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Simultaneously achieving high mass loading and superior rate capability in electrodes is challenging due to their often mutually constrained nature, especially for pseudocapacitors for high-power density applications. Here, we report a robust porous polyaniline hydrogel (PPH) prepared using a facile ice-templated in situ polymerization approach. Owing to the conductive, robust, and porous nanostructures suitable for ultrafast electron and ion transport, the self-supporting pure polyaniline hydrogel electrode exhibits superior areal capacitance without sacrificing rate capability and gravimetric capacitance at an ultrahigh mass loading and notable current density. It achieves a high areal capacitance (15.2 F·cm-2 at 500 mA·cm-2) and excellent rate capability (~92.7% retention from 20 to 500 mA·cm-2) with an ultrahigh mass loading of 43.2 mg cm-2. Our polyaniline hydrogel highlights the potential of designing porous nanostructures to boost the performance of electrode materials and inspires the development of other ultrafast pseudocapacitive electrodes with ultrahigh loadings and fast charge/discharge capabilities.
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Objective: The purpose of this study is to conduct a systematic review to assess the effects of different forms of resistance exercises (resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises) on physical fitness, quality of life (QOL), and fatigue of patients with cancer. Methods: We conducted a systematic review using the Cochrane Handbook for Systematic Reviews of Interventions guidelines. We searched PubMed, Web of Science, and Scopus databases for the studies from the establishment of the database to September 2023, including randomized controlled trials and clinical trials that evaluated the effects of different resistance exercise on physical fitness, QOL, and fatigue in all patients with cancer. Two reviewers independently assessed the quality of all the included studies using the Cochrane Handbook for Systematic Reviews of Interventions and MINORS scale. We divided the intervention into three types: resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises. Results: In total, 48 studies (3,843 participants) met the inclusion criteria. The three exercise intervention forms have significant effects on physical fitness and QOL, but the improvement effect on fatigue is not clear. A total of 34 studies reported significant and beneficial effects of resistance exercise on physical fitness across all types of cancer. There were 28 studies that reported significant or borderline improvement effects of resistance on QOL, and only 10 studies reported significant effects of resistance exercise interventions on fatigue improvement in patients with cancer. Conclusions: Resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises all have a positive effect on improving fitness and QOL in patients with cancer. Resistance exercise has an advantage in improving muscle strength, while combined resistance exercise has an advantage in improving QOL; however, there are no consistent findings in improving fatigue, although low-intensity resistance exercise is effective. Systematic review registration: www.inplasy.com, identifier INPLASY2023110034.
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Radioiodine (mainly 129I and 131I) is known to be dangerous nuclear waste due to its high toxicity, fast mobility and long radioactive half-life. As an emerging class of novel porous organic polymers, covalent organic frameworks (COFs) have demonstrated tremendous application potential in the field of radioactive iodine capture because of their high specific surface area and tunable pore structure. Herein, three π-conjugated pyrene-based COFs, namely PyTTA-BPDA-COF, PyTTA-BPY-COF, and PyTTA-BT-COF, have been successfully prepared and used as highly efficient adsorbents for iodine capture. The experimental results show that the three COFs displayed excellent adsorption performance, with adsorption capacity of 5.03, 4.46, and 3.97 g g-1 for PyTTA-BPDA-COF, PyTTA-BPY-COF, and PyTTA-BT-COF, respectively. Additionally, the release rate of iodine-loaded COFs in methanol solution and recyclability were also impressive, demonstrating their potential for practical applications. The mechanism investigation reveals that both imine linkage and π-conjugated structure of the COFs may contribute to their high iodine adsorption capability. This work is instructive as a guide for designing and synthesizing COFs as a solid-phase adsorbent for iodine uptake.
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Unlike chemosynthetic drugs designed for specific molecular and disease targets, active small-molecule natural products typically have a wide range of bioactivities and multiple targets, necessitating extensive screening and development. To address this issue, we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action. As a proof-of-concept, we investigated the behavior of mussel oligosaccharide (MOS-1) by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells. We recorded the entire dynamic process of the localization of fluorescein isothiocyanate (FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell. Remarkably, lysosomes containing FITC-MOS-1 actively recruited lipid droplets, leading to fusion events and increased cellular lipid consumption. These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases. Furthermore, in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E (ApoE) -/- mice, MOS-1 significantly promoted triglyceride degradation, reduced lipid droplet accumulation, lowered serum triglyceride levels, and mitigated liver damage and steatosis. Overall, our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase, as this methodology contributes to the rapid identification of drug indications. Collectively, this methodology is significant for the screening and development of selective small-molecule drugs, and is expected to expedite the identification of candidate molecules with medicinal effects.
