Long noncoding RNA UCA1 promotes the chondrogenic differentiation of human bone marrow mesenchymal stem cells via regulating PARP1 ubiquitination.

Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) UCA1 has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms in these processes. the expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminishes the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.

Tryptophan metabolism and piglet diarrhea: Where we stand and the challenges ahead.

The intestinal architecture of piglets is vulnerable to disruption during weaning transition and leads to diarrhea, frequently accompanied by inflammation and metabolic disturbances (including amino acid metabolism). Tryptophan (Trp) plays an essential role in orchestrating intestinal immune tolerance through its metabolism via the kynurenine, 5-hydroxytryptamine, or indole pathways, which could be dictated by the gut microbiota either directly or indirectly. Emerging evidence suggests a strong association between piglet diarrhea and Trp metabolism. Here we aim to summarize the intricate balance of microbiota-host crosstalk by analyzing alterations in both the host and microbial pathways of Trp and discuss how Trp metabolism may affect piglet diarrhea. Overall, this review could provide valuable insights to explore effective strategies for managing piglet diarrhea and the related challenges.

A Prospective Self-controlled Clinical Trial of Nonactivated Low Leukocyte PRP in Female Pattern Hair Loss Patients of Childbearing Age.

BACKGROUND: Alopecia significantly affects the mental health and social relationship of women since childbearing age, highlighting the need for a safe, effective, and convenient treatment. METHODS: The authors have conducted a prospective self-controlled trial involving 15 female patients at childbearing age with alopecia. These patients received a subcutaneous scalp injection of platelet-rich plasma once every 4 weeks for 3 treatments in total. Outcome measurements were included below: changes in hair density (hair/cm2), hair follicle density (hair follicle/cm2), and overall photographic assessment (improved or not) at 4, 12, and 24 weeks right after the first treatment. RESULTS: Comparing the photographs taken before and after the intervention, 67% of patients' hair density increased from 151 ± 39.82 hairs/cm2 (preintervention) to 170.96 ± 37.14 hairs/cm2 (at 24-week follow-up), representing an approximate increase of 19 hairs/cm2. Meanwhile, hair follicle density increased by approximately 15 follicles/cm2 after 24 weeks since the first treatment, rising from 151.04 ± 41.99 follicles/cm2 to 166.72 ± 37.13 follicles/cm2. The primary adverse reactions observed were local swelling and pain due to injections. CONCLUSION: Local injection of nonactivated platelet-rich plasma with low leukocytes concentration could be an effective strategy to alleviate alopecia symptoms in female patients.

Nutrition strategies to control post-weaning diarrhea of piglets: From the perspective of feeds.

Post-weaning diarrhea (PWD) is a globally significant threat to the swine industry. Historically, antibiotics as well as high doses of zinc oxide and copper sulfate have been commonly used to control PWD. However, the development of bacterial resistance and environmental pollution have created an interest in alternative strategies. In recent years, the research surrounding these alternative strategies and the mechanisms of piglet diarrhea has been continually updated. Mechanically, diarrhea in piglets is a result of an imbalance in intestinal fluid and electrolyte absorption and secretion. In general, enterotoxigenic Escherichia coli (ETEC) and diarrheal viruses are known to cause an imbalance in the absorption and secretion of intestinal fluids and electrolytes in piglets, resulting in diarrhea when Cl- secretion-driven fluid secretion surpasses absorptive capacity. From a perspective of feedstuffs, factors that contribute to imbalances in fluid absorption and secretion in the intestines of weaned piglets include high levels of crude protein (CP), stimulation by certain antigenic proteins, high acid-binding capacity (ABC), and contamination with deoxynivalenol (DON) in the diet. In response, efforts to reduce CP levels in diets, select feedstuffs with lower ABC values, and process feedstuffs using physical, chemical, and biological approaches are important strategies for alleviating PWD in piglets. Additionally, the diet supplementation with additives such as vitamins and natural products can also play a role in reducing the diarrhea incidence in weaned piglets. Here, we examine the mechanisms of absorption and secretion of intestinal fluids and electrolytes in piglets, summarize nutritional strategies to control PWD in piglets from the perspective of feeds, and provide new insights towards future research directions.

Isocaloric diets with varying protein levels affected energy metabolism in young adult Sprague-Dawley rats via modifying the gut microbes: A lipid imbalance was brought on by a diet with a particularly high protein content.

