is well known for the loss of skeletal muscle mass and/or fat mass. CAC induces severe metabolic alterations, including protein, lipid, and carbohydrate metabolism. The objectives of this study were to evaluate the effects of bee wax (Apis mellifera L. 1758) (BW) extract on adipogenesis, lipolysis, and mitochondrial oxygen consumption through white adipocytes, 3T3-L1. To achieve this study, cancer-associated cachexia condition was established by incubation of 3T3-L1 with colon cancer cell line CT26 cultured media. BW extract recovered the reduced adipogenesis under cachectic conditions in CT26 media. Treatment of BW showed increasing lipid accumulation as well as adipogenic gene expression and its target gene during adipogenesis. The administration of BW to adipocytes could decrease lipolysis. Also, BW could significantly downregulated the mitochondrial fatty acid oxidation-related genes, oxygen consumption rate, and extracellular acidification rate. Our results suggest that BW could improve metabolic disorders such as CAC through the activation of adipogenesis and inhibition of lipolysis in adipocytes, although we need further validation in vivo CAC model to check the effects of BW extract. Therefore, BW extract supplements could be useful as an alternative medicine to reverse energy imbalances.
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Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their structure and spatial distribution in the native context remain poorly characterized. Herein, we employ an integrative multimodal approach to elucidate the structural and functional organization of plasma membrane protein complexes in Candida glabrata , focusing on prominent and essential membrane proteins, the polysaccharide synthase ß-(1,3)-glucan synthase (GS) and the proton pump Pma1. Cryo-electron tomography (cryo-ET) and live cell imaging reveal that GS and Pma1 are heterogeneously distributed into distinct plasma membrane microdomains. Treatment with caspofungin, an echinocandin antifungal that targets GS, alters the plasma membrane and disrupts the native distribution of GS and Pma1. Based on these findings, we propose a model for echinocandin action that considers how drug interactions with the plasma membrane environment lead to inhibition of GS. Our work underscores the importance of interrogating the structural and dynamic characteristics of fungal plasma membrane proteins in situ to understand function and facilitate precisely targeted development of novel antifungal therapies.
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Regulatory T cells (Tregs) residing in visceral adipose tissue (VAT) play a pivotal role in regulating tissue inflammation and metabolic dysfunction associated with obesity. However, the specific phenotypic and functional characteristics of Tregs in obese VAT, as well as the regulatory mechanisms shaping them, remain elusive. This study demonstrates that obesity selectively reduces Tregs in VAT, characterized by restrained proliferation, heightened PD-1 expression, and diminished ST2 expression. Additionally, obese VAT displays distinctive maturation of dendritic cells (DCs), marked by elevated expressions of MHC-II, CD86, and PD-L1, which are inversely correlated with VAT Tregs. In an in vitro co-culture experiment, only obese VAT DCs, not macrophages or DCs from subcutaneous adipose tissue (SAT) and spleen, result in decreased Treg differentiation and proliferation. Furthermore, Tregs differentiated by obese VAT DCs exhibit distinct characteristics resembling those of Tregs in obese VAT, such as reduced ST2 and IL-10 expression. Mechanistically, obesity lowers IL-33 production in VAT DCs, contributing to the diminished Treg differentiation. These findings collectively underscore the critical role of VAT DCs in modulating Treg generation and shaping Treg phenotype and function during obesity, potentially contributing to the regulation of VAT Treg populations.
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Interleucina-33 , Linfócitos T Reguladores , Humanos , Linfócitos T Reguladores/metabolismo , Interleucina-33/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Obesidade/metabolismo , Células Dendríticas/metabolismoRESUMO
The ultrahigh surface area of two-dimensional materials can drive multimodal coupling between optical, electrical, and mechanical properties that leads to emergent dynamical responses not possible in three-dimensional systems. We observed that optical excitation of the WS2 monolayer above the exciton energy creates symmetrically patterned mechanical protrusions which can be controlled by laser intensity and wavelength. This observed photostrictive behavior is attributed to lattice expansion due to the formation of polarons, which are charge carriers dressed by lattice vibrations. Scanning Kelvin probe force microscopy measurements and density functional theory calculations reveal unconventional charge transport properties such as the spatially and optical intensity-dependent conversion in the WS2 monolayer from apparent n- to p-type and the subsequent formation of effective p-n junctions at the boundaries between regions with different defect densities. The strong opto-electrical-mechanical coupling in the WS2 monolayer reveals previously unexplored properties, which can lead to new applications in optically driven ultrathin microactuators.