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A novel polysaccharide, GPH1, was extracted and isolated from ginseng. Structural analysis of GPH1 revealed a molecular weight of 7.321 × 105 Da and the presence of glucose and galactose components in a 30.2: 1 molar ratio. Results of methylation and NMR analyses indicated the GPH1 backbone consisted of â1)-α-Glc-(3â and â1)-α-Glc-(6â. The anti-obesity activity of GPH1 was assessed by HFD-induced obesity mouse model. GPH1 was found to significantly reduced body weight, alleviated liver lipid accumulation and inflammatory damage. Meanwhile, GPH1 treatment increased the expression of tight junction proteins, including zonula occludens-1 (ZO-1) and claudin-1, while also regulating the intestinal microbiota of obese mice by promoting proliferation of beneficial bacteria with known anti-obesity effects, including s_Akkermansia muciniphila, s_Lactobacillus intestinalis, s_Lactobacillus reuteri, s_Streptococcus hyointestinalis, and s_Lactococcus garvieae. Our findings demonstrated that GPH1 is a practical natural dietary supplement with potential therapeutic effects on obesity.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Obesidade , Panax , Polissacarídeos , Animais , Panax/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Dieta Hiperlipídica/efeitos adversos , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos Obesos , Masculino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.
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Eritrócitos , Glicólise , Peróxido de Hidrogênio , Estresse Oxidativo , Panax , Ratos Sprague-Dawley , Saponinas , Tirosina , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Saponinas/farmacologia , Animais , Glicólise/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/farmacologia , Tirosina/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Hemólise/efeitos dos fármacos , Antioxidantes/farmacologia , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Apoptose/efeitos dos fármacosRESUMO
Necrotizing enterocolitis (NEC) is one of the most common and serious intestinal illnesses in newborns and seriously affects their long-term prognosis and survival. Butyrate is a short-chain fatty acid that can relieve intestinal inflammation, but its mechanism of action is unclear. Results from an in vivo neonatal rat model has shown that butyrate caused an improved recovery from NEC. These protective effects were associated with the metabolite of hesperetin, as determined by metabolomics and molecular biological analysis. Furthermore, transcriptomics combined with inhibitor assays were used to investigate the mechanism of action of hesperetin in an in vitro NEC model (IEC-6 cells exposed to LPS) to further investigate the mechanism by which butyrate attenuates NEC. The transcriptomics analysis showed that the PI3K-Akt signaling pathway was involved in the anti-NEC effect of hesperitin. Subsequently, the results using an inhibitor of PI3K (LY294002) indicated that the suppression could be explained by the hesperetin-induced expression of tight junction (TJ) proteins by potentially blocking the PI3K-Akt signaling pathway. In summary, the present study demonstrated that butyrate could improve recovery from NEC with a hesperetin metabolite, causing potential inhibition of the phosphorylation of the PI3K-Akt signaling pathway, resulting in the increased expression of TJ proteins. These findings reveal a potential new therapeutic pathway for the treatment of NEC.