Protein is the most important macro-nutrient when it comes to maximizing health, body composition, muscle growth, and recovery of body tissue. In recent years, it has been found that protein also plays an important role in metabolism and gut microbiota. This study was performed to investigate the effects of an isocaloric diet with different crude protein contents on the energy metabolism of Sprague-Dawley (SD) rats. Results revealed that compared with the 20% crude protein (CP; control) diet, the 38% CP diet improved serum parameters that are associated with dyslipidemia and glucose metabolic disorders in SD rats, whereas the 50% CP diet increased liver injury indicators and fatty acid synthesis-related genes and protein expression in the liver. Compared with the control diet, the 14% CP diet increased the abundance of colonic short-chain fatty acid-producing bacteria (Lachnospiraceae_NK4A136_group and Ruminiclostridium_9) and promoted colonic microbial cysteine and methionine metabolism, the 38% CP diet up-regulated colonic microbial lysine biosynthesis and degradation pathways, and the 50% CP diet down-regulated colonic mucosal cholesterol metabolism. Furthermore, the increase of multiple colonic enteropathogenic bacteria in the 50% CP group was associated with higher palmitic acid and stearic acid concentrations in the colonic microbes and lower cholesterol and arachidonic acid concentrations in the colonic mucosa. These findings revealed that the 14% CP and 38% CP diets improved rats' energy metabolism, while the 50% CP diet was accompanied by lipid metabolism imbalances and an increase in the abundance of multiple enteropathogenic bacteria.

Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Effect of Low Protein Diets Supplemented with Sodium Butyrate, Medium-Chain Fatty Acids, or n-3 Polyunsaturated Fatty Acids on the Growth Performance, Immune Function, and Microbiome of Weaned Piglets.

This study aimed to investigate the effects of low-protein (LP) diets supplemented with sodium butyrate (SB), medium-chain fatty acids (MCT), or n-3 polyunsaturated fatty acids (n-3 PUFA) on the growth performance, immune function, and the microbiome of weaned piglets. A total of 120 healthy weaned piglets ((Landrace × Large White × Duroc); 7.93 ± 0.7 kg initial body weight), were randomly divided into five groups. Each group consisted of six replications with four piglets per replication. Dietary treatments included control diet (CON); LP diet (LP); LP + 0.2% SB diet (LP + SB); LP + 0.2% MCT diet (LP + MCT); and LP + PUFA diet (LP + PUFA). The experimental period lasted for 4 weeks. Compared with the CON diet, LP, LP + SB, LP + MCT, and LP + PUFA diets decreased the final weight and average daily gain (ADG) of piglets (p < 0.05). There were lower (p < 0.05) concentrations of IL-8 and higher (p < 0.05) Glutathione peroxidase (GSH-Px) activity in the plasma of piglets fed with LP + SB, LP + MCT, and LP + PUFA diets than those fed with the LP diet. The piglets in the LP + SB and LP + PUFA groups had lower IKK-alpha (IKKa) mRNA expression in the colonic mucosa compared with those in the CON and LP groups (p < 0.05). The mRNA expression of TLR4 in the colonic mucosa of piglets in the LP + SB, LP + MCT, and LP + PUFA groups was decreased when compared with the CON and LP groups (p < 0.05). The LP + MCT diets increased the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosa of piglets compared with CON, LP, and LP + SB diets (p < 0.05). The abundance of Erysipelotrichaceae in the colonic microbiome of piglets in the LP group was higher than that in the other four groups (p < 0.05). Collectively, this study showed that LP diets supplemented with SB, MCT, or n-3 PUFA reduced plasma inflammatory factor levels, increased plasma GSH-Px activity, and declined mRNA expression of TLR4 and IKKa in the colonic epithelium, whereas it reduced the abundance of Erysipelotrichaceae in the colon of piglets.

Potential therapeutic effects of milk-derived exosomes on intestinal diseases.