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Recent studies have increasingly focused on the occurrence of plastic leachate and its impacts on aquatic ecosystems. Nonetheless, the environmental fate of this leachate in the presence of abundant natural organic matter (NOM)-a typical scenario in environments contaminated with plastics-remains underexplored. This study investigates the photo-induced leaching behaviors of dissolved organic matter (DOM) from terrestrial-sourced particles (forest soil and leaf litter) and microplastics (MPs), specifically polystyrene (PS) and polyvinyl chloride (PVC), over a two-week period. We also examined the biodegradability and spectroscopic characteristics of the leached DOM from both sources. Our results reveal that DOM from microplastics (MP-DOM) demonstrates more persistent leaching behavior compared to terrestrial-derived DOM, even with lesser quantities per unit of organic carbon. UV irradiation was found to enhance DOM leaching across all particle types. However, the photo-induced leaching behaviors of fluorescent components varied with the particle type. The MP group exhibited a broader range and higher biodegradability (ranging from 19.7% to 61.6%) compared to the terrestrial-sourced particles (ranging from 3.7% to 16.5%). DOM leached under UV irradiation consistently showed higher biodegradability than that under dark conditions. Furthermore, several fluorescence characteristics of DOM, such as the protein/phenol-like component (%C2), terrestrial humic-like component (%C3), and humification index (HIX)-traditionally used to indicate the biodegradability of natural organic matter-were also effective in assessing MP-DOM (with correlation coefficients R2 = 0.6055 (p = 0.003), R2 = 0.5389 (p = 0.007), and R2 = 0.4640 (p = 0.015), respectively). This study provides new insights into the potential differences in environmental fate between MP-DOM and NOM in aquatic environments heavily contaminated with MPs.
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Microplásticos , Plásticos , Matéria Orgânica Dissolvida , Ecossistema , Solo/química , Substâncias Húmicas/análise , Espectrometria de Fluorescência/métodosRESUMO
Numerous studies have focused on the interaction between microplastics (MPs) and phenanthrene (PHE) in aquatic environments. However, the intricate roles of aquatic humic substances (HS), which vary with environmental conditions, in influencing PHE-MP interactions are not yet fully understood. This study investigates the variable and environmentally sensitive roles of HS in modifying the interactions between PHE and polyethylene (PE) MPs under laboratory-simulated aquatic conditions with varying solution chemistry, including pH, HS types, HS concentrations, and ionic strength. Our findings show that the presence of HS significantly reduces the adsorption of PHE onto both pristine and aged PE MPs, with a more pronounced reduction observed in aged PEs. This effect is highlighted by a notable decrease in the partitioning coefficient (Kd) of PHE, which falls from 2.60 × 104 to 1.30 × 104 L/kg on MPs in the presence of HS. The study also demonstrates that alterations in the net charge of HS solutions are crucial in modifying PHE distribution onto PEs. An initial decrease in Kd values at higher pH levels is reversed when HS is introduced. Furthermore, an increase in HS concentrations is associated with lower Kd values. In conditions of higher ionic strength, the retention of PHE by HS is intensified, likely due to an enhanced salting-out effect. This research highlights the significant role of aquatic HS in modulating the distribution of PHE in MP-polluted waters, which is highly influenced by various solution chemistry factors. The findings are vital for understanding the fate of PHE in MP-contaminated aquatic environments and can contribute to refining predictive models that consider diverse solution chemistry scenarios.
