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Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future.
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Células Endoteliais , Fígado , Humanos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Animais , Fígado/metabolismo , Fígado/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologiaRESUMO
BACKGROUND AND AIMS: Metabolic diseases are globally popular, and a systematic review and meta-analysis of turmeric and curcuminoids on glucose metabolism among people with metabolic diseases was performed. DESIGN: We comprehensively searched Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, the Cochrane Library and two Chinese databases, Wanfang and CNKI for RCTs that focused on the effects of turmeric and curcuminoids on fasting blood glucose (FBG), hemoglobin A1C (HbA1c), fasting serum insulin (FSI) and HOMA-IR among patients with metabolic diseases. The FBG and HbA1c were the main outcomes to be analyzed. With random-effects models, separate meta-analyses were conducted by inverse-variance and reported as WMD with 95% CIs. RESULTS: Evidence from 17 RCTs including 22 trials showed that turmeric and curcuminoids lowered FBG by - 7.86 mg/dL (95% CI: -12.04, -3.67 mg/dL; P = 0.0002), HbA1c by - 0.38% (95% CI: -0.52%, -0.23%; P < 0.00001) and HOMA-IR by - 1.01 (95% CI: -1.6, -0.42; P = 0.0008). Moreover, they decreased fasting serum insulin by - 1.69 mU/L (95% CI: -3.22, -0.16 mU/L; P = 0.03) after more than 8 weeks of intervention in a subgroup analysis. CONCLUSIONS: Turmeric and curcuminiods decrease FBG, HbA1c and HOMA-IR significantly among subjects with metabolic disease. Additionally, they may have an effect on FSI concentrations if the intervention period is more than 8 weeks. However, attention should be paid to these outcomes due to the significant heterogeneity.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Metabólicas , Glicemia/metabolismo , Curcuma , Diarileptanoides , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina , Doenças Metabólicas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
ABSTRACT: Botanic drugs are reportedly effective in treating ischemic conditions by improving vascular circulation. However, it has been very rare for biomaterial researchers to look into the possibility of using such products in the context of tissue regeneration. This work studied 4 botanic drugs to explore their effects on vascular endothelial cell growth. Human umbilical endothelial cells were cultured in the presence of different doses of astragalus powder extract, astragalus injection, puerarin injection, and proanthocyanidin (PAC). Among the 4 drugs, PAC showed a potent effect on cell viability and stimulated cell growth in a dose-dependent manner. In particular, the PAC under test was able to maintain a high level of cell viability/proliferation comparable with the cells supplemented with the endothelial cell growth medium, at both low and normal serum conditions. Blocking either endothelial cell growth factor receptors or epithelial cell growth factor receptors was ineffective in reducing the stimulatory effect. The PAC released from polyvinyl alcohol cryogels stimulated HUVECs proliferation. The chick embryo chorioallantoic membrane model was further used to test the angiogenicity of PAC, showing that this botanic drug was potent in stimulating vasculature development. This work therefore demonstrates for the first time that PAC is capable of upregulating endothelial cell activity and growth in vitro in the absence of growth factors and that PAC can be loaded and released from drug carriers and can stimulate angiogenesis. These findings suggest the application of PAC in angiogenesis and tissue regeneration.
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Proantocianidinas , Inibidores da Angiogênese/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Embrião de Galinha , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica , Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1ß and TNF-α in the serum and downregulated nuclear factor κB expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.
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Berberina , Diabetes Mellitus Experimental , Acetilcolinesterase , Animais , Berberina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Glucose , Neuroimunomodulação , Ratos , Receptor Nicotínico de Acetilcolina alfa7RESUMO
BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.
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COVID-19/epidemiologia , COVID-19/mortalidade , Síndromes do Eutireóideo Doente/epidemiologia , SARS-CoV-2 , Tireotropina/sangue , Tiroxina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , Estudos de Coortes , Comorbidade , Síndromes do Eutireóideo Doente/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tireotropina/deficiência , Tiroxina/deficiênciaRESUMO
INTRODUCTION: Trimethylamine N-oxide (TMAO) is a metabolite produced by gut bacteria. Although increased TMAO levels have been linked to hypertension (HTN) and chronic kidney disease (CKD) with poor prognosis, no clinical studies have directly addressed the relationship between them. In this study, we investigated the relationship between TMAO and renal dysfunction in hypertensive patients. METHODS: We included healthy controls (n = 50), hypertensive patients (n = 46), and hypertensive patients with renal dysfunction (n = 143). Their blood pressure values were taken as the highest measured blood pressure. Renal function was evaluated using the estimated glomerular filtration rate. Plasma TMAO levels were measured using high-performance liquid chromatography tandem mass spectrometry. RESULTS: We found significant differences in plasma TMAO levels among the 3 groups (p < 0.01). The plasma TMAO of patients with HTN was significantly higher than that of healthy people, and the plasma TMAO of patients with HTN complicated by renal dysfunction was significantly higher than either of the other groups. Patients in the highest TMAO quartile were at a higher risk of developing CKD stage 5 than those in the lowest quartile. In the receiver operating characteristic curve, the area under the curve of TMAO combined with ß 2-macroglobulin for predicting renal dysfunction in patients with HTN was 0.85 (95% confidence interval 0.80-0.90). CONCLUSION: An elevated TMAO level reflects higher levels of HTN and more severe renal dysfunction. TMAO, combined with ß 2-macroglobulin levels, may assist in diagnosing CKD in hypertensive patients. Plasma TMAO has predictive value for early kidney disease in hypertensive patients.
