ABSTRACT
Chimeric antigen receptor (CAR)-T-cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR-T-cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR-T-cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR-T-cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR-T-cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR-T-cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR-T-cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates.
Subject(s)
Blood Coagulation Disorders , Hematologic Neoplasms , Immunotherapy, Adoptive , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Hematologic Neoplasms/therapy , Blood Coagulation Disorders/therapy , Blood Coagulation Disorders/etiology , Receptors, Chimeric Antigen/therapeutic useABSTRACT
BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS: Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Subject(s)
Cold Temperature , Hot Temperature , Female , Humans , China/epidemiology , Cities , Mortality , Temperature , Time Factors , Middle Aged , MaleABSTRACT
PURPOSE: To investigate the prognosis value of a combined model based on 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) baseline and interim parameters in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: We retrospectively analyzed the PET metabolic parameters and clinical data of 154 DLBCL patients between December 2015 and October 2020. All of these patients underwent 18F-FDG PET/CT scan before treatment and after three or four courses of chemotherapy. The optimal cut-off values for quantitative variables were determined by the receiver operating characteristic (ROC) curve. The baseline and interim PET/CT parameters, which respectively included maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax) and total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), and clinical characteristics were analyzed by chi-squared test, Kaplan-Meier survival curve, and Cox regression analysis. RESULTS: Of 154 patients, 35 exhibited disease progression or recurrence. ROC analysis revealed that baseline 18F-FDG PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax), along with interim 18F-FDG PET/CT metabolic parameters such as total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), were predictive of relapse or progression in DLBCL patients (P < 0.05). The chi-squared test showed that TMTV0, STMTV0, Dmax, SUVmax1, TMTV1, TTLG1, %ΔSUVmax, Deauville score, IPI, Ann Arbor stage, and LDH were associated with patient prognosis (P < 0.05). Multivariate Cox regression analysis showed that Dmax (P = 0.021) and %ΔSUVmax (P = 0.030) were independent predictors of prognosis in DLBCL patients. There were statistically significant differences in PFS among the three groups with high, intermediate, and low risk according to the combination model (P < 0.001). The combination model presented higher predictive efficacy than single indicators. CONCLUSION: The combined model of baseline parameter Dmax and intermediate parameter %ΔSUVmax of 18F-FDG PET/CT improved the predictive efficacy of PFS and contributed to the risk stratification of patients, providing a reference for clinical individualization and precision treatment.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Humans , Fluorodeoxyglucose F18 , Retrospective Studies , Neoplasm Recurrence, Local , Positron-Emission Tomography , Prognosis , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/drug therapyABSTRACT
The objective of this study was to develop a nomogram including parameters assessed by 18F-FDG PET/CT and clinical parameters for patients with diffuse large B-cell lymphoma (DLBCL) to predict progression-free survival (PFS). A total of 181 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to December 2020 were enrolled in this retrospective study. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate the optimal cutoff values of the semiquantitative parameters (SUVmax, TLG, MTV, and Dmax) for PFS. A nomogram was constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomogram were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The predictive and discriminatory capacities of the nomogram and the International Prognostic Index of the National Comprehensive Cancer Network (NCCN-IPI) were compared via the C-index and AUC. Multivariate analysis demonstrated that male gender and pretreatment Ann Arbor stage III-IV, non-GCB, elevated lactate dehydrogenase (LDH), number of extranodal organ involvement (Neo)>1, MTV≥152.8 cm3, and Dmax ≥53.9 cm were associated with unfavorable PFS (all p<0.05). The nomogram, including gender, Ann Arbor stage, pathology type, Neo, LDH levels, MTV, and Dmax, showed good prediction accuracy, with a C-index of 0.760 (95% CI: 0.727-0.793), which was higher than that of NCCN-IPI (0.710; 95% CI: 0.669-751). The calibration plots for 2-year demonstrated good consistency between the predicted and observed probabilities for survival time. We established a nomogram including MTV, Dmax, and several clinical parameters to predict the PFS of patients with DLBCL, and the nomogram showed better predictability and higher accuracy than NCCN-IPI.