Exosomes are extracellular vesicles with the diameter of 30 ~ 150 nm, and are widely involved in intercellular communication, disease diagnosis and drug delivery carriers for targeted disease therapy. Therapeutic application of exosomes as drug carriers is limited due to the lack of sources and methods for obtaining adequate exosomes. Milk contains abundant exosomes, several studies have shown that milk-derived exosomes play crucial roles in preventing and treating intestinal diseases. In this review, we summarized the biogenesis, secretion and structure, current novel methods used for the extraction and identification of exosomes, as well as discussed the role of milk-derived exosomes in treating intestinal diseases, such as inflammatory bowel disease, necrotizing enterocolitis, colorectal cancer, and intestinal ischemia and reperfusion injury by regulating intestinal immune homeostasis, restoring gut microbiota composition and improving intestinal structure and integrity, alleviating conditions such as oxidative stress, cell apoptosis and inflammation, and reducing mitochondrial reactive oxygen species (ROS) and lysosome accumulation in both humans and animals. In addition, we discussed future prospects for the standardization of milk exosome production platform to obtain higher concentration and purity, and complete exosomes derived from milk. Several in vivo clinical studies are needed to establish milk-derived exosomes as an effective and efficient drug delivery system, and promote its application in the treatment of various diseases in both humans and animals.

Supplementation with Antimicrobial Peptides or a Tannic Acid Can Effectively Replace the Pharmacological Effects of Zinc Oxide in the Early Stages of Weaning Piglets.

Zinc oxide (ZnO) harms the environment and can potentially increase the number of drug-resistant bacteria. Therefore, there is an urgent need to find safe and effective alternatives to improve gut health and reduce the incidence of diarrhea in weaned piglets. This study conducted an antibacterial test of ZnO, antibacterial peptides (AMPs), and tannic acid (TA) in vitro. Thirty piglets were randomly allotted to one of the following three dietary treatments: ZnO (2000 mg/kg ZnO diet), AMPs (700 mg/kg AMPs diet), and TA (1000 mg/kg TA diet). The results showed that the minimum inhibitory concentrations of ZnO and TA against Escherichia coli and Salmonella were lower than those of AMPs, and the minimum inhibitory concentrations of ZnO, AMPs, and TA against Staphylococcus aureus were the same. Compared to ZnO, AMPs increased the digestibility of dry, organic matter and the crude fat. Additionally, TA significantly (p < 0.05) increased the digestibility of dry and organic matter. On experimental day 14, the plasma interleukin-6 (IL-6) content of piglets supplemented with AMPs and TA was increased significantly (p < 0.05). On experimental day 28, alanine aminotransferase activity in the plasma of weaned piglets in the ZnO and TA groups was significantly (p < 0.05) higher than in piglets in the AMPs group. The levels of plasma IL-6 and immunoglobulin M (IgM) were significantly higher (p < 0.05) in the ZnO and AMPs groups than in the TA group. On experimental days 14 and 28, no significant differences were observed in the antioxidant capacity among the three experimental groups. Intestinal microbial diversity analysis showed that the Chao1 and ACE indices of piglets in the AMPs group were significantly higher (p < 0.05) than those in the ZnO and TA groups. At the genus level, the relative abundance of Treponema_2 was higher in the feces of piglets fed a diet supplemented with TA than in those fed diet supplemented with ZnO (p < 0.05). The relative abundance of Lachnospiraceae was higher in the feces of piglets fed a diet supplemented with AMPs than in those fed diet supplemented with ZnO or TA. Overall, AMPs and TA could be added to feed as substitutes for ZnO to reduce diarrhea, improve nutrient digestibility and immunity, and increase the abundance of beneficial intestinal bacteria in weaned piglets.

Effects of maternal high-fat diet on fetal growth, placental nutrient transporters and circular RNA expression profiles.

Epidemiological and experimental studies suggest that there is a strong correlation between maternal high-fat diet and fetal-placental development. The current study aims to investigate the effects of maternal high-fat diet on fetal growth, placental nutrient transporters and circular RNA expression profiles in a mouse model. Forty C57BL/6 female mice were randomly assigned to two groups, fed either a control (10% fat for energy) diet (CON) or a high-fat (60% fat for energy) diet (HFD) for 4 weeks before mating and throughout pregnancy, and were killed on day 19.5 of pregnancy. The serum glucose, total cholesterol and low-density lipoprotein, the glucolipid metabolism-related hormones, and the insulin resistance index were significantly increased. High-throughput sequencing showed that differentially expressed circRNAs (DE circRNAs) in the placenta can regulate various biological processes, cellular components, and molecular functions through various energy metabolism pathways, and mmu-let-7g-5p was found to target and bind to multiple DE circRNAs. In addition, this study also predicted that various circRNAs with protein coding functions can regulate maternal placental nutrient transport. In general, the ceRNA (circRNAs-miRNAs-mRNAs) regulatory network of maternal placental nutrient transport constructed in this study is of great significance for further understanding the effect of maternal nutrition on fetal growth in the future.

