ABSTRACT
BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 µg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (ß = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (ß = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (ß = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (ß = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (ß = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (ß = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls. CONCLUSIONS: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.
Subject(s)
Exercise , Humans , Female , Male , Middle Aged , Exercise/physiology , Aged , Dietary Proteins/administration & dosage , Body Composition , Muscle, Skeletal/physiologyABSTRACT
Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.
Subject(s)
Anti-Bacterial Agents , Flavonoids , Gastrointestinal Microbiome , Lincomycin , MAP Kinase Signaling System , Animals , Flavonoids/pharmacology , Flavonoids/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Gastrointestinal Microbiome/drug effects , Swine , MAP Kinase Signaling System/drug effects , Lincomycin/pharmacology , Mice , Dysbiosis/chemically induced , Dysbiosis/drug therapy , Male , Intestines/drug effects , Intestines/pathologyABSTRACT
The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models. To fulfill our design, we utilized the CXCR4/CXCL12 biological axis and biomimetic cell membranes in conjunction with self-stimulated phototherapy. This nanoreactor possesses the capability to migrate into the bone marrow cavity, inhibit AML cells from infiltrating into the visceral organ, significantly enhance the antileukemia effect, and prolong the survival time of leukemic mice. Therefore, this nanoreactor has significant potential for achieving high success rates and low recurrence rates in leukemia treatment.
Subject(s)
Leukemia, Myeloid, Acute , Photochemotherapy , Receptors, CXCR4 , Animals , Receptors, CXCR4/metabolism , Receptors, CXCR4/antagonists & inhibitors , Mice , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/therapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Cell Line, Tumor , Chemokine CXCL12/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacologyABSTRACT
BACKGROUND: The utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens. RESULTS: Dietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition. CONCLUSIONS: The results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis. Video Abstract.
Subject(s)
Fatty Acids , Morus , Animals , Female , Fatty Acids/metabolism , Egg Yolk/metabolism , Morus/metabolism , Lipid Metabolism , Chickens/metabolism , Diet , Fatty Acids, Unsaturated/metabolism , Animal Feed/analysis , Dietary SupplementsABSTRACT
As ethnic medicine, the whole grass of plants in Cirsium was used as antimicrobial. This review focuses on the antimicrobial activity of plants in Cirsium, including antimicrobial components, against different types of microbes and bacteriostatic mechanism. The results showed that the main antimicrobial activity components in Cirsium plants were flavonoids, triterpenoids and phenolic acids, and the antimicrobial ability varied according to the species and the content of chemicals. Among them, phenolic acids showed a strong antibacterial ability against Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium. The antibacterial mechanisms include: (1) damaging the cell membrane, cell walls, mitochondria and nucleus of bacteria; (2) inhibiting the synthesis of proteins and nucleic acids; (3) suppressing the synthesis of enzymes for tricarboxylic acid cycle pathways and glycolysis, and then killing the bacteria via inhibition of energy production. Totally, most research results on antimicrobial activity of Cirsium plants are reported based on in vitro assays. The evidence from clinical data and comprehensive evaluation are needed.
Subject(s)
Anti-Bacterial Agents , Cirsium , Cirsium/chemistry , Anti-Bacterial Agents/pharmacology , HumansABSTRACT
Betaine is widely used as a feed additive in the chicken industry to promote laying performance and growth performance, yet it is unknown whether betaine can be used in geese to improve the laying performance of goose breeders and the growth traits of offspring goslings. In this study, laying goose breeders at 39 wk of age were fed basal (Control, CON) or betaine-supplemented diets at low (2.5 g/kg, LBT) or high (5 g/kg, HBT) levels for 7 wk, and the breeder eggs laid in the last week were collected for incubation. Offspring goslings were examined at 35 and 63 d of age. The laying rate tended to be increased (Pâ =â 0.065), and the feed efficiency of the breeders was improved by betaine supplementation, while the average daily gain of the offspring goslings was significantly increased (Pâ <â 0.05). Concentrations of insulin-like growth factor 2 (IGF-2) in serum and liver were significantly increased in the HBT group (Pâ <â 0.05), with age-dependent alterations of serum T3 levels. Concurrently, hepatic mRNA expression of the IGF gene family was significantly increased in goslings derived from betaine-treated breeders (Pâ <â 0.05). A higher ratio of proliferating cell nuclear antigen (PCNA)-immunopositive nuclei was found in the liver sections of the HBT group, which was confirmed by significantly upregulated hepatic expression of PCNA mRNA and protein (Pâ <â 0.05). Moreover, hepatic expression of thyroxine deiodinase type 1 (Dio1) and thyroid hormone receptor ß (TRß) was also significantly upregulated in goslings of the HBT group (Pâ <â 0.05). These changes were associated with significantly higher levels of global DNA 5-mC methylation, together with increased expression of methyl transfer genes (Pâ <â 0.05), including betaine-homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT), and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). The promoter regions of IGF-2 genes, as well as the predicted TRß binding site on the IGF-2 gene, were significantly hypomethylated (Pâ <â 0.05). These results indicate that gosling growth can be improved by dietary betaine supplementation in goose breeders via epigenetic modulation of the IGF gene family, especially IGF-2, in the liver.
