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Background: The primary constituent of ginseng, known as ginsenosides (GS), has been scientifically demonstrated to possess anti-fatigue, anti-hypoxia, anti-inflammatory, and antioxidant properties. However, the effect and mechanisms of GS on tissue injury induced by high-altitude hypoxia still remain unclear. Aim of the study: This study aims to investigate the protective effect of GS on a high-altitude hypoxia model and explore its mechanism. Materials and methods: Sprague-Dawley rats were placed in a high-altitude simulation chamber for 48 h (equivalent to an altitude of 6,000 m) to establish a high-altitude hypoxia model. We assessed the anti-hypoxic efficacy of GS through blood gas analysis, complete blood count, and hemorheology analysis. We used H&E and hypoxia probe assays to evaluate the protective effect of GS on organ ischemia-induced injury. Further, we used ELISA and qPCR analysis to detect the levels of inflammatory factors and oxidative stress markers. Immunohistochemistry and immunofluorescence staining were performed to determinate protein expression of hypoxia inducible factor 1-alpha (HIF-1α), erythropoietin (EPO), and prolyl hydroxylase 2 (PHD2). Results: In the survival experiment of anoxic mice, 100 mg/kg of GS had the best anti-anoxic effect. GS slowed down the weight loss rate of rats in hypoxic environment. In the fluorescence detection of hypoxia, GS reduced the fluorescence signal value of lung and kidney tissue and alleviated the hypoxia state of tissue. Meanwhile GS improved blood biochemical and hematological parameters. We also observed that GS treatment significantly decreased oxidative stress damage in lung and kidney tissues. Further, the levels of inflammatory factors, IL-1ß, IL-6, and TNF-α were reduced by GS. Finally, GS regulated the PHD2/HIF-1α/EPO signaling pathway to improve blood viscosity and tissue hyperemia damage. Conclusion: GS could alleviate high-altitude induced lung and kidney damage by reducing the level of inflammation and oxidative stress, improving blood circulation through the PHD2/HIF-1α/EPO pathway.
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The separation and utilization of cellulose, hemicellulose, and lignin in lignocellulosic biorefineries present significant challenges. This study proposes a pretreatment method for biomass refining by combining acid and kraft pulping. Firstly, the biomass was pretreated by malic acid, resulting in the isolation of xylo-oligosaccharides (XOS) with a yield of 86.26 % with optimized conditions of 180 °C, 1 wt% concentration, 40 min. Secondly, a mixture of 12.98 wt% NaOH and 1.043 wt% Na2S is employed to achieve lignin removal efficiency up to 63.42 %. Physical refinement techniques are then applied to enhance the enzyme digestion efficiency of cellulose, resulting in an increase from 55.03 % to 91.4 % for efficient cellulose conversion. The reacted samples exhibit a lignin composition rich in ß-O-4 ether bonds, facilitating their high-value utilization. The results indicated that the combined pretreatment approach demonstrates high efficiency in separating cellulose, hemicellulose, and lignin while obtaining XOS, highly active lignin, and enzyme-digested substrates.
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Exocyst, a protein complex, plays a crucial role in various cellular functions, including cell polarization, migration, invasion, cytokinesis, and autophagy. Sec3, known as Exoc1, is a key subunit of the Exocyst complex and can be involved in cell survival and apoptosis. In this study, two subtypes of Sec3 were isolated from Epinephelus coioides, an important marine fish in China. The role of E. coioides Sec3 was explored during Singapore grouper iridovirus (SGIV) infection, an important pathogen of marine fish which could induce 90 % mortality. E. coioides Sec3 sequences showed a high similarity with that from other species, indicating the presence of a conserved Sec3 superfamily domain. E. coioides Sec3 mRNA could be detected in all examined tissues, albeit at varying expression levels. SGIV infection could upregulate E. coioides Sec3 mRNA. Upregulated Sec3 significantly promoted SGIV-induced CPE, and the expressions of viral key genes. E. coioides Sec3 could inhibit the activation of NF-κB and AP-1, as well as SGIV-induced cell apoptosis. The results illustrated that E. coioides Sec3 promotes SGIV infection by regulating the innate immune response.