Different Fatty Acid Supplementation in Low-Protein Diets Regulate Nutrient Utilization and Lipid and Amino Acid Metabolism in Weaned Pigs Model.

This study was conducted to evaluate the effects of a low-protein (LP) diet supplemented with sodium butyrate (SB), medium-chain fatty acids (MCFAs) and n-3 polyunsaturated fatty acids (PUFAs) on nutrient utilization and lipid and amino acid metabolism in weaned pigs. A total of 120 Duroc × Landrace × Yorkshire pigs (initial body weight: 7.93 ± 0.65 kg) were randomly assigned to five dietary treatments, including the control diet (CON), LP diet, LP + 0.2% SB diet (LP + SB), LP + 0.2% MCFA diet (LP + MCFA) and LP + 0.2% n-3 PUFA diet (LP + PUFA). The results show that the LP + MCFA diet increased (p < 0.05) the digestibility of dry matter and total P in pigs compared with the CON and LP diets. In the liver of the pigs, the metabolites involved in sugar metabolism and oxidative phosphorylation significantly changed with the LP diet compared with the CON diet. Compared with the LP diet, the altered metabolites in the liver of the pigs fed with the LP + SB diet were mainly associated with sugar metabolism and pyrimidine metabolism; the altered metabolites in the liver of pigs fed with the LP + MCFA and LP + PUFA diets were mainly associated with lipid metabolism and amino acid metabolism. In addition, the LP + PUFA diet increased (p < 0.05) the concentration of glutamate dehydrogenase in the liver of pigs compared with the LP diet. Furthermore, the LP + MCFA and LP + PUFA diets increased (p < 0.05) the mRNA abundance of sterol regulatory element-binding protein 1 and acetyl-CoA carboxylase in the liver compared with the CON diet. The LP + PUFA diet increased (p < 0.05) mRNA abundances of fatty acid synthase in the liver compared with the CON and LP diets. Collectively, the LP diet supplemented with MCFAs improved nutrient digestibility, and the LP diet supplemented with MCFAs and n-3 PUFAs promoted lipid and amino acid metabolisms.

Immunomodulatory Effect of Isocaloric Diets with Different Protein Contents on Young Adult Sprague Dawley Rats.

To understand the potential mechanisms of dietary protein on intestinal and host health, we studied the immunomodulatory effects of isocaloric diets with high or low crude protein (CP) contents on young adult Sprague Dawley (SD) rats. A total of 180 healthy male rats were randomly assigned to six groups (six replicate pens per treatment with five rats per pen) and fed diets with 10% CP, 14% CP, 20% CP (control), 28% CP, 38% CP, and 50% CP. Compared with the control diet, the rats fed the 14% CP diet significantly elevated lymphocyte cell counts in the peripheral blood and ileum, whereas the 38% CP diet significantly activated the expression of the TLR4/NF-κB signaling pathway in the colonic mucosa (p < 0.05). Moreover, the 50% CP diet reduced growth performance and fat deposition and increased the percentages of CD4+ T, B, and NK cells in the peripheral blood and the colonic mucosal expression of IL-8, TNF-α, and TGF-ß. Overall, rats fed the 14% CP diet enhanced host immunity by increasing the numbers of immune cells, and the immunological state and growth of SD rats were negatively impacted by the diet containing 50% CP.

Effects of Different Combinations of Sodium Butyrate, Medium-Chain Fatty Acids and Omega-3 Polyunsaturated Fatty Acids on the Reproductive Performance of Sows and Biochemical Parameters, Oxidative Status and Intestinal Health of Their Offspring.