The goose industry plays important roles in economics, cultures, and ecosystems, yet the low laying and growth rates of many indigenous breeds hinders the development of the goose farming. Betaine, an important methyl donor, is commonly used as a feed additive in livestock and poultry to enhance animal growth. Dietary supplementation of betaine in laying hens or gestational sows has been reported to promote the growth of their offspring. Here, we sought to investigate whether and how dietary betaine supplementation affects the growth and development of offspring goslings. In this study, goose breeders, both male and female, were fed a basal diet supplemented respectively with 0, 2.5, or 5 g/kg betaine for 7 wk. Goslings hatched from the breeder eggs of different groups were raised under the same standard condition for assessing the growth performance. Parental betaine increases the growth rate of offspring goslings with decreased DNA methylation on the IGF-2 gene promoter and increased expression of the IGF-2 gene in the liver. These results provide scientific evidence for the inter-generational effect of betaine on gosling growth.
Subject(s)
Betaine , Insulin-Like Growth Factor II , Animals , Betaine/pharmacology , Insulin-Like Growth Factor II/genetics , Geese/genetics , Geese/metabolism , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Ovum/metabolism , Dietary Supplements , Liver/metabolism , Diet/veterinary , Chickens/genetics , Chickens/metabolism , Epigenesis, Genetic , RNA, Messenger/metabolism , Animal Feed/analysisABSTRACT
This experiment was conducted to evaluate the effects of including a mixed-dimensional attapulgite clay (MDA) into a naturally moldly diet for Hu lambs. Fifty male Hu lambs with similar initial body weight (28.24â ±â 1.80 kg) were randomly allocated into five dietary treatments: a basal diet containing naturally occurring mycotoxins with 0, 0.5, 1.0, and 2.0 kg/t MDA, and basal diet with a commercial mycotoxin adsorbent Solis with montmorillonite as the major component at 1 kg/t. Both MDA and Solis increased average daily gain (ADG) and dry matter intake (DMI; Pâ ≤â 0.004), and there was no difference in growth performance between MDA and Solis (Pâ ≥â 0.26). The final body weight, DMI, and ADG were linearly increased with increasing MDA supplementation (Pâ <â 0.01). Lambs treated with both MDA and Solis demonstrated greater apparent digestibility of dry matter (DM), organic matter (OM), and energy compared with the control group (Pâ ≤â 0.03), and there were no differences in nutrient digestibilities between MDA and Solis (Pâ ≥â 0.38). Digestibility of CP was linearly increased with the increasing MDA supplementation (Pâ =â 0.01). Neither MDA nor Solis affected rumen total volatile fatty acid (TVFA) concentration (Pâ ≥â 0.39), but decreased the acetate-to-propionate ratio and molar proportion of n-butyrate (Pâ ≤â 0.01), and MDA also increased the concentration of ammonia (Pâ =â 0.003). Besides, increasing MDA supplementation linearly reduced the acetate-to-propionate ratio and molar proportion of n-butyrate (Pâ =â 0.01), but linearly and quadratically increased the concentration of ammonia (Pâ ≥â 0.003). These results showed that the incorporation of MDA into a naturally moldy diet of Hu lambs yielded comparable results to the Solis product, with higher growth performance and nutrient digestibility but lower acetate-to-propionate ratio observed. In conclusion, includingâ ≥â 1 kg/t of MDA in high mycotoxin risk diets for growing lambs improves feed intake and rumen fermentation.