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The skin, the largest organ in the human body, mainly plays a protective role. Once damaged, it can lead to acute or chronic wounds. Wound healing involves a series of complex physiological processes that require ideal wound dressings to promote it. The current wound dressings have characteristics such as high porosity and moderate water vapor permeability, but they are limited in antibacterial properties and cannot protect wounds from microbial infections, which can delay wound healing. In addition, several dressings contain antibiotics, which may have bad impacts on patients. Natural active substances have good biocompatibility; for example, ginsenoside Rg3 has anti-inflammatory, antibacterial, antioxidant, and other biological activities, which can effectively promote wound healing. Some researchers have developed various polymer wound dressings loaded with ginsenoside Rg3 that have good biocompatibility and can effectively promote wound healing and reduce scar formation. This article will focus on the application and mechanism of ginsenoside Rg3-loaded dressings in wounds.
Subject(s)
Polymers , Wound Healing , Humans , Bandages , Anti-Bacterial Agents/pharmacology , HydrogelsABSTRACT
UVB radiation can damage human skin, whereas Ginsenoside Rg3, the active ingredient in red ginseng that is processed from ginseng (Panax ginseng C.A. Meyer), could inhibit UVB induced cell damage through anti-oxidation. Meanwhile, P407/CS/HA hydrogel has significant biomedical applications as carriers of drugs. However, the beneficial effects of Rg3-loaded hydrogel (Rg3-Gel) on human HaCaT keratinocytes induced by UVB have rarely been reported. In our study, Rg3 was loaded into hydrogel and the effect of Rg3-Gel against UVBinduced Hacat cells damages was determined by measuring its ability to alleviate UVBinduced elevation of oxidative stress, pro-inflammatory and apoptotic response. We found that the treatment with Rg3-Gel inhibited the generation of intracellular ROS and MDA and upregulated the expression of antioxidant enzymes SOD and GSH-Px which were inhibited by UVB exposure. Increased levels of pro-inflammatory cytokines TNFα, COX2, iNOS and IL1ß following UVB irradiation were suppressed by the introduction of Rg3-Gel. Additionally, the level of Bcl-2 was decreased and the expression of Bax and Caspase3 were enhanced by Rg3-Gel treatment. In conclusion, Rg3-Gel equipped with the synergistic effect of Rg3 and hydrogel has an effective inhibitory effect on UVB-induced oxidative stress, inflammatory and apoptosis.
Subject(s)
HaCaT Cells , Hydrogels , Humans , HaCaT Cells/metabolism , Hydrogels/pharmacology , Cell Line , Oxidative Stress , Keratinocytes , Inflammation/drug therapy , Inflammation/metabolism , Apoptosis , Ultraviolet Rays/adverse effectsABSTRACT
Objective: We aimed to investigate the effect of Cyclocarya paliurus leaves extracts (CP) on glucose and blood lipid metabolism and its relationship with intestinal flora in type 2 diabetes mellitus (T2DM) patients. Methods: In this open-label, 84-day randomized controlled trial, a total of 38 T2DM patients were randomly assigned to the CP group or the Glipizide group (G group) in a 2:1 ratio. T2DM-associated metabolic phenotypes, gut microbiota and metabolites including short-chain fatty acids (SCFAs) and bile acids (BAs) were detected. Results: At the end of intervention, CP, like Glipizide, significantly improved HbA1c level and other glucose metabolism parameters (fasting plasma glucose (FBG), 2-hour post-meal blood glucose (2hPBG), the area under curve of oral glucose tolerance test glucose (OGTT glucose AUC)). Moreover, CP also resulted in the significant improvement in the levels of blood lipid and blood pressure. Notably, the improvement in blood lipid(triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c)) and blood pressure (diastolic blood pressure (DBP)) was significantly greater in the CP group compared with the G group. Furthermore, the liver and kidney function parameters did not significantly change in both CP group and the G group over the 84-day period. Additionally, the enrichment of potentially beneficial bacteria (Faecalibacterium and Akkermansia), SCFAs and unconjugated BAs and the depletion of potential pathogenic bacteria (Prevotella_9) and conjugated BAs were observed in the CP group, while the abundances of the gut microbial were kept stable in the G group after intervention. Conclusion: CP displays a more beneficial effect in the alleviation of T2DM-associated metabolic phenotypes than glipizide by regulating gut microbiota and metabolites in T2DM patients, with no significant effects on liver and kidney function.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Humans , Diabetes Mellitus, Type 2/metabolism , Glipizide/pharmacology , East Asian People , Lipids , Glucose/pharmacology , Plant Leaves/metabolismABSTRACT