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Bass , Infecções por Vírus de DNA , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Filogenia , Ranavirus , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Imunidade Inata/genética , Bass/imunologia , Ranavirus/fisiologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Regulação da Expressão Gênica/imunologia , Alinhamento de Sequência/veterinária , Sequência de Aminoácidos , Perfilação da Expressão Gênica/veterináriaRESUMO
Soluble suppression of tumorigenicity-2 (sST-2), a marker of myocardial fibrosis and remodeling, has been related to the development of atrial fibrillation (AF). The aim of this meta-analysis was to evaluate the relationship between baseline serum sST-2 levels and the risk of AF recurrence after ablation. Relevant observational studies were retrieved from PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, accounting for between-study heterogeneity. Fourteen prospective cohorts were included. Pooled results showed higher sST-2 levels before ablation in patients with AF recurrence compared to those without AF recurrence (standardized mean difference = 1.15, 95% confidence interval [CI] = 0.67 to 1.63, P < 0.001; I2 = 92%). Meta-regression analysis suggested that the proportion of patients with paroxysmal AF (PaAF) was positively related to the difference in serum sST-2 levels between patients with and without AF recurrence (coefficient = 0.033, P < 0.001). Subgroup analysis showed a more remarkable difference in serum sST-2 levels between patients with and without AF recurrence in studies where PaAF was ≥ 60% compared to those where it was < 60% (P = 0.007). Further analyses showed that high sST-2 levels before ablation were associated with an increased risk of AF recurrence (odds ratio [OR] per 1 ng/mL increment of sST-2 =1.05, OR for high versus low sST-2 = 1.73, both P values < 0.05). In conclusion, high sST-2 baseline levels may be associated with an increased risk of AF recurrence after catheter ablation.
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BACKGROUND: The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Thereforeï¼this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY. OBJECTIVE: The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS. METHODS: In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB). RESULTS: The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1ß (IL-6, IL-10, IL-1ß) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses. CONCLUSION: In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.
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Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.
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Envelhecimento , Ginsenosídeos , Inositol , Metabolômica , Panax , Fosfatidilcolinas , Animais , Panax/química , Ginsenosídeos/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Fosfatidilcolinas/metabolismo , Camundongos , Masculino , Inositol/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos Endogâmicos C57BLRESUMO
CONTENT: The correlation between visceral obesity index (VAI) and diabetes and accuracy of early prediction of diabetes are still controversial. OBJECTIVE: This study aims to review the relationship between high level of VAI and diabetes, and early predictive value of diabetes. DATA SOURCES: The databases of PubMed, Cochrane, Embase, and Web of Science were searched until October 17, 2023. STUDY SELECTION: After adjusting for confounding factors, the original study on the association between VAI and diabetes was analyzed. DATA EXTRACTION: We extracted odds ratio (OR) between VAI and diabetes management after controlling for mixed factors, and the sensitivity, specificity and diagnostic four grid table for early prediction of diabetes. DATA SYNTHESIS: 53 studies, comprising 595,946 participants were included. The findings of the meta-analysis elucidated that in cohort studies, a high VAI significantly increased the risk of diabetes mellitus in males (OR = 2.83 (95% CI: 2.30-3.49)) and females (OR = 3.32 (95% CI: 2.48-4.45)). The ROC, sensitivity, and specificity of VAI for early prediction of diabetes in males were 0.64 (95% CI: 0.62-0.66), 0.57 (95% CI: 0.53-0.61), and 0.65 (95% CI: 0.61-0.69), respectively, and 0.67 (95% CI: 0.65-0.69), 0.66 (95% CI: 0.60-0.71), and 0.61 (95% CI: 0.57-0.66) in females, respectively. CONCLUSIONS: VAI is an independent predictor of the risk of diabetes, yet its predictive accuracy remains limited. In future studies, determine whether VAI can be utilized in conjunction with other related indicators to early predict the risk of diabetes, to enhance the accuracy of prediction of the risk of diabetes.
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The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng, have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri, Staphylococcus lentus, and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l-lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.