The issue of mycotoxin-contaminated animal feed has consistently presented a significant challenge in relation to animal health and production. The mixed-dimensional attapulgite clay (MDA) has been proven effective in binding polar mycotoxins such as aflatoxin, while also effectively adsorbing hydrophobic or weakly polar mycotoxins such as zearalenone (ZEN) and ochratoxin. Therefore, this study was undertaken to assess the impact of MDA inclusion in mycotoxin-contaminated diets on performance and rumen fermentation variables in lambs. The results indicated that MDA not only significantly improved the growth performance and nutrient digestibility of Hu lambs but also enhanced the molar proportion of propionate and ammonia concentration, and reduced the acetate to propionate ratio and the molar proportion of n-butyrate.
Subject(s)
Magnesium Compounds , Mycotoxins , Rumen , Silicon Compounds , Sheep , Animals , Male , Clay , Rumen/metabolism , Propionates/metabolism , Fermentation , Ammonia/metabolism , Digestion , Diet/veterinary , Sheep, Domestic , Eating , Acetates/metabolism , Butyrates/metabolism , Body Weight , Animal Feed/analysisABSTRACT
It is well known that Japan's population is aging, and the number of people older than 75 years is increasing significantly. Since older people, especially old individuals, are often multimorbid and cannot be always successfully treated and cared for by individual organ-specific treatment, it is essential to utilize knowledge of geriatrics when treating such older patients. Therefore, it is indisputable that education on geriatric medicine is extremely important in Japan, which is the country with the largest aging population. However, the number of universities in Japan that offer geriatrics courses is decreasing. This means that many medical students become doctors without learning the essential characteristics of medical care for older patients despite the need for prompt treatment of older patients in clinical practice in Japan, which is a major obstacle to the development of geriatric medicine in Japan. Here, we review the current status of geriatrics in Japan and overseas and consider the future of geriatrics education to provide holistic and cost-effective medical care for older patients and improve their quality of life and well-being.
ABSTRACT
OBJECTIVE: Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg. METHODS: Hemiparkinsonian mice model was established through the injection of 6-OHDA into the striatum. Mice were pretreated with calcitriol before 6-OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro-inflammatory cytokines levels, T-cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo. RESULTS: We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6-OHDA-induced PD model. Mechanistically, calcitriol promoted anti-inflammatory/neuroprotective Treg and inhibited pro-inflammatory/neurodestructive effector T-cell generation in this model. This process significantly inhibited T-cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro-inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti-inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody-mediated Treg depletion assay. As predicted, the anti-inflammatory effects of calcitriol in the PD model were diminished following Treg depletion. CONCLUSION: These findings suggest that calcitriol's anti-inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.
Subject(s)
Microglia , Parkinson Disease , Mice , Animals , Dopamine/metabolism , Calcitriol/pharmacology , T-Lymphocytes, Regulatory/metabolism , Oxidopamine/metabolism , Oxidopamine/pharmacology , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Anti-Inflammatory Agents/pharmacology , Dopaminergic Neurons , Cytokines/metabolism , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. AIM OF THE STUDY: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. MATERIALS AND METHODS: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. RESULTS: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 µg mL-1) in vivo. q-PCR data demonstrated that DGSN decoction (500 µg mL-1) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo. CONCLUSION: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.