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Hipertensão/sangue , Metilaminas/sangue , Insuficiência Renal Crônica/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , Fatores de RiscoRESUMO
BACKGROUND: COVID-19 is highly contagious, and the crude mortality rate could reach 49% in critical patients. Inflammation concerns on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. METHODS: In this cross-sectional study, 100 patients were included and divided into mild, severe or critical groups according to disease condition. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. RESULTS: Significantly, disease severity was associated with age (R = -0.564, P < 0.001), interleukin-2 receptor (IL2R) (R = -0.534, P < 0.001), interleukin-6 (IL-6) (R = -0.535, P < 0.001), interleukin-8 (IL-8) (R = -0.308, P < 0.001), interleukin-10 (IL-10) (R = -0.422, P < 0.001), tumor necrosis factor α (TNFα) (R = -0.322, P < 0.001), C-reactive protein (CRP) (R = -0.604, P < 0.001), ferroprotein (R = -0.508, P < 0.001), procalcitonin (R = -0.650, P < 0.001), white cell counts (WBC) (R = -0.54, P < 0.001), lymphocyte counts (LC) (R = 0.56, P < 0.001), neutrophil count (NC) (R = -0.585, P < 0.001) and eosinophil counts (EC) (R = 0.299, P < 0.001). With IL2R > 793.5 U/mL or CRP > 30.7 ng/mL, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. CONCLUSIONS: Inflammation is closely related to severity of COVID-19, and IL-6 and TNFα might be promising therapeutic targets.
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COVID-19/diagnóstico , Inflamação/complicações , Adulto , Idoso , Área Sob a Curva , Proteína C-Reativa/metabolismo , COVID-19/imunologia , Estudos Transversais , Feminino , Humanos , Inflamação/imunologia , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear. METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80+ ratio and CD11c+ ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking. RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80+CD11c+ M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4. CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.
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Berberina/farmacologia , Macrófagos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Berberina/química , Polaridade Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/química , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/química , Fator 88 de Diferenciação Mieloide/genética , Ligação Proteica/efeitos dos fármacos , Células RAW 264.7 , Receptor 4 Toll-Like/química , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Jiao-Tai-Wan (JTW), composed of Rhizome Coptidis and Cortex Cinnamomi, is a classical traditional Chinese prescription for treating insomnia. Several in vivo studies have concluded that JTW could exert its therapeutical effect in insomnia rats. However, the specific mechanism is still unclear. The present study aimed to explore the effect of JTW on sleep in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD) and to clarify its possible mechanism. METHODS: JTW was prepared and the main components contained in the granules were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The Male Sprague-Dawley (SD) rats underwent 4 h PSD by environmental noise and the treatment with low and high doses of JTW orally for 4 weeks, respectively. Then sleep structure was analyzed by electroencephalographic (EEG). Inflammation markers including high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were examined in the rat plasma. Meanwhile, metabolic parameters as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (HOMA-IR) were measured. The expressions of clock gene cryptochromes (Cry1 and Cry2) and inflammation gene nuclear factor-κB (NF-κB) in peripheral blood monocyte cells (PBMC) were also determined. RESULTS: The result showed that the administration of JTW significantly increased total sleep time and total slow wave sleep (SWS) time in OR rats with PSD. Furthermore, the treatment with JTW reversed the increase in the markers of systemic inflammation and insulin resistance caused by sleep loss. These changes were also associated with the up-regulation of Cry1 mRNA and Cry 2 mRNA and the down-regulation of NF-κB mRNA expression in PBMC. CONCLUSIONS: This study suggests that JTW has the beneficial effects of improving sleep, inflammation and insulin sensitivity. The mechanism appears to be related to the modulation of circadian clock and inflammation genes expressions in PBMC.