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Dieta Hiperlipídica , Fezes , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Fígado , Lisina , Obesidade , Panax , Polissacarídeos , Animais , Lisina/metabolismo , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Panax/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/química , Fezes/microbiologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BLRESUMO
Nitrate, which poses a serious threat to the drinking water supply, is one of the most prevalent anthropogenic groundwater contaminants worldwide. With the development of the chemical industry, the nitrate pollution of groundwater in the Piedmont strong runoff zone of the Hohhot Basin, which is the main groundwater extraction area, is becoming increasingly severe. The special hydrogeological and complex pollution conditions in the study area make it difficult to identify nitrate sources and transformation processes. In order to identify the results more accurately, this study combined water chemistry, multivariate statistical analysis and isotope tracer methods to determine the sources and transformation processes of nitrate in the study area. The results showed that the groundwater in the eastern part of the study area (ESA) was clearly affected by anthropogenic activities, and its nitrate was mainly from nitrification of ammonia in industrial wastewater, nitrate in industrial wastewater (the sum of the two contributions was 62.2 %), and nitrate in manure (20.5 %). The hydrogeochemical characteristics of groundwater in the western part of the study area (WSA) are the same as those of natural groundwater in the Piedmont strong-runoff zone. The nitrate in groundwater in the WSA was mainly derived from soil nitrogen (63.8 %) and ammonia fertilizer (28.8 %). Nitrification and denitrification occurred only locally in the aquifer of the study area and were more pronounced in the ESA. Meanwhile, the transformation processes of nitrate in groundwater in the ESA and WSA was significantly influenced by contamination with chlorinated hydrocarbon volatile organic compounds and hydrogeological conditions, respectively. These findings provide a scientific basis for the development of groundwater pollution prevention measures in the study area and guide the traceability of nitrate in groundwater in areas with similar hydrogeological and pollution conditions.
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Climate changes and human activities have led to a rise of frequency and intensity of the global flash droughts, resulting in severe consequences for ecosystems, agriculture, and human societies. However, research dedicated to flash droughts in the dryland of western China is relatively limited, leaving their evolutionary characteristics and development processes of these phenomena unclear. To bridge this gap, this study analyzed the spatiotemporal characteristics of flash droughts in western China from 1981 to 2020, based on the standardized evapotranspiration stress index. Additionally, we investigated the development mechanisms by taking meteorological conditions and soil moisture into account. The findings revealed that the northern Qinghai-Tibet Plateau, western Qilian Mountains, and western and southern Loess Plateau are hotspots of flash droughts, characterized by rapid development rates. Across most of the study area, flash drought events persisted between 25 and 30 days. Adequate precipitation is necessary before the onset of flash droughts in western China, while water scarcity and high temperatures played crucial roles in driving the mid-stage of flash droughts. Within the context of the observed "warming and wetting" trend, the average flash droughts occurrence from 2011 to 2020 was approximately 16 % lower than that from 1981 to 1990, and there was a significant annual decrease in spatial coverage of 0.01 % per year. However, in the "wetting in west, drying in east" trend, the spatial coverage of flash droughts has shifted from a declining trend to an insignificant increasing trend since 2000 in the study area, with significant regional differences between the western and eastern regions. Over the past decade, flash droughts had once again intensified in the central Qinghai-Tibet Plateau and the Loess Plateau due to warming and fluctuating wetting trends, raising significant concerns for future ecosystem and agricultural water management in these regions.
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Efforts in water ecosystem conservation require an understanding of causative factors and removal efficacies associated with mixture toxicity during wastewater treatment. This study conducts a comprehensive investigation into the interplay between wastewater estrogenic activity and 30 estrogen-like endocrine disrupting chemicals (EEDCs) across 12 municipal wastewater treatment plants (WWTPs) spanning four seasons in China. Results reveal substantial estrogenic activity in all WWTPs and potential endocrine-disrupting risks in over 37.5 % of final effluent samples, with heightened effects during colder seasons. While phthalates are the predominant EEDCs (concentrations ranging from
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Disruptores Endócrinos , Poluentes Químicos da Água , Purificação da Água , Estrona , Águas Residuárias , Ecossistema , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Estrogênios/análise , Estradiol , Disruptores Endócrinos/análiseRESUMO
The stomach is a crucial digestive organ in the human body, highly susceptible to inflammation or pathogen invasion, which can lead to various gastric diseases, including gastric cancer. Toll-like receptors (TLRs) are the first line of defense against pathogen invasion. TLR4, a member of the TLRs family, recognizes pathogen and danger-related molecular patterns to induce inflammatory responses. Helicobacter pylori (H. pylori) is a significant factor in gastric health, and TLR4 recognizes H. pylori -LPS to trigger an inflammatory response. Downstream TLR4 signaling generates proinflammatory cytokines that initiate inflammation in the gastric mucosa. In addition, TLR4 gene polymorphisms can increase health risks. This study aims to investigate the contribution of TLR4 to the inflammatory response in gastric diseases and the relation between TLR4 and H. pylori, TLR4 gene polymorphisms, and how TLR4 affects gastric diseases' possible pathways to provide further insight for future prevention and clinical treatment strategies.