Subject(s)
Angelica sinensis , Drugs, Chinese Herbal , Thrombosis , Female , Animals , Zebrafish , Blood Coagulation Factors , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Prothrombin , Thrombosis/drug therapy , RNAABSTRACT
BACKGROUND: Obesity and related metabolic diseases are becoming a worldwide epidemic, leading to increased mortality and heavy medical costs. Our Chinese herbal formula Xiao-Gao-Jiang-Zhuo (XGJZ) has remarkable effects on curing obese patients in the clinic, but the cellular and molecular basis remains unknown. This study aimed to reveal the molecular mechanism involved in adipogenesis in vitro. METHODS: Chinese herbal formula XGJZ-containing serum was prepared from XGJZ-treated obesity model rats. The function of XGJZ-containing serum was validated in 3T3-L1 preadipocytes. Oil O staining was performed to determine intracellular lipid accumulation in differentiated 3T3-L1 cells. The expression of pro-adipogenic transcription factors was measured to further validate the adipogenesis of 3T3-L1 adipocytes. The contents of triglyceride (TG), free fatty acid (FFA), and glycerin, along with the activities of lipid metabolism-related enzymes (including FAT, FATP1, DGAT, GPAT, ATGL, and HSL) were measured to study the lipogenesis in 3T3-L1 adipocytes. RESULTS: XGJZ-containing serum inhibited 3T3-L1 differentiation, decreased intracellular lipid accumulation, and suppressed the expression of pro-adipogenic transcription factors in differentiated 3T3-L1 cells. The contents of TG, FFA, and glycerin were decreased when treated with XGJZ-containing serum, which also modulated lipid metabolism-related enzyme activities. The activities of fatty acid transporters (FAT, FATP1) and lipid mobilization enzymes (ATGL, HSL) were promoted, while activities of triglyceride biosynthesis enzymes (DGAT, GPAT) were attenuated in differentiated 3T3-L1 cells. CONCLUSION: XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes, affirming the effect of XGJZ in treating obesity. It provides evidence for the mechanism of obesity.
Subject(s)
Adipogenesis , Glycerol , Humans , Mice , Rats , Animals , 3T3-L1 Cells , Glycerol/metabolism , Glycerol/pharmacology , Obesity , Triglycerides , Transcription Factors , PPAR gamma/metabolismABSTRACT
Tea (Camellia sinensis) is a highly important beverage crop renowned for its unique flavour and health benefits. Chlorotic mutants of tea, known worldwide for their umami taste and economic value, have gained global popularity. However, the genetic basis of this chlorosis trait remains unclear. In this study, we identified a major-effect quantitative trait locus (QTL), qChl-3, responsible for the chlorosis trait in tea leaves, linked to a non-synonymous polymorphism (G1199A) in the magnesium chelatase I subunit (CsCHLI). Homozygous CsCHLIA plants exhibited an albino phenotype due to defects in magnesium protoporphyrin IX and chlorophylls in the leaves. Biochemical assays revealed that CsCHLI mutations did not affect subcellular localization or interactions with CsCHLIG and CsCHLD. However, combining CsCHLIA with CsCHLIG significantly reduced ATPase activity. RNA-seq analysis tentatively indicated that CsCHLI inhibited photosynthesis and enhanced photoinhibition, which in turn promoted protein degradation and increased the amino acid levels in chlorotic leaves. RT-qPCR and enzyme activity assays confirmed the crucial role of asparagine synthetase and arginase in asparagine and arginine accumulation, with levels increasing over 90-fold in chlorotic leaves. Therefore, this study provides insights into the genetic mechanism underlying tea chlorosis and the relationship between chlorophyll biosynthesis and amino acid metabolism.
Subject(s)
Anemia, Hypochromic , Camellia sinensis , Lyases , Camellia sinensis/genetics , Camellia sinensis/metabolism , Chlorophyll/metabolism , Tea/metabolism , Amino Acids/metabolism , Mutation , Anemia, Hypochromic/metabolism , Plant Leaves/genetics , Plant Leaves/metabolismABSTRACT
Weaning is one of the major factors that cause stress and intestinal infection in infants and in young animals due to an immature intestine and not fully developed immune functions. Pectin (PEC), a prebiotic polysaccharide, has attracted considerable attention in intestinal epithelial signaling and function via modulation of the microbial community. A total of 16 weaned piglets (21-d-old) were randomly assigned into two groups: control group and PEC group. Supplementation of 5% pectin improved intestinal mucosal barrier function by modulating the composition of the bile acid pool in piglets. Specifically, piglets in PEC group had less serum D-lactate content and alkaline phosphatase activity. In the ileum, dietary pectin increased the number of crypt PAS/AB-positive goblet cells and the mRNA expressions of MUC2, ZO-1, and Occludin. Piglets in PEC group displayed a decreased abundance of Enterococcus (2.71 vs. 65.92%), but the abundances of Lactobacillus (30.80 vs. 7.93%), Streptococcus (21.41 vs. 14.81%), and Clostridium_sensu_stricto_1 (28.34 vs. 0.01%) were increased. Elevated concentrations of bile acids especially hyocholic acid species (HCAs) including HCA, HDCA, and THDCA were also observed. Besides, correlation analysis revealed that dietary pectin supplementation may have beneficial effects through stimulation of the crosstalk between gut microbes and bile acid synthesis within the enterohepatic circulation. Thus, dietary pectin supplementation exhibited a further positive effect on the healthy growth and development of weaned piglets. These findings suggest pectin supplementation as the prebiotic is beneficial for gut health and improvement of weaned stress via regulating microbiota and bile acid metabolism.
