Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma: a mediation Mendelian randomization study.

OBJECTIVE: This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations. METHODS: We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP). Next, we quantified the proportion of mediation effects by multivariable Mendelian randomization (MVMR). Last, we performed reverse MR analyses. Sensitivity analyses were conducted to enhance the robustness of our findings. RESULTS: Only coffee intake demonstrated a significant negative casual effect on gout (inverse variance weighted: OR = 0.444, p = 0.049). In two-step MR, coffee intake decreased urate and urea while increased SHBG levels, but did not affect IL-18 and CRP levels. Besides, urate and urea showed positive causal effects while SHBG exhibited a negative impact on gout. In mediation analysis, urate, urea, and SHBG respectively mediated 53.60%, 16.43%, and 4.81% of the total causal effect of coffee intake on gout. The three mediators collectively mediated 27.45% of the total effect. Reverse MR analyses suggested no significant reverse causal effects. Sensitivity analyses supported the reliability of our causal inferences. CONCLUSION: Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma. These findings accentuate the benefits of coffee intake for gout management. The mediators may provide a novel insight into potential therapeutic targets for gout prevention. Key Points • This study determines the causally protective effect of coffee intake on gout. • We reveal that coffee intake reduced the risk of gout by decreasing urate and urea while increasing SHBG levels in plasma. • Identifying specific mediators in the causal pathway from coffee intake to gout provides valuable information for clinical interventions of gout.

Evaluation on the Potential for Hepatotoxic Components from Herba Epimedii to Induce Apoptosis in HepG2 Cells and the Analysis of the Influence of Metabolism in Liver Microsomes.

The potential hepatotoxicity of Herba Epimedii is a focal point in traditional Chinese medicine security applications. As determined in our previous study, the flavonoid constituents of Herba Epimedii, sagittatoside A, icariside I, baohuoside I and icaritin, are related to the hepatotoxicity of this herb. However, the hepatotoxic mechanism of these components needs to be clarified further, and whether these components can maintain their injury action following liver metabolism needs to be confirmed. Herein, the effects of sagittatoside A, icariside I, baohuoside I and icaritin on the apoptosis of HepG2 cells and the expression of key proteins, including Bax, Bcl-2, Caspase-3 and Caspase-9, were evaluated. Moreover, with liver microsome incubation, the influences of metabolism on the apoptotic activities of these components were investigated. Then, by HPLC-MS/MS analyses, the in vitro metabolic stability of these components was determined after incubation with different kinds of liver microsomes to explain the reason for the influence. The results suggested that sagittatoside A, baohuoside I and icaritin could induce apoptosis, which is likely to be closely related to the induction of the intrinsic apoptosis pathway. After metabolic incubation, the sagittatoside A and icaritin metabolism mixture could still induce apoptosis due to less metabolic elimination, while the icariside I and baohuoside I metabolism mixtures respectively got and lost the ability to induce apoptosis, probably due to quick metabolism and metabolic transformation. The findings of this study may provide important references to explore the material basis and mechanism of the hepatotoxicity of Herba Epimedii.

Effect of dietary Glycyrrhiza polysaccharides on growth performance, hepatic antioxidant capacity and anti-inflammatory capacity of broiler chickens.

The primary aim of this study was to investigate the impact of varying levels of dietary Glycyrrhiza polysaccharides (GPS) on the health status of broiler chickens. A total of 288 1-day-old Arbor Acres broilers were randomly assigned to four groups with six replicates, consisting of 12 chickens in each replicate. The control group (CON) was provided with the basal diet, while the experimental groups were administered 300, 600, and 900 mg/kg of GPS in the basal diet for 42 days. The results demonstrated a significant enhancement in average daily gain (ADG) as a result of GPS supplementation (P < 0.05). The dietary GPS significantly elevated total antioxidation capability (T-AOC) and the activity of antioxidant enzymes (P < 0.05), while effectively reducing the levels of malondialdehyde (MDA) in the serum and liver (P < 0.05). Administration of GPS notably inhibited the toll-like receptor 4 (TLR4) signaling pathway (P < 0.05), decreased interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) levels (P < 0.05), and increased IL-4 and IL-10 levels (P < 0.05). Additionally, the expression of crucial regulators involved in liver lipid metabolism, including sterol regulatory element binding protein 1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were significantly reduced (P < 0.05). In contrast, the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) was significantly enhanced in the GPS-supplemented groups (P < 0.05). In conclusion, the supplementation of GPS positively influenced the growth performance, the anti-inflammatory and antioxidant capacity of the liver, as well as liver lipid metabolism in broilers.