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To investigate the growth, mortality, and resource utilization of Gymnocypris chui in Langcuo Lake of Tibetan Plateau, we measured body length and body weight of 389 fish based on four sampling surveys from October 2018 to November 2019. We identified the ages through lapillus. Based on frequency distribution of body length, we estimated the growth and mortality coefficients of G. chui in Langcuo Lake and the utilization status of existing population resources according to the Beverton-Holt dynamic comprehensive model. The results showed that G. chui were mainly composed of individuals aged 2 to 19 years in Langcuo Lake, with a length-body weight relationship equation of W=0.0105L3.042. The von Bertalanffy growth equation revealed that the fish had an asymptotic body length of L∞=37.28 cm, growth coefficient of k=0.160, and theoretical growth starting age of t0=-0.887 a. The total mortality coefficient Z was estimated as 0.48, based on the length-converted catch curve method. According to Pauly's empirical formula, the natural mortality coefficient M was 0.34, fishing mortality coefficient F was 0.14, and exploitation rate E was 0.29, indicating that G. chui resources in Langcuo Lake were not over-exploited. Considering the growth and mortality of G. chui in Langcuo Lake, fishing is appropriate, with a recommended fishing length of Lc=22.37 cm.
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Cyprinidae , Lagos , Animais , Tibet , Peso Corporal , ChinaRESUMO
OBJECTIVE: We investigated the correlation between bone cement distribution and adjacent vertebral fractures (AVFs) after percutaneous vertebroplasty (PVP). METHODS: We retrospectively analyzed patients who underwent single-segment PVP for osteoporotic compression fractures in our hospital from January 2016 to January 2021 and divided the patients into 2 groups, A and B, on the basis of the criterion of whether there were AVFs of the operated vertebrae within 1 year after surgery. We compared the general data of the 2 groups, assessed the ability of 3 simple X-ray-based evaluation methods to predict the occurrence of AVF within 1 year after surgery and derived a simple and accurate evaluation method. RESULTS: A total of 570 patients were included in this study: 511 patients in group A and 59 patients in group B. There were no statistical differences in the general data such as age, gender, and fracture site between the 2 groups. The posterior-anterior (PA), lateral (LAT), and PA and LAT methods showed receiver operating characteristic curve (ROC) predicted postoperative AVF of 0.611, 0.691, and 0.714, respectively. The difference between the area under curve (AUC) of the PA method and LAT method was statistically significant (P = 0.0307), the difference between the AUC of PA method and PA and LAT method was statistically significant (P < 0.001), and the difference between the AUC of LAT method and PA and LAT method was not statistically significant (P = 0.3308).There was no statistical difference between the 2 groups of patients with PA method point of 1 and statistically different between patients with points of 2 and 3. There was statistical difference in points of 1, 2 and 3 in the LAT method between the 2 groups. There was a positive correlation between cement distribution scores and AVF by linear regression analysis of the 3 evaluation methods. CONCLUSIONS: The 3 evaluation methods reliably predict AVF after PVP, with the LAT method, PA and LAT method being more predictive than the PA method, but the LAT method is simpler, with bone cement being widely distributed after crossing the midline in the PA method and contact with the upper and lower end plates in the LAT method being a risk factor for AVF.