Subject(s)
Dietary Supplements , Intestinal Barrier Function , Humans , Animals , Swine , Dietary Supplements/analysis , Pectins/pharmacology , Diet , Bile Acids and Salts , WeaningABSTRACT
Peroxymonosulfate-mediated advanced oxidation processes (PMS-AOPs) degrading organic pollutants (Tetracycline (TC) as an example) in water with singlet oxygen (1O2) as the main reactive oxygen has received more and more attention. However, the generation mechanism of 1O2 is still unclear. Consequently, this study investigates the 1O2 formation mechanism during the activated PMS process using a nitrogen-copper-loaded carbon-based material (Cu0/Cu2O/CuO@N-C), synthesized by thermally decomposing organobase-modified HKUST-1 via a one-pot method. It was discovered that incorporating an organobase (Benzylamine) into the metal organic framework (MOF) precursor directs the MOF's self-assembly process and supplements its nitrogen content. This modification modulates the Nx-Cu-Oy active site formation in the material, selectively producing 1O2. Additionally, 1O2 was identified as the dominant reactive oxygen species in the Cu0/Cu2O/CuO@N-C-PMS system, contributing to TC degradation with a rate of 70.82%. The TC degradation efficiency remained high in the pH range of 3-11 and sustained its efficacy after five consecutive uses. Finally, based on the intermediates of TC degradation, three possible degradation pathways were postulated, and a reduction in the ecotoxicity of the degradation products was predicted. This work presents a novel and general strategy for constructing nitrogen-copper-loaded carbon-based materials for use in PMS-AOPs.
Subject(s)
Copper , Environmental Pollutants , Peroxides/chemistry , Tetracycline/chemistry , Anti-Bacterial Agents , Oxygen , Carbon , NitrogenABSTRACT
Antibacterial drug resistance of gram-negative bacteria (GNB) results in high morbidity and mortality of GNB infection, seriously threaten human health globally. Developing new antibiotics has become the critical need for dealing with drug-resistant bacterial infections. Cefiderocol is an iron carrier cephalosporin that achieves drug accumulation through a unique "Trojan horse" strategy into the bacterial periplasm. It shows high antibacterial activity against multidrug-resistant (MDR) Enterobacteriaceae and MDR non-fermentative bacteria. The application of cefiderocol offers new hope for treating clinical drug-resistant bacterial infections. However, limited clinical data and uncertainties about its resistance mechanisms constrain the choice of its therapeutic use. This review aimed to summarize the clinical applications, drug resistance mechanisms, and co-administration of cefiderocol.