Taking the coral communities of the Xuwen coral reef in 2020 as the research object, we analyzed the species composition, diversity, and interspecific Spearman correlation of the scleractinian coral communities, investigated the features and spatial distribution of the scleractinian coral community, and discussed the correlation between the community composition and environmental factors to identify the affecting factors and their sources. These results showed that (1) compared with the survey in 2004, the coverage of corals in 2020 had significantly decreased, while the dominant genera were still Goniopora and Porites. The coral morphology was massive, and the diversity of the coral community (Shannon-Wiener index, H') was 2.87. The distribution of coral was uneven. The competition among some dominant species of coral was intense. (2) The mass coral bleaching event in the NSCS in August 2020 did not cause severe coral death in the short term on the Xuwen coral reef. (3) The growth of the coral community in 2020 might be greatly affected by high suspended solids and nutrient levels, which were related to the current, mariculture, and coastal erosion. (4) Anthropogenic activities such as coastal aquaculture and fishing were the major factors leading to the reduction in coral coverage on Xuwen coral reef in the past 10 years.
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Background: Omega-3 polyunsaturated fatty acids are known to be associated with numbers of health benefits, and which can be uptake from fish. The aim of this study was to evaluate the current evidence of associations between consumption of fish and diverse health outcomes. Here, we performed an umbrella review to summarize the breadth, strength, and validity of the evidence derived from meta-analyses and systematic reviews of fish consumption on all health outcomes. Methods: The methodological quality of the included meta-analyses and the quality of the evidence were assessed by the Assessment of Multiple Systematic Reviews (AMSTAR) and the grading of recommendations, assessment, development, and evaluation (GRADE) tools, respectively. The umbrella review identified 91 meta-analyses with 66 unique health outcomes, of which 32 outcomes were beneficial, 34 showed nonsignificant associations and only one was harmful (myeloid leukemia). Results: A total of 17 beneficial associations [all-cause mortality, prostate cancer mortality, cardiovascular disease (CVD) mortality, esophageal squamous cell carcinoma (ESCC), glioma, non-Hodgkin lymphoma (NHL), oral cancer, acute coronary syndrome (ACS), cerebrovascular disease, metabolic syndrome, age-related macular degeneration (AMD), inflammatory bowel disease (IBD), Crohn's disease (CD), triglycerides, vitamin D, high-density lipoprotein (HDL)-cholesterol, and multiple sclerosis (MS)], and eight nonsignificant associations [colorectal cancer (CRC) mortality, esophageal adenocarcinoma (EAC), prostate cancer, renal cancer, ovarian cancer, hypertension, ulcerative colitis (UC), and rheumatoid arthritis (RA)] were evaluated as moderate/high quality of evidence. According to dose-response analyses, consumption of fish, especially fatty types, seems generally safe at one-two servings per week and could exert protective effects. Conclusions: Fish consumption is often associated with a variety of health outcomes, both beneficial and harmless, but only about 34% of the associations were graded as based on a moderate/high quality of evidence, and additional multicenter high quality randomized controlled trials (RCTs) with a large sample size are needed to verify these findings in the future.