Design strategies for enhancing antitumor efficacy through tumor microenvironment exploitation using albumin-based nanosystems: A review.

The tumor microenvironment (TME) is a complex and dynamic system that plays a crucial role in regulating cancer progression, treatment response, and the emergence of acquired resistance mechanisms. The TME is usually featured by severe hypoxia, low pH values, high hydrogen peroxide (H2O2) concentrations, and overproduction of glutathione (GSH). The current development of intelligent nanosystems that respond to TME has shown great potential to enhance the efficacy of cancer treatment. As one of the functional macromolecules explored in this field, albumin-based nanocarriers, known for their inherent biocompatibility, serves as a cornerstone for constructing diverse therapeutic platforms. In this paper, we present a comprehensive overview of the latest advancements in the design strategies of albumin nanosystems, aiming to enhance cancer therapy by harnessing various features of solid tumors, including tumor hypoxia, acidic pH, the condensed extracellular matrix (ECM) network, excessive GSH, high glucose levels, and tumor immune microenvironment. Furthermore, we highlight representative designs of albumin-based nanoplatforms by exploiting the TME that enhance a broad range of cancer therapies, such as chemotherapy, phototherapy, radiotherapy, immunotherapy, and other tumor therapies. Finally, we discuss the existing challenges and future prospects in direction of albumin-based nanosystems for the practical applications in advancing enhanced cancer treatments.

Erythrocyte membrane n-3 PUFA are inversely associated with breast cancer risk among Chinese women.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

[Electroacupuncture at acupoints of yangming meridians for sarcopenia: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of electroacupuncture at acupoints of yangming meridians for sarcopenia. METHODS: A total of 60 patients with sarcopenia were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional nutrition intervention for sarcopenia was adopted. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at bilateral Binao (LI 14), Quchi (LI 11), Zusanli (ST 36), Yanglingquan (GB 34), etc.,ipsilateral Quchi (LI 11) and Zusanli (ST 36) were connected to electroacupuncture, with discontinuous wave, 2 Hz in frequency, 1-10 mA in intensity, 2 times a week, with a interval of 3 days. A total of 12-week treatment was required in the two groups. Before and after treatment, the appendicular skeletal muscle mass index (ASMI), grip strength, 6 m-walking time, body fat percentage and body moisture percentage were observed in the two groups. RESULTS: Compared with those before treatment, after treatment, ASMI and grip strength were increased while 6 m-walking time was shortened in the two groups (P<0.05); body fat percentage was decreased while body moisture percentage was increased in the observation group (P<0.05). After treatment, in the observation group, ASMI, grip strength and body moisture percentage were increased (P<0.05), 6 m-walking time was shortened and body fat percentage was decreased (P<0.05) compared with those in the control group. CONCLUSION: Electroacupuncture at acupoints of yangming meridians can effectively improve the skeletal muscle mass, muscle function, body fat percentage and body moisture percentage in patients with sarcopenia, and make the distribution of muscle and fat more reasonable.

Tea polyphenols protect bovine intestinal epithelial cells from the adverse effects of heat-stress in vitro.

Heat-stress (HS) leads to impaired gut health, adversely affecting milk production of dairy cows. In the present study, we investigated the protective effects of tea polyphenols (TP) against HS-induced damage in bovine intestinal epithelial cells (BIECs) and explored the underlying mechanisms. Primary BIECs were isolated from bovine duodenum, cultured and treated as follows: (1) control cells incubated in complete medium at 37 °C for 12 h, (2) TP group incubated in medium containing 100 µg/mL TP at 37 °C for 12 h, (3) HS group incubated in medium at 37 °C for 6 h followed by 6 h at 42 °C, and (4) HS + TP group incubated with 100 µg/mL TP for 6 h at 37 °C and 6 h at 42 °C. TP improved cell viability and antioxidant capacity, and decreased apoptosis and LDH activity. TP led to upregulation of Nrf2 and its target antioxidant genes HO-1, NQO1 and SOD1 expression. TP significantly decreased the expression of proinflammatory cytokine genes (NF-κB, IL-6 and TNF-α), and increased expression of the anti-inflammatory cytokine gene, IL-10. The above results suggested that TP protected BIECs from HS-induced adverse effects by alleviating oxidative stress and inflammatory responses, indicating that TP can alleviate HS-induced intestinal damage in dairy cows.