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Enterocolite Necrosante , Hesperidina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Enterocolite Necrosante/tratamento farmacológico , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Hesperidina/farmacologia , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Animais Recém-Nascidos , Modelos Animais de Doenças , Butiratos/farmacologia , Linhagem CelularRESUMO
Erectile dysfunction is a complex and common complication of diabetes mellitus, which lacks an effective treatment. The repairing role of vascular endothelium is the current research hotspot of diabetic mellitus erectile dysfunction (DMED), and the activation of PI3K/AKT/eNOS pathway positively affects the repair of vascular endothelium. The herbal extract isorhamnetin has significant vasoprotective effects and has great potential in treating DMED. This study aimed to clarify whether isorhamnetin has an ameliorative effect on DMED and to investigate the modulation of the PI3K/AKT/eNOS signaling pathway by isorhamnetin to discover its potential mechanism of action. In vivo experiments were performed using a streptozotocin-induced diabetic rat model, and efficacy was assessed after 4 weeks of isorhamnetin gavage administration at 10â¯mg/kg or 20â¯mg/kg. Erectile function in rats was assessed by maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), and changes in corpus cavernosum (CC) fibrosis, inflammation levels, oxidative stress levels, and apoptosis were assessed by molecular biology techniques. In vitro experiments using high glucose-induced corpus cavernosum endothelial cells were performed to further validate the anti-apoptotic effect of isorhamnetin and its regulation of the PI3K/AKT/eNOS pathway. The findings demonstrated that isorhamnetin enhanced erectile function, decreased collagen content, and increased smooth muscle content in the CC of diabetic rats. In addition, isorhamnetin decreased the serum levels of pro-inflammatory factors IL-6, TNF-α, and IL-1ß, increased the levels of anti-inflammatory factors IL-10 and IL-4, increased the activities of SOD, GPx, and CAT as well as the levels of NO, and decreased the levels of MDA in corpus cavernosum tissues. Isorhamnetin also increased the content of CD31 in CC tissues of diabetic rats, activated the PI3K/AKT/eNOS signaling pathway, and inhibited apoptosis. In conclusion, isorhamnetin exerts a protective effect on erectile function in diabetic rats by reducing the inflammatory response, attenuating the level of oxidative stress and CC fibrosis, improving the endothelial function and inhibiting apoptosis. The mechanism underlying these effects may be linked to the activation of the PI3K/AKT/eNOS pathway.
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Disfunção Erétil , Estresse Oxidativo , Quercetina , Transdução de Sinais , Animais , Masculino , Ratos , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Quercetina/análogos & derivados , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.
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The effective capture and recovery of radioiodine species associated with nuclear fuel reprocessing is of significant importance in nuclear power plants. Porous materials have been proven to be one of the most effective adsorbents for the capture of radioiodine. In this work, we design and synthesize a series of conjugated microporous polymers (CMPs), namely, TPDA-TFPB CMP, TPDA-TATBA CMP, and TPDA-TECHO CMP, which are constructed based on a planar rectangular 4-connected organic monomer and three triangular 3-connected organic monomers, respectively. The resultant CMPs are characterized using various characterization techniques and used as effective adsorbents for iodine capture. Our experiments indicated that the CMPs exhibit excellent iodine adsorption capacities as high as 6.48, 6.25, and 6.37 g g-1 at 348 K and ambient pressure. The adsorption mechanism was further investigated and the strong chemical adsorption between the iodine and the imine/tertiary ammonia of the CMPs, 3D network structure with accessible hierarchical pores, uniform micromorphology, wide π-conjugated structure, and high-density Lewis-base sites synergistically contribute to their excellent iodine adsorption performance. Moreover, the CMPs demonstrated good recyclability. This work provides guidance for the construction of novel iodine adsorbent materials with high efficiency in the nuclear power field.
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Aï¬atoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aï¬atoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3â¯mg/kg body b.w.) and AFM1(3.0â¯mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.
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Aflatoxina B1 , Aflatoxina M1 , Proteômica , Aflatoxina M1/toxicidade , Aflatoxina B1/toxicidade , Animais , Camundongos , Células CACO-2 , Humanos , Masculino , Intestinos/efeitos dos fármacos , Intestinos/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismoRESUMO
With the expansion of the application of high-sensitivity Surface-enhanced Raman scattering (SERS) technique, micro SERS-active substrates with rich optical properties and high-level functions are desired. In this study, silver nanorings with nanoscale surface roughness were fabricated as a new type of enclosed quasi-2D micro-SERS-active substrate. Highly-crystalline spherical and hemispherical silver nanoprotrusions were densely and uniformly distributed over the entire surface of the nanorings. The SERS signals were significantly enhanced on the roughened silver nanorings which were mainly derived from the maximal localized surface plasmon resonance (LSPR) points at the junctions between adjacent coupled nanoprotrusions on the roughened nanorings. The mapping image shows a uniform and intense LSPR enhancement over the nanorings, owing to the uniform and dense distribution of silver nanoprotrusions and the resulting uniform distribution of maximal LSPR points on the roughened nanorings. The dark-field spectra further indicated that the single roughened silver nanoring had significant LSPR enhancement, a wide LSPR frequency-range response, and adaptability for SERS enhancement. Notably, both the measured and simulated results demonstrate that the maximal LSPR enhancement at the junctions between the nanoprotrusions, which are distributed on the inner surface of the silver nanoring, is higher than that on the outer surface because of the plasmon-focusing effect of the enclosed silver nanoring, which leads to the lateral asymmetrical distribution of LSPR intensity, indicating more LSPR and SERS features. These results indicate that single roughened silver nanorings exhibit excellent performance as a new type of enclosed quasi-2D silver nanoring micro-SERS-active substrate, microzone LSPR catalysis, and micro/nanodevices.