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Fenantrenos , Poluentes Químicos da Água , Microplásticos , Substâncias Húmicas/análise , Plásticos/química , Fenantrenos/análise , Polietileno , Poluentes Químicos da Água/análise , AdsorçãoRESUMO
Background: Intestinal epithelial cells (IECs) play a crucial role in regulating the symbiotic relationship between the host and the gut microbiota, thereby allowing them to modulate barrier function, mucus production, and aberrant inflammation. Despite their importance, establishing an effective ex vivo culture method for supporting the prolonged survival and function of primary IECs remains challenging. Here, we aim to develop a novel strategy to support the long-term survival and function of primary IECs in response to gut microbiota by employing mild reduction of disulfides on the IEC surface proteins with tris(2-carboxyethyl)phosphine. Methods: Recognizing the crucial role of fibroblast-IEC crosstalk, we employed a cell surface modification strategy, establishing layer-to-layer contacts between fibroblasts and IECs. This involved combining negatively charged chondroitin sulfate on cell surfaces with a positively charged chitosan thin film between cells, enabling direct intercellular transfer. Validation included assessments of cell viability, efficiency of dye transfer, and IEC function upon lipopolysaccharide (LPS) treatment. Results: Our findings revealed that the layer-by-layer co-culture platform effectively facilitates the transfer of small molecules through gap junctions, providing vital support for the viability and function of primary IECs from both the small intestine and colon for up to 5 days, as evident by the expression of E-cadherin and Villin. Upon LPS treatment, these IECs exhibited a down-regulation of Villin and tight junction genes, such as E-cadherin and Zonula Occludens-1, when compared to their nontreated counterparts. Furthermore, the transcription level of Lysozyme exhibited an increase, while Mucin 2 showed a decrease in response to LPS, indicating responsiveness to bacterial molecules. Conclusions: Our study provides a layer-by-layer-based co-culture platform to support the prolonged survival of primary IECs and their features, which is important for understanding IEC function in response to the gut microbiota.
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Controlled assembly of nanoparticles into well-defined assembled architectures through precise manipulation of spatial arrangement and interactions allows the development of advanced mesoscale materials with tailored structures, hierarchical functionalities, and enhanced properties. Despite remarkable advancements, the controlled assembly of highly anisotropic 2Dnanosheets is significantly challenging, primarily due to the limited availability of selective edge-to-edge connectivity compared to the abundant large faces. Innovative strategies are needed to unlock the full potential of 2D-nanomaterialsin self-assembled structures with distinct and desirable properties. This research unveils the discovery of controlled self-assembly of 2D-silica nanosheets (2D-SiNSs) into hollow micron-sized soccer ball-like shells (SA-SiMS). The assembly is driven by the physical flexibility of the 2D-SiNSs and the differential electricdouble-layer charge gradient creating electrostatic bias on the edge and face regions. The resulting SA-SiMS structures exhibit high mechanical stability, even at high-temperatures, and exhibit excellent performance as catalyst support in the dry reforming of methane. The SA-SiMS structures facilitate improved mass transport, leading to enhanced reaction rates, while the thin silica shell prevents sintering of small catalyst nanocrystals, thereby preventing coke formation. This discovery sheds light on the controllable self-assembly of 2D nanomaterials and provides insights into the design and synthesis of advanced mesoscale materials with tailored properties.
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Adipose tissue invariant natural killer T (iNKT) cells are a crucial cell type for adipose tissue homeostasis in obese animals. However, heterogeneity of adipose iNKT cells and their function in adipocyte turnover are not thoroughly understood. Here, we investigate transcriptional heterogeneity in adipose iNKT cells and their hierarchy using single-cell RNA sequencing in lean and obese mice. We report that distinct subpopulations of adipose iNKT cells modulate adipose tissue homeostasis through adipocyte death and birth. We identify KLRG1+ iNKT cells as a unique iNKT cell subpopulation in adipose tissue. Adoptive transfer experiments showed that KLRG1+ iNKT cells are selectively generated within adipose tissue microenvironment and differentiate into a CX3CR1+ cytotoxic subpopulation in obese mice. In addition, CX3CR1+ iNKT cells specifically kill enlarged and inflamed adipocytes and recruit macrophages through CCL5. Furthermore, adipose iNKT17 cells have the potential to secrete AREG, and AREG is involved in stimulating adipose stem cell proliferation. Collectively, our data suggest that each adipose iNKT cell subpopulation plays key roles in the control of adipocyte turnover via interaction with adipocytes, adipose stem cells, and macrophages in adipose tissue.