Reactive Oxygen Species-Triggered Curcumin Release from Hollow Mesoporous Silica Nanoparticles for PM2.5-Induced Acute Lung Injury Treatment.

Exposure to fine particulate matter with a diameter ≤2.5 µm (PM2.5) can result in serious inflammation and oxidative stress in lung tissue. However, there is presently very few effective treatments for PM2.5-induced many pulmonary diseases, such as acute lung injury (ALI). Herein, curcumin-loaded reactive oxygen species (ROS)-responsive hollow mesoporous silica nanoparticles (Cur@HMSN-BSA) are proposed for scavenging the intracellular ROS and suppressing inflammatory responses against PM2.5-induced ALI. The prepared nanoparticles were coated with bovine serum albumin (BSA) via an ROS-sensitive thioketal (TK)-containing linker, in which the TK-containing linker would be cleaved by the excessive amounts of ROS in inflammatory sites to induce the detachment of BSA from the nanoparticles surface and thus triggering release of loaded curcumin. The Cur@HMSN-BSA nanoparticles could be used as ROS scavengers because of their excellent ROS-responsiveness, which were able to efficiently consume high concentrations of intracellular ROS. Furthermore, it was also found that Cur@HMSN-BSA downregulated the secretion of several important pro-inflammatory cytokines and promoted the polarization from M1 phenotypic macrophages to M2 phenotypic macrophages for eliminating PM2.5-induced inflammatory activation. Therefore, this work provided a promising strategy to synergistically scavenge intracellular ROS and suppress the inflammation responses, which may serve as an ideal therapeutic platform for pneumonia treatment.

[Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers].

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, ß-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

Effect of dietary Saccharomyces-derived prebiotic refined functional carbohydrates as antibiotic alternative on growth performance and intestinal health of broiler chickens reared in a commercial farm.

The search for effective in-feed antibiotic alternative is growing due to the global trend to reduce or ban the utilization of antibiotics as growth promotors in poultry diets. This study was processed to assess the effect of dietary refined functional carbohydrates (RFCs) replacing antibiotic growth promoters (AGP) on growth performance, intestinal morphologic structure and microbiota, as well as intestinal immune function and barrier function of broilers reared on a commercial broilers farm. Trials contained 3 treatments with 4 replicate broiler houses, with about 25,000 birds each room. The treatments were control group (CON), RFCs group (CON + 100 mg/kg RFCs), and AGP group (CON + 50 mg/kg bacitracin methylene disalicylate (BMD), respectively. Results showed that RFCs and AGP group significantly increased (P < 0.05) average daily gain (ADG) during d 22 to 45 in contrast to control. Compared with the control and AGP-treated groups, feeding RFCs increased (P < 0.05) jejunal villus height to crypt depth ratio. AGP addition reduced (P < 0.05) the jejunal villi surface area compared to broilers fed control and RFC supplemented diets. Supplementation of RFCs promoted (P < 0.05) the growth of Lactobacillus but inhibited Escherichia coli and Salmonella proliferation compared with the control group. Inclusion of RFCs and BMD enhanced (P < 0.05) antibody titers against avian influenza virus H9 compared with control. RFCs and AGP both down-regulated (P < 0.05) intestinal TLR4 mRNA levels, whereas RFCs tended to up-regulate (P = 0.05) IFN-γ gene expression compared to control. Expression of intestinal tight junction genes was not affected by either AGP or RFCs supplementation. Based on above observation, we suggested that RFCs could replace in-feed antibiotic BMD in broiler diets for reducing intestinal pathogenic bacteria and modulating immunity of broilers.

Total Flavonoids of Rhizoma Drynariae Mitigates Aflatoxin B1-Induced Liver Toxicity in Chickens via Microbiota-Gut-Liver Axis Interaction Mechanisms.