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Medicamentos de Ervas Chinesas/administração & dosagem , Resistência à Insulina , Obesidade/tratamento farmacológico , Privação do Sono/tratamento farmacológico , Animais , Proteína C-Reativa/metabolismo , Humanos , Interleucina-6/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , NF-kappa B/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Ratos , Ratos Sprague-Dawley , Sono/efeitos dos fármacos , Privação do Sono/metabolismo , Privação do Sono/fisiopatologiaRESUMO
Diabetic kidney disease (DKD) is a chronic renal microvascular complication associated with abnormal glucose metabolism, which is an important cause of end stage renal disease. Diabetes can damage the kidney through many ways, including renal vascular, glomerular, tubular, and renal interstitial damages. Therefore, a comprehensive treatment process must be taken for the treatment of DKD, and the selection of appropriate drugs has important significance in the treatment of DKD. Berberine has significant curative effect in the treatment of DKD, and the mechanism is related to the reduction of blood sugar, improvement of renal hemodynamics abnormality, regulation of blood lipid profile and the attenuation of systemic and local inflammation.
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Berberina/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Glicemia , Humanos , Rim/efeitos dos fármacos , Falência Renal CrônicaRESUMO
Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities.
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Movimento Celular , Estimulação Elétrica/métodos , Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Nervo Isquiático/metabolismo , Animais , Axônios/metabolismo , Forma Celular , Sobrevivência Celular , Condutividade Elétrica , Estimulação Elétrica/instrumentação , Desenho de Equipamento , Feminino , Fenótipo , Polietilenotereftalatos/química , Ratos Sprague-Dawley , Nervo Isquiático/citologia , Têxteis , Fatores de Tempo , Técnicas de Cultura de TecidosRESUMO
Diabetes is seriously hazards to human health and its pathogeneses are not clear. Recent studies show that the imbalance of intestinal flora and the development of diabetes are closely related. Appropriate bacteria can improve blood sugar disorder. Treating diabetes from the theory of Pi-Wei is effective. Regulating intestinal flora has become a new pathway for treating diabetes from the theory of Pi-Wei. On the basis of intestinal flora, authors discussed the treatment of diabetes from Pi and Wei.
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Diabetes Mellitus/microbiologia , Diabetes Mellitus/terapia , Microbioma Gastrointestinal , Bactérias , Glicemia/análise , HumanosRESUMO
Accumulating evidence indicated that leukocyte telomere length (LTL) was related to sarcopenia. However, it is still not clear whether the association of changes in LTL with sarcopenia is likely to be causal, or could be explained by reverse causality. Thus, we carried on bidirectional Mendelian randomization (MR) and multivariable MR analyses to identify the causal relationship between LTL and sarcopenia-related traits. Summary-level data and independent variants used as instruments came from large genome-wide association studies of LTL (472,174 participants), appendicular lean mass (450,243 participants), low grip strength (256,523 participants), and walking pace (450,967 participants). We identified suggestive association of longer LTL with larger appendicular lean mass [odds ratio (OR) = 1.053; 95% confidence interval (CI), 1.009-1.099; P = 0.018], and causal association of longer LTL with a lower risk of low grip strength (OR = 0.915; 95% CI, 0.860-0.974; P = 0.005). In the reverse MR analysis, we also observed a positive causal association between walking pace and LTL (OR = 1.252; 95% CI, 1.121-1.397; P < 0.001). Similar results can be repeated in sensitivity analyses. While in the multivariable MR analysis, the estimate of the impact of walking pace on LTL underwent a transformation after adjusting for T2DM (OR = 1.141; 95%CI: 0.989-1.317; P = 0.070). The current MR analysis supported a causal relationship between shorter telomere length and both low muscle mass and strength. Additionally, walking pace may affect LTL through T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Sarcopenia , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Sarcopenia/genética , Leucócitos , Telômero/genéticaRESUMO
Background: Accumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the associations of brain structural alterations with migraine are likely to be causal, or could be explained by reverse causality confounding. Methods: We carried on a bidirectional Mendelian randomization analysis in order to identify the causal relationship between brain structures and migraine risk. Summary-level data and independent variants used as instruments came from large genome-wide association studies of total surface area and average thickness of cortex (33,992 participants), gray matter volume (8,428 participants), white matter hyperintensities (50,970 participants), hippocampal volume (33,536 participants), and migraine (102,084 cases and 771,257 controls). Results: We identified suggestive associations of the decreased surface area (OR = 0.85; 95% CI, 0.75-0.96; P = 0.007), and decreased hippocampal volume (OR = 0.74; 95% CI, 0.55-1.00; P = 0.047) with higher migraine risk. We did not find any significant association of gray matter volume, cortical thickness, or white matter hyperintensities with migraine. No evidence supporting the significant association was found in the reverse MR analysis. Conclusion: We provided suggestive evidence that surface area and hippocampal volume are causally associated with migraine risk.