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BACKGROUND: With complex changes in the global climate, it is critical to understand how ambient temperature affects health, especially in China. We aimed to assess the effects of temperature on daily mortality, including total non-accidental, cardiovascular disease (CVD), respiratory disease, cerebrovascular disease, and ischemic heart disease (IHD) mortality between 2016 and 2020 in Chengdu, China. METHODS: We obtained daily temperature and mortality data for the period 2016-2020. A Poisson regression model combined with a distributed-lag nonlinear model was used to examine the association between temperature and daily mortality. We investigated the effects of individual characteristics by sex, age, education level, and marital status. RESULTS: We found significant non-linear effects of temperature on total non-accidental, CVD, respiratory, cerebrovascular, and IHD mortality. Heat effects were immediate and lasted for 0-3 days, whereas cold effects persisted for 7-10 days. The relative risks associated with extreme high temperatures (99th percentile of temperature, 28 °C) over lags of 0-3 days were 1.22 (95% confidence interval [CI]: 1.17, 1.28) for total non-accidental mortality, 1.40 (95% CI: 1.30, 1.50) for CVD morality, 1.34 (95% CI: 1.24, 1.46) for respiratory morality, 1.33 (95% CI: 1.20, 1.47) for cerebrovascular mortality, and 1.38 (95% CI: 1.20, 1.58) for IHD mortality. The relative risks associated with extreme cold temperature (1st percentile of temperature, 3.0 °C) over lags of 0-14 days were 1.32 (95% CI: 1.19, 1.46) for total mortality, 1.45 (95% CI: 1.24, 1.68) for CVD morality, 1.28 (95% CI: 1.09, 1.50) for respiratory morality, 1.36 (95% CI: 1.09, 1.70) for cerebrovascular mortality, and 1.26 (95% CI: 0.95, 1.68) for IHD morality. We found that hot and cold affects were greater in those over 85 years of age, and that women, individuals with low education levels, and those who were widowed, divorced, or never married, were more vulnerable. CONCLUSIONS: This study showed that exposure to hot and cold temperatures in Chengdu was associated with increased mortality, with people over 85 years old, women, those with low education levels, and unmarried individuals being more affected by hot and cold temperatures.
Subject(s)
Cardiovascular Diseases , Myocardial Ischemia , Humans , Female , Aged , Aged, 80 and over , Temperature , Time Factors , Hot Temperature , Cold Temperature , China/epidemiology , Nonlinear Dynamics , MortalityABSTRACT
It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Here we report on the efficacy and safety of donor CD7 chimeric antigen receptor (CAR) T cell therapy (CAR-T) bridging to allo-HSCT in treating 12 patients with relapsed/refractory (r/r) T-ALL or T-cell lymphoblastic lymphoma (T-LBL). The median time from CAR-T infusion to allo-HSCT was 33.5 days (range, 30 to 55 days). With reduced-intensity conditioning, all patients except 1 successfully engrafted. With a mean follow-up of 301 days (range, 238 to 351 days), the remaining 11 patients were alive and disease-free at their last follow-up. Acute graft-versus-host disease (GVHD) was observed in 3 patients, and chronic GVHD developed in 3 patients, all with a limited pattern. Under the current protocol, infection was the main complication post-transplantation, and all infections were well controlled except in 1 patient, who died of multiple organ failure caused by an infection-induced inflammatory cytokine storm at days 14 post-transplantation. One patient relapsed (CD7+), and 3 patients became minimal residual disease (MRD) positive (CD7+ in 1, CD7- in 1, fusion gene positive only in 1). Subsequently, all 3 of these patients achieved an MRD-negative complete remission with either CD7 CAR-T reinfusion or immunosuppressive agent withdrawal. Our study shows for the first time that a novel strategy of donor CD7 CAR-T bridging to allo-HSCT can be highly effective and feasible in improving disease-free survival for patients with r/r T-ALL or T-LBL.