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Simultaneous imaging of nitric oxide (NO) and its proximal proteins should facilitate the deconvolution of NO-protein interactions. While immunostaining is a primary assay to localize proteins in non-genetically manipulated samples, NO imaging probes with immunostaining-compatible signals remain unexplored. Herein, probe NOP-1 was developed with an NO-triggered proximal protein labeling capacity and fluorogenic signals. The trick is to fuse the native chemical ligation of acyl benzotriazole with the protein-conjugation-induced fluorogenic response of Si-rhodamine fluorophore. NOP-1 predominantly existed in the non-fluorescent spirocyclic form. Yet, its acyl o-phenylenediamine moiety was readily activated by NO into acyl benzotriazole to conjugate proximal proteins, providing a fluorogenic response and translating the transient cellular NO signal into a permanent stain compatible with immunostaining. NOP-1 was utilized to investigate NO signaling in hypoglycemia-induced neurological injury, providing direct evidence of NO-induced apoptosis during hypoglycemia. Mechanistically, multiplex imaging revealed the overlap of cellular NOP-1 fluorescence with immunofluorescence for α-tubulin and NO2-Tyr. Importantly, α-tubulin was resolved from NOP-1 labeled proteins. These results suggest that NO played a role in hypoglycemia-induced apoptosis, at least in part, through nitrating α-tubulin. This study fills a crucial gap in current imaging probes, providing a valuable tool for unraveling the complexities of NO signaling in biological processes.
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Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.
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Doenças Autoimunes , Exossomos , Exossomos/imunologia , Humanos , Doenças Autoimunes/terapia , Doenças Autoimunes/imunologia , Animais , Nanopartículas/químicaRESUMO
BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.
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LDL-Colesterol , Colesterol , Lipoproteína(a) , Triglicerídeos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Triglicerídeos/sangue , Fatores de Risco , LDL-Colesterol/sangue , Lipoproteína(a)/sangue , Colesterol/sangue , Hipolipemiantes/uso terapêutico , Apolipoproteínas B/sangue , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , Biomarcadores/sangueRESUMO
BACKGROUND: In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of the testis-specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain high blood pressure during hypertension. METHODS: Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral microinjection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured. RESULTS: TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1ß, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the BP in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1ß and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs. CONCLUSION: JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high BP in hypertensive rats, making it a potential therapeutic target for hypertension.
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Pressão Sanguínea , Hipertensão , Janus Quinase 2 , Núcleo Hipotalâmico Paraventricular , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/enzimologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Norepinefrina/metabolismo , Ratos , Tirfostinas/farmacologia , FosforilaçãoRESUMO
Inflammatory bowel disease (IBD) comprises a group of highly prevalent and chronic inflammatory intestinal tract diseases caused by multiple factors. Despite extensive research into the causes of the disease, IBD's pathogenic mechanisms remain unclear. Moreover, side effects of current IBD therapies restrict their long-term clinical use. In contrast, natural polysaccharides exert beneficial anti-IBD effects and offer advantages over current anti-IBD drugs, including enhanced safety and straightforward isolation from abundant and reliable sources, and thus may serve as components of functional foods and health products for use in IBD prevention and treatment. However, few reviews have explored natural polysaccharides with anti-IBD activities or the relationship between polysaccharide conformation and anti-IBD biological activity. Therefore, this review aims to summarize anti-IBD activities and potential clinical applications of polysaccharides isolated from plant, animal, microorganismal, and algal sources, while also exploring the relationship between polysaccharide conformation and anti-IBD bioactivity for the first time. Furthermore, potential mechanisms underlying polysaccharide anti-IBD effects are summarized, including intestinal microbiota modulation, intestinal inflammation alleviation, and intestinal barrier protection from IBD-induced damage. Ultimately, this review provides a theoretical foundation and valuable insights to guide the development of natural polysaccharide-containing functional foods and nutraceuticals for use as dietary IBD therapies.