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BACKGROUND: Observational studies have suggested that depression is associated with sarcopenia. However, the causal relationship between depression and sarcopenia remains unclear. AIM: To investigate the causal relationship between depression and sarcopenia. METHODS: We performed a Mendelian randomization (MR) analysis to identify the bidirectional relationship between depression and sarcopenia-related traits. Summary-level data and independent variants used as instrumental variables came from large genome-wide association studies of depression (414055 cases and 892299 controls), of appendicular lean mass (ALM, 450243 participants), and of hand grip strength (exposure: 360000 participants; outcome: 334925 participants). RESULTS: We identified a negative association of depression with lower ALM [odds ratio (OR): 0.932, 95% confidence interval (95%CI): 0.889-0.979, P = 0.005]. In the reverse MR analysis, we also observed an inverse association of hand grip strength with depression (OR: 0.200, 95%CI: 0.108-0.370, P < 0.001). Similar results were obtained in sensitivity analyses. CONCLUSION: Depression was causally related to decreased muscle mass, and declined muscle strength might lead to a higher risk of depression.
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AIM: MicroRNA-497 (miR-497) directly targets fibroblast growth factor 23 (FGF23) to participate in the pathology of acute coronary syndrome (ACS) by regulating atherosclerosis, inflammatory response, lipid metabolism, etc. This study intended to investigate the dysregulation of the miR-497/FGF23 axis, and its association with the major adverse cardiovascular event (MACE) in female premature ACS. METHODS: MiR-497 and FGF23 from plasma samples were detected by RT-qPCR and ELISA in 979 newly diagnosed female premature ACS patients and 100 healthy controls (HCs). MACE was recorded during follow-up (median: 27.0, range: 1.0-54.0 months) in female premature ACS patients. RESULTS: MiR-497/FGF23 axis was reduced in female premature ACS patients versus HCs [median (interquartile range): 0.7 (0.1-1.2) versus 1.9 (1.1-3.4)] (P < 0.001). Meanwhile, miR-497 negatively correlated with FGF23 in femal e premature ACS patients (P < 0.001), but not in HCs (P = 0.157). In female premature ACS patients, the miR-497/FGF23 axis was negatively associated with serum creatinine (P < 0.001), serum uric acid (P = 0.003), high-sensitivity C-reactive protein (P < 0.001), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.003). The 1-year, 2-year, 3-year, and 4-year accumulating MACE rate was 2.9%, 8.6%, 16.7%, and 26.0%, respectively. Interestingly, a high level of miR-497/FGF23 axis predicted decreased accumulating MACE risk (P < 0.001). After adjustment by multivariate Cox's regression analysis, the high miR-497/FGF23 axis (hazard ratio (HR) = 0.005, P = 0.001) independently correlated with reduced accumulating MACE risk. CONCLUSION: The plasma miR-497/FGF23 axis represents favorable kidney function, decreased inflammation, and reduced lipid level; meanwhile, this axis possesses prognostic value in predicting decreased accumulating MACE risk in female premature ACS patients.
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Síndrome Coronariana Aguda , Fator de Crescimento de Fibroblastos 23 , MicroRNAs , Feminino , Humanos , Síndrome Coronariana Aguda/genética , Colesterol , Prognóstico , Fatores de Risco , Ácido ÚricoRESUMO
Radioresistance restrains the therapeutic effect of nasopharyngeal carcinoma (NPC). Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 sensitized NPC cells to radiation and to explore the possible mechanisms. Our results revealed that Rg3 increased radiosensitivity in both HNE1 and CNE2 cell lines. Radiation induced epithelial mesenchymal transition (EMT) in NPC cells and Rg3 blocked this effect. In addition, Rg3 attenuated radiation-induced epidermal growth factor receptor (EGFR) nuclear transport and DNA-dependent protein kinase expression. What's more, Rg3 significantly accelerated the apoptosis rates in irradiated NPC cells. In summary, our data suggested that Rg3 sensitized NPC cells to radiation and suppressed radiation-induced EMT. This effect is mediated through restrained EGFR nuclear translocation and increased cell apoptosis. Thus, Rg3 may be a potential radiation sensitizing agent for NPC.