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Células T Matadoras Naturais , Camundongos , Animais , Células T Matadoras Naturais/metabolismo , Camundongos Obesos , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Obesidade/genética , Obesidade/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Thiazolidinedione, an insulin sensitizer, has beneficial effects on glucose metabolism; however, there are concerns regarding weight gain and heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce body weight, increase diuresis, and play a protective role in heart failure. We examined the complementary effects of dapagliflozin, an SGLT2 inhibitor, and lobeglitazone, a thiazolidinedione, in high-fat diet (HFD)-induced obese mice. We treated HFD-induced obese mice with vehicle, dapagliflozin, lobeglitazone, and their combination for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed after 12-week treatment, and body composition was measured by dual-energy X-ray absorptiometry before and after treatment. We analyzed oxygen consumption rate (OCR) using 3T3-L1 cells after treatment of ß-hydroxybutyrate and/or lobeglitazone. Treatment with a combination of dapagliflozin and lobeglitazone resulted in a significant decrease in postprandial hyperglycemia compared with dapagliflozin monotherapy, but not compared with lobeglitazone monotherapy. The addition of dapagliflozin to lobeglitazone treatment did not attenuate weight gain compared with lobeglitazone monotherapy in this study. However, this combination prevented the increase of organ weight of liver and heart, and OCR in 3T3-L1 cells was increased after treatment with a combination of ß-hydroxybutyrate and lobeglitazone compared to lobeglitazone monotherapy. We confirmed the beneficial effect of lobeglitazone on glucose metabolism; however, we did not find any beneficial effect of dapagliflozin on body weight in HFD-induced obese mice. However, the protective effects of dapagliflozin and lobeglitazone combined therapy on the liver, heart, energy consumption, and ß-cell senescence are worth investigating in clinical trials.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Tiazolidinedionas , Camundongos , Animais , Camundongos Obesos , Ácido 3-Hidroxibutírico , Glicemia/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Insulina/metabolismo , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Tiazolidinedionas/uso terapêutico , Modelos Animais de Doenças , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Aumento de Peso , Dieta Hiperlipídica/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
The environmental occurrence and impact of dissolved organic matter leached from microplastics (MP-DOM) has been the subject of increased research interest. Commercial plastics, which typically contain additives, are subject to natural weathering processes and can eventually lose their additives. However, the effects of organic additives in commercial microplastics (MPs) on the release of MP-DOM under UV irradiation remain poorly understood. In this study, four polymer MPs (polyethylene; PE, polypropylene; PP, polystyrene; PS, polyvinylchloride; PVC) and four commercial MPs, including a PE zip bag, a PP facial mask, a PVC sheet, Styrofoam, were subjected to leaching under UV irradiation, and the MP-DOM was characterized using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and fluorescence excitation emission matrix-parallel factor analysis (EEM-PARAFAC). Although UV light promoted the leaching of MP-DOM from both MP groups, the amount released was more pronounced for the polymer MPs than for the commercial MPs. The commercial MP-DOM was characterized by a prominent protein/phenol-like component (C1), while a humic-like component (C2) prevailed in the polymer MPs. FT-ICR-MS identified a higher number of unique molecular formulas for the commercial than for the polymer MP-DOM. The unique molecular formulas of commercial MP-DOM included known organic additives and other breakdown products, while the polymer MP-DOM featured more pronounced unsaturated carbon structures in its identified unique formulas. Several molecular-level parameters showed significant correlations with fluorescence properties, such as CHO formulas (%) with C1 and condensed aromatic structure (CAS-like, %) with C2, suggesting the potential application of fluorescent components as an optical descriptor for the complex molecular-level composition. This study also revealed the possible high environmental reactivity of both polymer MPs and fully weathered plastics due to the unsaturated structures generated in sunlit environments.
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Microplásticos , Plásticos , Matéria Orgânica Dissolvida , Substâncias Húmicas/análise , Polímeros , Espectrometria de Fluorescência/métodosRESUMO
Microplastics (MPs) biofilms in drinking water and wastewater treatment plants (DWTPs and WWTPs) have gained increasing attention due to their potential to come into close contact with humans. This review examines the fate of pathogenic bacteria, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs) in MP biofilms and their impacts on operations in DWTPs and WWTPs, as well as the associated microbial risks for ecology and human health. The literature shows that pathogenic bacteria, ARBs, and ARGs with high resistance can persist on MP surfaces and may escape treatment plants, contaminating drinking and receiving water. Nine potential pathogens, ARB, and ARGs can be retained in DWTPs and sixteen in WWTPs. While MP biofilms can improve the removal of MPs themselves, as well as the associated heavy metals and antibiotic compounds, they can also induce biofouling, hinder the effectiveness of chlorination and ozonation, and cause the formation of disinfection by-products. Furthermore, the operation-resistant pathogenic bacteria, ARB, and ARGs on MPs may have adverse impacts on receiving ecosystems, as well as human health, including a range of human diseases, from skin infections to pneumonia and meningitis. Given the significant implications of MP biofilms for aquatic ecosystems and human health, further research is necessary on the disinfection resistance of microbial populations in MP biofilm. This study provides valuable insights into the comprehensive understanding of the changes of MP biofilms in water and wastewater treatment systems as well as their impacts on ecology and human health.