The aim of the study was to investigate the comparative effects of different combinations of sodium butyrate (SB), medium-chain fatty acids (MCFAs), and omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the reproductive performances of sows, as well as on the biochemical parameters, oxidative statuses, and intestinal health of the sucking piglets. A total of 30 sows were randomly allocated to five treatments: (1) control diet (CON); (2) CON with 1 g/kg of coated SB and 7.75 g/kg of coated MCFAs (SM); (3) CON with 1 g/kg of coated SB and 68.2 g/kg of coated n-3 PUFAs (SP); (4) CON with 7.75 g/kg of coated MCFAs and 68.2 g/kg of coated n-3 PUFAs (MP); (5) CON with 1 g/kg of coated SB, 7.75 g/kg of coated MCFAs and 68.2 g/kg of coated n-3 PUFA (SMP). The results showed that sows fed the SP, MP, and SMP diets had shorter weaning-to-estrus intervals than those fed the CON diet (p < 0.01). The piglets in the SM, SP, and MP groups showed higher increases in the plasma catalase and glutathione peroxidase activities than those of the CON group (p < 0.01). The diarrhea incidence of piglets in the SM, SP and SMP groups was lower than that of piglets in the CON group (p < 0.01). Additionally, the addition of SM, SP, MP, and SMP to the sow diets increased the contents of immunoglobulin A, immunoglobulin G, fat, and proteins in the colostrum (p < 0.01), as well as the plasma total superoxide dismutase activities (p < 0.01) in the suckling piglets, whereas it decreased the mRNA expressions of tumor necrosis factor-α, interleukin-1ß, and toll-like receptor 4 in the jejunum mucosa of the piglets. The relative abundances of Prevotella, Coprococcus, and Blautia in the colonic digesta of the piglets were increased in the SM group (p < 0.05), and the relative abundances of Faecalibacterium increased in the SMP group (p < 0.05), compared with the CON group. The relative abundances of Collinsella, Blautia, and Bulleidia in the MP group were higher than those in the CON group (p < 0.05). Collectively, dietary combinations of fatty acids with different chain lengths have positive effects on the growth performances and intestinal health of suckling piglets.

Whether preferences of gastric cancer patients after surgery for follow-up change over time? Analysis based on discrete choice experiment.

PURPOSES: The purposes of this discrete choice experiment are as follows: (1) quantify the relevant characteristics that may affect the follow-up selection of gastric cancer patients after surgery and (2) explore the differences in follow-up preferences of gastric cancer patients at different stages and reveal the change trend of preferences over time, thereby providing references for the formulation and optimization of follow-up strategies. METHODS: A survey instrument that was developed using the design principle of a discrete choice experiment investigated gastric cancer patients on the day of discharge, and at 3 months, 6 months, and 12 months after discharge. In Stata 15.0, a mixed logit model was used to explore the preferences of gastric cancer patients after surgery at different stages, the willingness to pay was calculated, and the NLCOM command was used to simulate the follow-up uptake rates of different attribute levels at different stages. RESULTS: On the day of discharge, and 3 months, 6 months, and 12 months after discharge, the most important attribute levels of gastric cancer patients after surgery were "thoroughness-very thorough," "method-face-to-face," "thoroughness-very thorough," and "provider-specialist nurse," respectively, and patients were willing to pay more for these services. Patients' preference for the attribute level "very thorough" decreased over time, while their preferences for "specialist doctors" as follow-up providers remained relatively stable. Furthermore, the attribute levels with the greatest effect on receiving the baseline follow-up program varied across stages. CONCLUSION: The gastric cancer patients' preferences for follow-up change over time, and the time factor should be considered when developing follow-up strategies.

Detection of pathogenic variants in four patients with globozoospermia / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for 4 patients with globozoospermia.@*METHODS@#Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.@*RESULTS@#All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region.@*CONCLUSION@#DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.

Gut microbiota: a new insight into neurological diseases / 中华医学杂志(英文版)

In the last decade, it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host. Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases, e.g., Parkinson's disease, Alzheimer's disease, and myasthenia gravis. However, the underlying molecular mechanisms are complex and remain unclear. Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation, indicating that the gut microbiota may be an important regulator of neurological diseases. However, further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases. Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders. In this review, we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases, and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.

Cangxi Tongbi Capsules promote chondrocyte autophagy by regulating circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit development of knee osteoarthritis / 中国中药杂志

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1β(IL-1β) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1β showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.

Effects of dietary supplementation with essential oils and protease on growth performance, antioxidation, inflammation and intestinal function of weaned pigs.