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Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Vertebroplastia/efeitos adversos , Vertebroplastia/métodos , Cimentos Ósseos , Estudos Retrospectivos , Correlação de Dados , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/epidemiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Fraturas por Compressão/complicações , Resultado do TratamentoRESUMO
Metal organic framework (MOF)-based adsorbents are appealing for removing low-concentration phosphates with interfering ions in wastewater purification, a new strategy developed to maintain the good activity of metal sites. Here, ZIF-67 was immobilized onto the porous surface of anion exchange resin (D-201) with a high loading amount of 22.0 wt % by a modifiable Co(OH)2 template. We observed that the removal rate of low-concentration phosphate (2 mg P/L) by ZIF-67/D-201 nanocomposites was 98.6%, and more than 90% phosphate adsorption capacity was still maintained, with 5 times molar concentration of interfering ions in the solution. Moreover, after six times of regeneration by solvothermal reaction in the ligand solution, the structure of ZIF-67 was better preserved in D-201 with more than 90% phosphate removal rate. ZIF-67/D-201 could be employed effectively in fixed-bed adsorption runs. By the analysis of experiment and characterization, we found that during the adsorption-regeneration process of ZIF-67/D-201 for phosphate, reversible structural transformation of ZIF-67 and Co3(PO4)2 occurred in D-201. In general, the study reported a new method to develop MOF adsorbents for wastewater treatment.
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Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy.
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BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) metabolism is involved in the entire physiopathological process and is critical to human health. Long-term imbalance in NAD+ homeostasis is associated with various diseases, including non-alcoholic fatty liver disease, diabetes mellitus, cardiovascular diseases, neurodegenerative disorders, aging, and cancer, making it a potential target for effective therapeutic strategies. Currently, several natural products that target NAD+ metabolism have been widely reported to have significant therapeutic effects, but systematic summaries are lacking. PURPOSE: To summarize the latest findings on the prevention and treatment of various diseases through the regulation of NAD+ metabolism by various natural products in vivo and in vitro models, and evaluate the toxicities of the natural products. METHODS: PubMed, Web of Science, and ScienceDirect were searched using the keywords "natural products sources," "toxicology," "NAD+ clinical trials," and "NAD+," and/or paired with "natural products" and "diseases" for studies published within the last decade until January 2023. RESULTS: We found that the natural products mainly include phenols (curcumin, cyclocurcumin, 4-hydroxybenzyl alcohol, salvianolic acid B, pterostilbene, EGCG), flavonoids (pinostrobin, apigenin, acacetin, tilianin, kaempferol, quercetin, isoliquiritigenin, luteolin, silybin, hydroxysafflor yellow A, scutellarin), glycosides (salidroside), quinones (emodin, embelin, ß-LAPachone, shikonin), terpenoids (notoginsenoside R1, ginsenoside F2, ginsenoside Rd, ginsenoside Rb1, ginsenoside Rg3, thymoquinone, genipin), pyrazines (tetramethylpyrazine), alkaloids (evodiamine, berberine), and phenylpropanoids (ferulic acid). These natural products have antioxidant, energy-producing, anti-inflammatory, anti-apoptotic and anti-aging effects, which mainly influence the NAMPT/NAD+/SIRT, AMPK/SIRT1/PGC-1α, Nrf2/HO-1, PKCs/PARPs/NF-κB, and AMPK/Nrf2/mTOR signaling pathways, thereby regulating NAD+ metabolism to prevent and treat various diseases. These natural products have been shown to be safe, tolerable and have fewer adverse effects in various in vivo and in vitro studies and clinical trials. CONCLUSION: We evaluated the toxic effects of natural products and summarized the available clinical trials on NAD+ metabolism, as well as the recent advances in the therapeutic application of natural products targeting NAD+ metabolism, with the aim to provide new insights into the treatment of multiple disorders.
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Produtos Biológicos , Humanos , Animais , NAD/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
Gastric cancer (GC) is a type of the most common cancers. Autoimmune gastritis (AIG) and infection with Helicobacter pylori (HP) are the risk factors of triggering GC. With the emphasis on the treatment of HP, the incidence and prevalence of HP infection in population is decreasing. However, AIG lacks accurate diagnosis and treatment methods, which occupies high cancer risk factors. AIG is controlled by the immune environment of the stomach, including immune cells, inflammatory cells, and infiltrating intercellular material. Various immune cells or cytokines play a central role in the process of regulating gastric parietal cells. Abnormal expression levels of cytokines involved in immunity are bound to face the risk of tumorigenesis. Therefore, it is particularly important for preventing or treating AIG and avoiding the risk of gastric cancer to clarify the confirmed action mode of immune cells and cytokines in the gastric system. Herein, we briefly reviewed the role of the immune environment under AIG, focussing on describing these double-edged effects between immune cells and cytokines, and pointing out potential research challenges.