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Transição Epitelial-Mesenquimal , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Linhagem Celular Tumoral , Tolerância a Radiação , Neoplasias Nasofaríngeas/radioterapia , Receptores ErbBRESUMO
Purpose: So far, ST-segment elevation myocardial infarction (STEMI) is still the main cause of morbidity and mortality of cardiovascular diseases worldwide. Recent studies showed that pentraxin-3 (PTX3) was related to the early diagnosis and prognosis of coronary heart disease. This study aimed to investigate the dynamical change of PTX3 after primary percutaneous coronary intervention (pPCI) in STEMI patients and its prognostic value. Patients and methods: In this prospective cohort study, a total of 350 patients were enrolled. The plasma level of PTX3 was measured at admission, 24-hour and 5-day after pPCI. The primary endpoint was the incidence of major adverse cardiac cerebral events (MACCEs) during 1-year follow-up. Results: Compared with the admission, PTX3 levels were significantly increased at 24 hours, and decreased at 5 days after pPCI in the whole cohort. PTX3 levels at these three time points were not significantly different between the patients with and without MACCEs. Notably, the change in PTX3 from admission to post-pPCI 24-hour (ΔPTX3) was higher in patients with MACCEs (112.83 vs 17.94 ng/dl, P = 0.001). The ROC curves showed that the cut-off value was 29.22 ng/dl and the area under curves was 0.622 (95% CI: 0.554-0.690, p = 0.001). Multivariable cox regression models revealed that the high ΔPTX3 group was an independent predictor of MACCEs (adjusted HR = 2.010, 95% CI = 1.280-3.186, p = 0.003). The higher ΔPTX3 group had significantly higher incidences of revascularization (HR = 2.094, 95% CI: 1.056-4.150, p = 0.034) and composite MACCEs (HR = 2.219, 95% CI: 1.425-3.454, p < 0.001). However, the change of PTX3 level from admission to post-pPCI 5-day had no independently predictive value. Conclusion: The higher increase of PTX3 level 24-hour after pPCI appeared to have a potential value in independently predicting the incidence of 1-year MACCEs in STEMI patients, especially for coronary revascularization.
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Solid-state zinc-ion capacitors are emerging as promising candidates for large-scale energy storage owing to improved safety, mechanical and thermal stability and easy-to-direct stacking. Hydrogel electrolytes are appealing solid-state electrolytes because of eco-friendliness, high conductivity and intrinsic flexibility. However, the electrolyte/electrode interfacial contact and anti-freezing properties of current hydrogel electrolytes are still challenging for practical applications of zinc-ion capacitors. Here, we report a class of hydrogel electrolytes that couple high interfacial adhesion and anti-freezing performance. The synergy of tough hydrogel matrix and chemical anchorage enables a well-adhered interface between hydrogel electrolyte and electrode. Meanwhile, the cooperative solvation of ZnCl2 and LiCl hybrid salts renders the hydrogel electrolyte high ionic conductivity and mechanical elasticity simultaneously at low temperatures. More significantly, the Zn||carbon nanotubes hybrid capacitor based on this hydrogel electrolyte exhibits low-temperature capacitive performance, delivering high-energy density of 39 Wh kg-1 at -60 °C with capacity retention of 98.7% over 10,000 cycles. With the benefits of the well-adhered electrolyte/electrode interface and the anti-freezing hydrogel electrolyte, the Zn/Li hybrid capacitor is able to accommodate dynamic deformations and function well under 1000 tension cycles even at -60 °C. This work provides a powerful strategy for enabling stable operation of low-temperature zinc-ion capacitors.
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Type 2 diabetes mellitus (T2DM) and its complications are major public health problems that seriously affect the quality of human life. The modification of intestinal microbiota has been widely recognized for the management of diabetes. The relationship between T2DM, intestinal microbiota, and active ingredient berberine (BBR) in intestinal microbiota was reviewed in this paper. First of all, the richness and functional changes of intestinal microbiota disrupt the intestinal environment through the destruction of the intestinal barrier and fermentation/degradation of pathogenic/protective metabolites, targeting the liver, pancreas, visceral adipose tissue (VAT), etc., to affect intestinal health, blood glucose, and lipids, insulin resistance and inflammation. Then, we focus on BBR, which protects the composition of intestinal microbiota, the changes of intestinal metabolites, and immune regulation disorder of the intestinal environment as the therapeutic mechanism as well as its current clinical trials. Further research can analyze the mechanism network of BBR to exert its therapeutic effect according to its multi-target compound action, to provide a theoretical basis for the use of different phytochemical components alone or in combination to prevent and treat T2DM or other metabolic diseases by regulating intestinal microbiota.