Subject(s)
Cefiderocol , Gram-Negative Bacterial Infections , Humans , Siderophores/pharmacology , Siderophores/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cephalosporins/pharmacology , Cephalosporins/therapeutic use , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacteria , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity TestsABSTRACT
It is a common practice to provide fast-growing broilers with high-fat diets in the context of integrated farms in Northeast China. Therefore, fat digestion, absorption, and utilization efficiency are critical for broiler meat production. Bile acids (BA) promote fat digestion and absorption, but whether and how BA affects muscle growth in broilers remains unclear. In this study, 1-day-old broilers were fed diets containing varying levels of crude fat (low, medium, and high) with or without BA supplementation for 42 d. Chickens fed a high-fat diet supplemented with BA exhibited significantly (P < 0.05) higher body weight (BW) at 21 d and average daily gain (ADG) during the first 21 d compared to the other groups. Throughout the entire experiment, feed conversion rate (FCR) was significantly (P < 0.05) lower in the high-fat group without the addition of BA, which was further decreased (P < 0.05) with BA supplementation. The improved growth performance in the BA-supplemented high-fat group was associated with significantly (P < 0.05) higher lipase activity in the small intestine chyme, a decreased trend (P = 0.06) in abdominal fat ratio, and significantly (P < 0.05) higher breast muscle mass. Histological analysis revealed significant (P < 0.05) increases in myofiber diameter, cross-sectional area, and RNA and DNA concentrations in the breast muscle of BA-supplemented broilers on the high-fat diet. Additional histological analysis further revealed significant (P < 0.05) enhancements in myofiber diameter, cross-sectional area, and RNA and DNA concentrations within the breast muscles of broilers supplemented with BA and a high-fat diet. The increased insulin-like growth factor 2 (IGF2) in the breast muscle of broilers fed a BA-supplemented high-fat diet correlated with significantly (P < 0.05) increased farnesoid X factor (FXR) protein expression and binding to the IGF2 promoter. These results suggest that dietary BA supplementation improves FCR and breast muscle growth in broilers fed a high-fat diet, potentially through the FXR-mediated IGF2 pathway.
Subject(s)
Bile Acids and Salts , Chickens , Animals , Chickens/physiology , Diet/veterinary , Dietary Supplements/analysis , Diet, High-Fat , Pectoralis Muscles , DNA , RNA , Animal Feed/analysis , Animal Nutritional Physiological PhenomenaABSTRACT
In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.
Subject(s)
Diterpenes , Rubus , Rubus/chemistry , Molecular Structure , Glycosides/pharmacology , Glycosides/chemistry , Cyclic Nucleotide Phosphodiesterases, Type 5 , Diterpenes/pharmacologyABSTRACT
Although numerous studies highlight the health benefits of tea, excessive consumption has been linked to toxic conditions. Thus, understanding the optimal consumption of tea is essential to minimize toxicity while maximizing its benefits. In this study, we investigated the effects of eight green tea samples (G1-G8) and eight black tea samples (R1-R8) from Camellia sinensis, the most popular teas in Asian culture, on RSC96 Schwann neural cells and embryonic cardiomyocyte H9c2 cells. The results showed that the IC50 (mg/ml, weight/volume) of both tea types were inversely proportional to their polyphenol content, suggesting a relationship between toxicity and polyphenol levels in both green and black tea. Interestingly, green teas generally have higher polyphenol content than black teas. We also assessed the protective effects of tea in vitro by pretreating cells with the teas at indicated doses of polyphenol and subsequently exposing them to H2O2. Both tea types significantly reduced the decline in cell viability for both cell lines, and there was no significant difference in protective polyphenol concentrations for green (G3 & G7) and black (R3 & R8) teas at effective concentrations (EC20 and EC40). To evaluate the preventative effects of tea in vivo, we examined the impact of two green (G3 & G7) and two black (R3 & R8) teas with varying polyphenol content on dextran sulfate sodium (DSS)-induced inflammatory colitis in mice. Tea-treated groups exhibited significantly lower inflammatory scores (DAI) than the control group. DSS treatment in the control group led to shortened colorectal lengths in mice, while tea co-treatment partially prevented this loss. Histological analysis revealed that G7 and R3 (with a moderate polyphenol content) treatment improved colorectal crypt structure, decreased the severity of inflammatory ulcerative colitis, and significantly reduced histological scores compared to the control group. However, G3 and R8 (with high and low doses of polyphenol content, respectively) did not show these effects, suggesting that a moderate polyphenol level in both tea types is optimal for preventative benefits.
Subject(s)
Camellia sinensis , Colorectal Neoplasms , Animals , Mice , Polyphenols/pharmacology , Polyphenols/therapeutic use , Tea/adverse effects , Tea/chemistry , Hydrogen Peroxide , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/chemistry , Camellia sinensis/chemistry , Colorectal Neoplasms/chemically inducedABSTRACT
Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.