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Polissacarídeos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Humanos , Animais , Relação Estrutura-Atividade , Microbioma Gastrointestinal/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Alimento FuncionalRESUMO
Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.
Assuntos
Lesão Pulmonar Aguda , Plantas Medicinais , Pneumonia Viral , Pneumonia , Camundongos , Animais , Macrófagos Alveolares/metabolismo , Pulmão/metabolismo , Pneumonia Viral/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Mitocôndrias/patologia , Ácido gama-Aminobutírico/metabolismo , Pneumonia/metabolismoRESUMO
Objective: This study aimed to compare the effects of two concurrent training (CT) protocols on the physical fitness of middle school students. Method: A 12-week quasi-experimental pre-test/post-test study was conducted with 157 middle school students (age = 12.48 ± 0.34, n = 90 females) divided into three groups: CT group A (CT-0h) received combined resistance training (RT) and aerobic training (AT) in each physical education session, CT group B (CT-48h) received RT and AT across two separate physical education classes 48 h apart, and a control group (Con) received no training. Training occurred twice a week. Test indicators included cardiorespiratory fitness (CRF) measured by estimated VO2max and 20 m shuttle run (laps), as well as muscle strength assessed through long jump, vertical jump, and handgrip strength. Results: The intervention groups exhibited significant increases in estimated VO2max and muscle strength compared to their baseline values (p < 0.05). Both CT-0h and CT-48h groups demonstrated significant improvements in 20 m shuttle run (laps) (mean difference: 8.88 laps, p < 0.01; mean difference: 4.81 laps, p < 0.01, respectively), standing long jump (mean difference: 6.20 cm, p < 0.01; mean difference: 3.68 cm, p < 0.01, respectively), vertical jump (mean difference: 4.95 cm, p < 0.01; mean difference: 4.04 cm, p < 0.01, respectively), and handgrip strength (mean difference: 11.17 kg, p < 0.01; mean difference: 6.99 kg, p < 0.01, respectively). CT-0h group exhibited significantly increased estimated VO2max (mean difference: 1.47 ml/kg/min, p < 0.01) compared to the CT-48h group. Conclusion: Both CT programs effectively improved adolescents' physical fitness indicators. However, the program that integrated RT and AT within the same physical education class demonstrated superior enhancement in adolescents' CRF.
Assuntos
Aptidão Física , Treinamento Resistido , Humanos , Feminino , Masculino , Treinamento Resistido/métodos , Aptidão Física/fisiologia , Criança , Adolescente , Força Muscular/fisiologia , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Estudantes/estatística & dados numéricos , Educação Física e Treinamento/métodosRESUMO
The design and synthesis of organic photocatalysts remain a great challenge due to their strict structural constraints. However, this could be mitigated by achieving structural flexibility by constructing permanent porosity into the materials. Conjugated microporous polymers (CMPs) are an emerging class of porous materials with an amorphous, three-dimensional network structure, which makes it possible to integrate the elaborate functional groups to enhance photocatalytic performance. Here, we report the synthesis of a novel CMP, named TAPFc-TFPPy-CMP, constructed by 1,1'3,3'-tetra(4-aminophenyl)ferrocene (TAPFc) and 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) monomers. The integration of the p-type dopant 7,7,8,8-tetracyanoquinodimethane (TCNQ) into the TAPFc-TFPPy-CMP improved the light adsorption performance, leading to a decrease in the optical bandgap from 2.00 to 1.43 eV. The doped CMP (TCNQ@TAPFc-TFPPy-CMP) exhibited promising catalytic activity in photocatalytic CO2 reduction under visible light, yielding 546.8 µmol g-1 h-1 of CO with a selectivity of 96% and 5.2 µmol g-1 h-1 of CH4. This represented an 80% increase in the CO yield compared to the maternal TAPFc-TFPPy-CMP. The steady-state photoluminescence (PL) and fluorescence lifetime (FL) measurements reveal faster carrier separation and transport after the doping. This study provides guidance for the development of organic photocatalysts for the utilization of renewable energy.