This experiment evaluated the impacts of essential oils (EO) and protease (PRO), independently or in combination, on growth performance, antioxidation, inflammation and intestinal function of weaned pigs. One hundred and sixty weaned pigs (21 d of age, BW of 6.74 ± 0.20 kg) were randomly divided into 4 treatments with 8 replicate pens of 5 pigs per pen. Dietary treatments included the following: 1) control diet (CON), 2) CON with 300 mg/kg essential oils (EO), 3) CON with 500 mg/kg protease (PRO), 4) CON with 300 mg/kg essential oil and 500 mg/kg protease (EO + PRO). On d 8, one pig from each pen was selected for sampling. The remaining pigs were fed for an additional week and growth performance was monitored during this period. Dietary treatments had no marked effects (P > 0.05) on the growth performance of pigs. However, pigs receiving EO diet had higher (P < 0.05) serum glutathione peroxidase (GSH-Px) activity, and tended to decrease (P = 0.063) serum concentration of tumor necrosis factor-α (TNF-α). In addition, pigs receiving EO diet had higher (P < 0.05) abundances of phylum Actinobacteria, and genera Bifidobacterium, and lower (P < 0.05) phylum Bacteroidetes and genera Alloprevotella in colonic digesta. Pigs receiving PRO diet decreased (P < 0.05) the serum concentration of malondialdehyde (MDA) and diamine oxidase activity, increased (P < 0.05) the villus height and the ratio of villus height to crypt depth in duodenum, increased sucrase activity in jejunal mucosa, and also increased the abundance of phylum Actinobacteria in colonic digesta. Furthermore, the synergistic effects of EO and PRO was observed (P < 0.05) for pigs with decreasing serum TNF-α concentration and increasing serum GSH-Px activity. Collectively, the results indicated that dietary supplementation of EO and PRO had no significant effects on growth performance of weaned pigs. EO diet appeared to improve antioxidant activity and intestinal microbiota, while PRO diet improved intestinal morphology and digestive enzyme activity, and there was a synergistic effect of EO and PRO on reducing inflammatory parameters in weaned pigs.

Long-term maternal intake of inulin exacerbated the intestinal damage and inflammation of offspring rats in a DSS-induced colitis model.

This study aimed to investigate the effects of long-term maternal intake of inulin on intestinal morphology, permeability, inflammation and microbiota of offspring rats treated with dextran sulfate sodium (DSS). Sixteen female adult Sprague-Dawley rats were assigned to two groups receiving the fiber-free diet (FFD) or inulin diet (INU, 5% inulin) for three parities. The offspring weaned rats (third-parity) were fed with the same diet for four weeks until receiving 6% DSS for 7 days; the four groups were as follows: FFD, FFD + DSS, INU and INU + DSS. The results showed that maternal intake of inulin increased the histopathology score and activity of diamine oxidase (DAO) in serum, and the highest histopathology scores and activity of DAO were observed in INU + DSS rats. Maternal intake of inulin increased the activity of myeloperoxidase (MPO), mRNA expressions of inflammatory factors and protein expression of IL-1ß in colonic tissues. Likewise, INU + DSS rats had the highest activity of MPO and mRNA expressions of inflammatory factors in colonic tissues. Maternal intake of inulin increased the abundances of Bacteroidetes, Bacteroides and Parasutterella, which were the highest enriched in INU + DSS rats. The level of acetate in the colonic digesta of INU + DSS rats was lower than that in FFD and INU rats. These results indicated that long-term maternal intake of inulin exacerbated the intestinal damage and inflammation of DSS-induced offspring rats, associated with the decreased level of acetate and altered intestinal microbiota.

Maternal Long-Term Intake of Inulin Improves Fetal Development through Gut Microbiota and Related Metabolites in a Rat Model.

Adequate dietary fiber intake during gestation is critical for maternal-fetal health. This experiment aims to uncover the impacts of maternal long-term intake of inulin on fetal development and its underlying mechanism. Eighty female Sprague-Dawley rats were randomly assigned to two groups receiving either a fiber-free diet or an inulin diet (inulin) for three parities. On the 19th day of pregnancy in the third parity, blood, intestinal, placental, and colonic digesta samples were collected. Results showed that maternal intake of inulin significantly decreased the within-litter birth weight variation in parities 2 and 3. Inulin intake modified the gut microbiome profiles and elevated the colonic contents of short chain fatty acids (propionate and butyrate). Inulin decreased the serotonin (5-HT) concentration in the colon, whereas it increased the 5-HT concentrations in serum and placenta and the number of 5-HT+ enterochromaffin cells in the colon. The protein expression of melatonin-synthesizing enzyme (arylalkylamine N-acetyltransferase) and the melatonin concentration in the placenta were also increased by inulin. Inulin improved the placental redox status and nutrient transport. These findings indicated that maternal long-term intake of inulin improves fetal development by altering the intestinal microbiota and related metabolites in rats.