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Doenças Autoimunes , Gastrite , Helicobacter pylori , Neoplasias Gástricas , Humanos , Citocinas/metabolismo , Gastrite/epidemiologia , Gastrite/etiologia , Células Parietais Gástricas/metabolismo , Helicobacter pylori/metabolismoRESUMO
Cuproptosis is a recently identified controlled process of cell death that functions in tumor development and treatment. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that bind to transcription factors and regulate tumor invasion, penetration, metastasis, and prognosis. However, there are limited data on the function of cuproptosis-associated lncRNAs in pancreatic adenocarcinoma. Utilizing data retrieved from the cancer genome atlas database, we devised a risk prediction model of cuproptosis-associated lncRNAs in pancreatic adenocarcinoma, determined their prognostic significance and relationship with tumor immunity, and screened potential therapeutic drugs. Overall, 178 patients were randomized to a training or test group. We then obtained 6 characteristic cuproptosis-associated lncRNAs from the training group, based on which we constructed the risk prediction model, calculated the risk score, and verified the test group results. Subsequently, we performed differential gene analysis, tumor immunoassays, functional enrichment analysis, and potential drug screening. Finally, we found that the prediction model was highly reliable for the prognostic assessment of pancreatic adenocarcinoma patients. Generally, low risk patients had better outcomes than high risk patients. A tumor immunoassay showed that immunotherapy may benefit high risk patients more as there is a greater likelihood that the tumors could escape the immune system in low-risk patients. Through drug screening, we identified ten drugs that may have therapeutic effects on patients with pancreatic adenocarcinoma. In conclusion, this study constructed a risk prediction model of cuproptosis-associated lncRNAs, which can reliably predict the prognosis of pancreatic adenocarcinoma patients, provided a clinical reference for determining treatment approach, and provided some insights into the associations between lncRNAs and cuproptosis. This provides useful insight to aid in the development of therapeutic drugs for pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma , Apoptose , Neoplasias Pancreáticas , RNA Longo não Codificante , Morte Celular Regulada , Humanos , Adenocarcinoma/metabolismo , Cobre/metabolismo , Imunoterapia , Neoplasias Pancreáticas/metabolismo , Prognóstico , Morte Celular Regulada/fisiologia , RNA Longo não Codificante/metabolismo , Neoplasias PancreáticasRESUMO
In this work, graphene oxide@Fe3O4 (GO@Fe3O4) two-dimensional magnetically oriented nanocomposites were prepared through the co-precipitation approach using graphene oxide as the carrier and FeCl3·6H2O and FeSO4·7H2O as iron sources. The samples were characterized and tested by X-ray diffraction, a transmission electron microscope, Fourier-transform infrared spectroscopy, a vibrating-specimen magnetometer, a polarized optical microscope, an optical microscope, etc. The effects of material ratios and reaction conditions on the coating effects of Fe3O4 on the GO surface were investigated. The stable GO@Fe3O4 sol system was studied and constructed, and the optical properties of the GO@Fe3O4 sol were revealed. The results demonstrated the GO@Fe3O4 two-dimensional nanocomposites uniformly coated with Fe3O4 nanoparticles were successfully prepared. The GO@Fe3O4 two-dimensional nanocomposites exhibited superparamagnetic properties at room temperature, whose coercive force was 0. The stable GO@Fe3O4 sol system could be obtained by maintaining 1 < pH < 1.5. The GO@Fe3O4 sol showed magneto-orientation properties, liquid crystalline properties, and photonic crystal properties under the influence of the external magnetic field. The strength and direction of the magnetic field and the solid content of the GO@ Fe3O4 sol could regulate the aforementioned properties. The results suggest that GO@Fe3O4 two-dimensional magnetically oriented nanocomposites have potential applications in photonic switches, gas barriers, and display devices.