Subject(s)
Graft vs Host Disease , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Humans , Antigens, CD7 , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , T-Lymphocytes , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/therapyABSTRACT
OBJECTIVE: To investigate the prognostic value of interim 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (â³SUVmax%) cut-off value. The prognostic value of â³SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum â³SUV max% cut-off value was 74.9%. Patients with â³SUVmax%≥74.9% had a lower rate of progression or recurrence than those with â³SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). â³SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). â³SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), â³SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that â³SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION: Both 5-PS and â³SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of â³SUVmax% is superior to that of 5-PS.
Subject(s)
Fluorodeoxyglucose F18 , Lymphoma, Large B-Cell, Diffuse , Fluorodeoxyglucose F18/therapeutic use , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/drug therapy , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Prognosis , Retrospective StudiesABSTRACT
Background: Diabetic ulcer remains a clinical challenge due to impaired angiogenesis and persistent inflammation, requiring new alternative therapies to promote tissue regeneration. Purpose: In this study, chitosan/sodium alginate/velvet antler blood peptides (CS/SA/VBPs) hydrogel (CAVBPH) was fabricated and used in the treatment of skin wounds in type 2 diabetes mellitus (T2D) for the first time. Methods: VBPs were prepared by hydrolysis and ultrafiltration, and their sequences were identified using LC-MS/MS. The CAVBPH was further fabricated and characterized. A mouse model of T2D was induced by a high-sugar and high-fat diet (HSFD) and streptozotocin (STZ) injection. CAVBPH was applied topically to T2D wounds, and its effects on skin repair and potential biological mechanisms were analyzed by appearance observation, histopathological staining, bioinformatics analysis, Western blot, and 16S rRNA sequencing. Results: VBPs had numerous short-chain active peptides, excellent antioxidant activity, and a low hemolysis rate. CAVBPH exhibited desirable biochemical properties and participated in the diabetic wound healing process by promoting cell proliferation (PCNA and α-SMA) and angiogenesis (capillaries and CD31) and alleviating inflammation (CD68). Mechanistically, the therapeutic effect of CAVBPH on chronic wounds might rely on activating the PI3K/AKT/mTOR/HIF-1α/VEGFA pathway and reversing the expression of inflammatory cytokines TNF-α and IL-1ß. The results of 16S rRNA sequencing indicated that T2D significantly altered the diversity and structure of skin flora at the wound site. CAVBPH treatment elevated the relative abundance of beneficial microbes (e.g., Corynebacterium_1 and Lactobacillus) and reversed the structural imbalance of skin microbiota. Conclusion: These results indicate that CAVBPH is a promising wound dressing, and its repair effect on diabetic wounds by regulating angiogenesis, inflammatory response, and skin flora may depend on the rich small peptides in VBPs.
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INTRODUCTION: We aimed to assess the effects of 2 isoenergetic intervention diets (a freshwater fish-based diet [F group] or freshwater fish-based and red meat-based diets alternately [F/M group]) on liver steatosis and their relationship with intestinal flora in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: In this open-label, 84-day randomized controlled trial, 34 NAFLD patients with hepatic steatosis ≥10% were randomly assigned to the F group or F/M group in a 1:1 ratio using a computer-generated random number allocation by a researcher not involved in the study. Liver fat content and gut microbiota and its metabolites were measured. RESULTS: At the end of intervention, the absolute reduction of hepatic steatosis was significantly greater in the F group than in the F/M group (-4.89% vs -1.83%, P = 0.032). Of the 16 secondary clinical outcomes, the improvement in 7 in the F group was greater compared with the F/M group, including alanine aminotransferase and gamma-glutamyl transferase. Furthermore, dietary freshwater fish and red meat consumption alternately did not exacerbate NAFLD. Moreover, changes in the enrichment of Faecalibacterium, short-chain fatty acids, and unconjugated bile acids and the depletion of Prevotella 9 and conjugated bile acids in the F group were significantly greater compared with the F/M group. DISCUSSION: Higher intake of freshwater fish may be beneficial to NAFLD by regulating gut microbiota and its metabolites, whereas intake of a similar total of animal protein and fat from the alternating freshwater fish and red meat may not be harmful for NAFLD in the dietary management of patients with NAFLD.
Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Alanine Transaminase/metabolism , Animals , Bile Acids and Salts/metabolism , China , Diet , Fresh Water , Humans , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolismABSTRACT
BACKGROUND: Ginseng is deemed to be an effective anti-aging therapy. Evidence for differences in representative active ingredients and anti-aging effects between garden ginseng (GG) and ginseng under forest (FG) is insufficient. PURPOSE: The study was designed to systematically analyze the differences in the mechanistic protective effects of GG and FG on aging mice based on their compositional differences. METHODS: The chemical ingredients in GG and FG were first determined. In vivo, D-galactose-induced aging mice were orally administered GG or FG (400 mg/kg/day) for 6 weeks. Behavioral parameters of mice were measured by the radial 8-arm maze, and the changes in body weight and organ indices were recorded. Blood, brain tissue, and feces were collected for biochemical analysis, histopathological staining, Western blotting, and 16S rDNA intestinal flora sequencing, respectively. RESULTS: The absolute contents of total ginsenosides, polyphenols, crude polysaccharides, starch, and protein in GG were 0.71, 0.68, 1.15, 2.27, and 1.08 folds higher than those in FG, respectively; while FG exhibited a higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) but lower relative content of starch than GG. GG and FG improved hippocampal lesions and poor weight gain, organ indices, and behavioral indices, and prevented excessive oxidative stress and acetylcholinesterase activity in aging mice. What's more, GG and FG treatment ameliorated excessive apoptosis and inflammatory reaction in the aging brain by modulating apoptosis-related proteins, PI3K/AKT/mTOR pathway, and SIRT1/NF-κB pathway. GG and FG also restored the diversity and structure of gut microbiota, up-regulated the relative abundance of beneficial bacteria (e.g., Lactobacillus), and tended to exert key anti-aging effects via the microbiota-gut-brain axis. Notably, in vivo experiments confirmed that FG had a stronger anti-aging activity than GG. CONCLUSION: FG exerts a more powerful anti-aging effect than GG by regulating oxidative stress, apoptosis, inflammation, and the microbe-gut-brain axis, possibly relying on the higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) in FG.
Subject(s)
Gastrointestinal Microbiome , Ginsenosides , Panax , Acetylcholinesterase , Aging , Animals , Forests , Gardens , Mice , NF-kappa B , Phosphatidylinositol 3-Kinases , Polysaccharides , Proto-Oncogene Proteins c-akt , Sirtuin 1 , Starch , TOR Serine-Threonine KinasesABSTRACT
Objective: To assess the effects of dietary white meat (grass carp and chicken) and red meat (pork and beef) on metabolic parameters, including the intestinal microbiota and its metabolites (SCFAs and bile acids) in NAFLD rats induced by high-fat diet. Methods: NAFLD rats were randomly assigned to five groups: NAFLD group, grass carp group, chicken group, pork group, and beef group (10 rats in each group), and these rats were fed for 8 weeks using the high-fat diet, grass carp-based diet, chicken-based diet, pork-based diet, and beef-based diet, respectively. At the end of the intervention, NAFLD-related metabolic indexes, intestinal flora, and its metabolites were measured. Results: The grass carp-based diet significantly improved hepatic pathological changes and glycolipid metabolism, and the chicken-based diet only partially improved the metabolic parameters. However, NAFLD progression was observed in the pork group and the beef group. What is more, the white meat-based diet-mediated changes in the enrichment of beneficial bacteria (such as Lactobacillus or Akkermansia), SCFAs, and unconjugated BAs (such as UDCA) and the depletion of pathogenic bacteria (such as Bilophila and Prevotella_9) and conjugated BAs were observed, while the red meat-based diet-induced changes in the enrichment of pathogenic bacteria (Prevotella_9 or Lachnospiraceae_UCG-010) and conjugated BAs and the depletion of SCFAs and unconjugated BAs were found. Conclusion: The dietary white meat and red meat modulating gut microbiota and its metabolites may favor and aggravate NAFLD in rats, respectively.