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Plásticos , Purificação da Água , Humanos , Genes Bacterianos , Microplásticos , Antagonistas de Receptores de Angiotensina/farmacologia , Ecossistema , Antibacterianos/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Águas Residuárias , BiofilmesRESUMO
The prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.
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Microbioma Gastrointestinal , Mucinas , Humanos , Multiômica , Ecossistema , Bactérias/genéticaRESUMO
Lipid accumulation in hepatocytes can result from an imbalance between lipid acquisition and lipid catabolism. In recent years, it has been discovered that eicosanoids derived from arachidonic acid (AA) have the potential to create specialized pro-resolving lipid mediators to actively resolve inflammation, but it is not clear whether AA and lipoxygenases exert effects on hepatic inflammation. Here, the effects of atorvastatin on the expression of cytoplasmic phospholipase A2 (cPLA2) and lipoxygenase pathway genes (ALOX5, ALOX12, ALOX15, and ALOX15B) were evaluated in an in vitro model of palmitic acid (PA)-induced hepatocyte lipid accumulation in McA-RH7777 (McA) cells. Palmitic acid increased cPLA2 expression, intracellular AA levels, and ALOX12 expression (P < 0.05). Atorvastatin at various concentrations had no significant effects on AA levels or on cPLA2, ALOX15, and ALOX15B expressions. ALOX5 was not detected, despite multiple measurements. Pro-inflammatory IL-1ß expression levels were upregulated by PA (P < 0.01) and attenuated by atorvastatin (P < 0.001). TNFα did not differ among groups. The expression levels of anti-inflammatory IL-10 decreased in response to PA (P < 0.05), but were not affected by atorvastatin. In conclusion, in an in vitro model of lipid accumulation in McA cells, atorvastatin reduced IL-1ß; however, its effect was not mediated by AA and the lipoxygenase pathway at the established doses and treatment duration. Further research is required to investigate time-response data, as well as other drugs and integrated cell systems that could influence the lipoxygenase pathway and modulate inflammation in liver diseases.
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Lipoxigenase , Ácido Palmítico , Humanos , Atorvastatina/farmacologia , Lipoxigenase/genética , Inflamação/metabolismo , Lipoxigenases , Fosfolipases A2 Citosólicas/metabolismo , Hepatócitos/metabolismo , Expressão GênicaRESUMO
The physicochemical properties of biomaterials influence cell adhesion, shape, and polarization of macrophages. In this study, we aimed to evaluate the polarization of macrophages in terms of the regulation of cell adhesion and how synthetic mimics for heparin and poly(sodium-4-styrenesulfonate) can regulate macrophage polarization by modulating cell shape, focal adhesion, cell traction force, and intracellular tension. Our initial findings showed that macrophages cultured with heparin-mimicking polymer-based hydrogel matrix showed reduced expression of cell adhesion markers such as integrins, vinculin, RhoA, and ROCK1/2 and reduced cell shape, elongation, cell-matrix traction force, and intracellular tension. Furthermore, we observed a significant decrease in cell adhesion in cells cultured on the hydrogel, resulting in the promotion of M1 polarization. These findings offer insights into the important roles of cell-matrix interactions in macrophage polarization and offer a platform for heparin-mimicking polymer-based hydrogel matrices to induce M1 polarization by inducing cell adhesion without classical activators.