Subject(s)
Carps , Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Red Meat , Animals , Cattle , Chickens , Diet, High-Fat , RatsABSTRACT
Wounds caused by accidents and surgery are inevitable, and inflammation and microbial infection during the healing process are serious clinical challenges, resulting in slow wound healing. In this study, we created a 37 °C-sensitive hydrogel using poloxamer, chitosan and hyaluronic acid, loaded with the active substance dihydromyricetin, and further evaluated its potential for wound healing. The hydrogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and thermogravimetric analysis for their micromorphological structure, characteristic functional groups, crystal structure and thermal stability, and in vitro drug release assays showed that the hydrogel could slowly release dihydromyricetin. In addition, the hydrogels were found to exhibit good biocompatibility and significant in vitro antioxidant and anti-inflammatory activity according to hemolysis, in vitro antioxidant and anti-inflammatory tests. Methyl thiazolyl tetrazole cytotoxicity tests verified that the film was non-toxic to human keratinocyte (HaCaT) cells, while in vivo experiments showed that this hydrogel could promote skin repair by promoting skin-associated growth factor expression and inhibiting nuclear factor kappa B-mediated cellular inflammatory factors. These results demonstrated that the temperature-sensitive hydrogels loaded with dihydromyricetin could serve as potential candidates for guided skin repair.
Subject(s)
Chitosan , Hydrogels , Antioxidants/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Flavonols , Humans , Hyaluronic Acid , Hydrogels/chemistry , Hydrogels/pharmacology , Poloxamer , Wound HealingABSTRACT
Skin wound healing is a principal clinical challenge, and it is necessary to develop effective alternative treatments. Excessive inflammatory response is linked to delayed healing. This study was the first to report a multi-functional chitosan/sodium alginate/velvet antler blood peptides (VBPs) hydrogel (CAVBPH) and explore its potential mechanism to promote wound healing. The results showed that CAVBPH possessed desirable characteristics including thermo-sensitivity, antioxidation, antibacterial activity, biosafety, VBPs release behavior, etc., and significantly accelerated skin wound healing in mice. Specifically, the CAVBPH treatment enhanced cell proliferation, angiogenesis, and extracellular matrix (ECM) secretion, and also relieved inflammation at the wound site compared to the PBS-treated group and blank hydrogel scaffold-treated group. Mechanistically, the efficacy of CAVBPH might be related to the activation of the PI3K/AKT/mTOR and SIRT1/NF-κB pathways. Overall, CAVBPH seems to be a promising therapy for skin repair, probably relying on the abundant short-chain peptides in VBPs.
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Ginsenoside Rg3 has shown beneficial effects in various skin diseases. The current interest in designing and developing hydrogels for biomedical applications continues to grow, inspiring the further development of drug-loaded hydrogels for tissue repair and localized drug delivery. The aim of the present study was to develop an effective and safe hydrogel (Rg3-Gel), using ginsenoside Rg3, and we evaluated the wound-healing potential and therapeutic mechanism of Rg3-Gel. The results indicated that the optimized Rg3-Gel underwent discontinuous phase transition at low and high temperatures. Rg3-Gel also exhibited good network structures, swelling water retention capacity, sustainable release performance, and excellent biocompatibility. Subsequently, the good antibacterial and antioxidant properties of Rg3-Gel were confirmed by in vitro tests. In full-thickness skin defect wounded models, Rg3-Gel significantly accelerated the wound contraction, promoted epithelial and tissue regeneration, and promoted collagen deposition and angiogenesis. In addition, Rg3-Gel increased the expression of autophagy proteins by inhibiting the MAPK and NF-KB pathways in vivo. It simultaneously regulated host immunity by increasing the abundance of beneficial bacteria and the diversity of the wound surface flora. From these preliminary evaluations, it is possible to conclude that Rg3-Gel has excellent application potential in wound-healing drug delivery systems.