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Hidrogéis , Polímeros , Adesão Celular , Heparina/farmacologia , Heparina/metabolismo , Macrófagos/metabolismo , Polímeros/farmacologia , Polímeros/metabolismo , Materiais BiomiméticosRESUMO
The natural organic matter (NOM) properties in water from cold and hot mineral springs in South Korea are not well documented. We analyzed the characteristics of NOM in water from 25 cold and hot mineral springs located across South Korea. The NOM of each sample was concentrated using solid-phase extraction and analyzed using 15T Fourier-transform ion cyclotron resonance mass spectrometry. The origin of NOM was identified using van Krevelen diagrams. This study suggests that an analytical method to evaluate the characteristics of water in each region of South Korea can be established and used as a baseline for further research.
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Stress is an organism's response to a biological or psychological stressor, a method of responding to threats. The autonomic nervous system and hypothalamic-pituitary-adrenal axis (HPA axis) regulate adaptation to acute stress and secrete hormones and excitatory amino acids. This process can induce excessive inflammatory reactions to the central nervous system (CNS) by HPA axis, glutamate, renin-angiotensin system (RAS) etc., under persistent stress conditions, resulting in neuroinflammation. Therefore, in order to treat stress-related neuroinflammation, the improvement effects of several mechanisms of receptor antagonist and pharmacological anti-inflammation treatment were studied. The N-methyl-D-aspartate (NMDA) receptor antagonist, peroxisome proliferator-activated receptor agonist, angiotensin-converting enzyme inhibitor etc., effectively improved neuroinflammation. The interesting fact is that not only can direct anti-inflammation treatment improve neuroinflammation, but so can stress reduction or pharmacological antidepressants. The antidepressant treatments, including selective serotonin reuptake inhibitors (SSRI), also helped improve stress-related neuroinflammation. It presents the direction of future development of stress-related neuroinflammation drugs. Therefore, in this review, the mechanism of stress-related neuroinflammation and pharmacological treatment candidates for it were reviewed. In addition, treatment candidates that have not yet been verified but indicate possibilities were also reviewed.
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BACKGROUND: The effects of some drugs, aging, cancers, and other diseases can cause muscle wasting. Currently, there are no effective drugs for treating muscle wasting. In this study, the effects of ginsenoside Rd (GRd) on muscle wasting were studied. METHODS: Tumour necrosis factor-alpha (TNF-α)/interferon-gamma (IFN-γ)-induced myotube atrophy in mouse C2C12 and human skeletal myoblasts (HSkM) was evaluated based on cell thickness. Atrophy-related signalling, reactive oxygen species (ROS) level, mitochondrial membrane potential, and mitochondrial number were assessed. GRd (10 mg/kg body weight) was orally administered to aged mice (23-24 months old) and tumour-bearing (Lewis lung carcinoma [LLC1] or CT26) mice for 5 weeks and 16 days, respectively. Body weight, grip strength, inverted hanging time, and muscle weight were assessed. Histological analysis was also performed to assess the effects of GRd. The evolutionary chemical binding similarity (ECBS) approach, molecular docking, Biacore assay, and signal transducer and activator of transcription (STAT) 3 reporter assay were used to identify targets of GRd. RESULTS: GRd significantly induced hypertrophy in the C2C12 and HSkM myotubes (average diameter 50.8 ± 2.6% and 49.9% ± 3.7% higher at 100 nM, vs. control, P ≤ 0.001). GRd treatment ameliorated aging- and cancer-induced (LLC1 or CT26) muscle atrophy in mice, which was evidenced by significant increases in grip strength, hanging time, muscle mass, and muscle tissue cross-sectional area (1.3-fold to 4.6-fold, vs. vehicle, P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). STAT3 was found to be a possible target of GRd by the ECBS approach and molecular docking assay. Validation of direct interaction between GRd and STAT3 was confirmed through Biacore analysis. GRd also inhibited STAT3 phosphorylation and STAT3 reporter activity, which led to the inhibition of STAT3 nuclear translocation and the suppression of downstream targets of STAT3, such as atrogin-1, muscle-specific RING finger protein (MuRF-1), and myostatin (MSTN) (29.0 ± 11.2% to 84.3 ± 30.5%, vs. vehicle, P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). Additionally, GRd scavenged ROS (91.7 ± 1.4% reduction at 1 nM, vs. vehicle, P ≤ 0.001), inhibited TNF-α-induced dysregulation of ROS level, and improved mitochondrial integrity (P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). CONCLUSIONS: GRd ameliorates aging- and cancer-induced muscle wasting. Our findings suggest that GRd may be a novel therapeutic agent or adjuvant for reversing muscle wasting.