Aflatoxin B1 (AFB1) is a common mycotoxin that widely occurs in feed and has severe hepatotoxic effects both in humans and animals. Total flavonoids of Rhizoma Drynaria (TFRD), a traditional Chinese medicinal herb, have multiple biological activities and potential hepatoprotective activity. This study investigated the protective effects and potential mechanisms of TFRD against AFB1-induced liver injury. The results revealed that supplementation with TFRD markedly lessened broiler intestinal permeability by increasing the expression of intestinal tight junction proteins, as well as correcting the changes in gut microbiota and liver damage induced by AFB1. Metabolomics analysis revealed that the alterations in plasma metabolites, especially taurolithocholic acid, were significantly improved by TFRD treatment in AFB1-exposed chickens. In addition, these metabolites were closely associated with [Ruminococcus], ACC, and GPX1, indicating that AFB1 may cause liver injury by inducing bile acid metabolism involving the microbiota-gut-liver axis. We further found that TFRD treatment markedly suppressed oxidative stress and hepatic lipid deposition, increased plasma glutathione (GSH) concentrations, and reversed hepatic ferroptosis gene expression. Collectively, these findings indicate that ferroptosis might contribute to the hepatotoxicity of AFB1-exposed chickens through the microbiota-gut-liver axis interaction mechanisms; furthermore, TFRD was confirmed as an herbal extract that could potentially antagonize mycotoxins detrimental effects.

Transform commercial magnetic materials into injectable gel for magnetic hyperthermia therapy in vivo.

Magnetic hyperthermia therapy of tumors employing magnetic materials has been greatly developed due to their low invasiveness, high specificity, few side effects and no limitation of tissue penetration depth. However, traditional nanoscale magnetocaloric materials exhibited the disadvantages of low tumor enrichment efficiency, complex preparation process and difficulty in large-scale production. While eddy current loss-based magnetic hyperthermia tumor ablation with metal implants faces shortcomings such as high invasiveness and low selectivity of tumor shape and volume. Herein, we developed injectable magnetic gels by adding commercial magnetic metal or metal oxide powders (CMMPs) into alginate-Ca2+ (ALG-Ca2+) gel through an ultra-simple mixing strategy for magneto-thermal therapy of tumors in vivo. The ALG-Ca2+ gel can not only turn the water-insoluble CMMPs into injectable gel, but also retain the inherent magnetic loss-based heating capacity. Besides, CMMPs in the gels are easily retained at the tumor site after peritumoral injection because of their large size and strong hydrophobicity, which benefits the efficiency and accuracy of the treatment and reduces side effects to the surrounding tissues. The prepared ALG-Ca2+-CMMPs give full play to the inherent magneto-thermal capacity of CMMPs, which possesses super high loading ability (>100 mg magnetic materials/mL), superior large-scale production capability (>1 kg in laboratory synthesis), low cost, satisfactory syringeability and biological safety. Collectively, this study provides a convenient and universal strategy for the construction of magnetocaloric materials for biological applications.

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

Effects of Glycyrrhiza polysaccharide on growth performance, appetite, and hypothalamic inflammation in broilers.

We analyzed the effects of Glycyrrhiza polysaccharide (GCP) on growth performance, appetite, and hypothalamic inflammation-related indexes in broilers. One-day-old male AA broilers were randomly divided into four groups: Control, L-GCP, M-GCP, and H-GCP (0, 300, 600, and 900 mg GCP/kg feed), with six repetition cages for each treatment and 12 broilers in each repeat for a period of 42 days. From day 1 to day 21, the addition of GCP to the diet significantly improved the ADFI and the ADG of broilers, and the mRNA levels of NPY and AgRP were significantly increased while POMC and CART were decreased in the hypothalamus of broilers; GCP also significantly decreased the mRNA levels of IL-1ß, IL-6, TNF-α, TLR-4, MyD88, and NF-κB, and increased the IL-4 and IL-10 in the hypothalamus from day 1 to day 42. The concentrations of appetite-related factors and inflammatory factors in serum were changed in the same fashion. Supplementation with 600 mg/kg GCP had the optimal effect in broilers, and GCP has the potential to be used as a feed additive in the poultry production industry.

In this work, we analyzed the effects of Glycyrrhiza polysaccharide on growth performance, appetite, and hypothalamic inflammation in broilers. In the past, antibiotics were added to poultry feed to prevent disease and improve growth performance; however, the extensive use of antibiotics can negatively affect livestock and poultry, and endanger the health of consumers. Glycyrrhiza polysaccharide has many biological activities. In order to explore the possibility of Glycyrrhiza polysaccharide as a substitute for antibiotics, we evaluated the effects of Glycyrrhiza polysaccharide added to the diet of broilers for 42 days. Our research confirmed that Glycyrrhiza polysaccharide supplementation increased food intake by regulating appetite-related factors in hypothalamus and serum, and also alleviated inflammation.

Effects of dietary Glycyrrhiza polysaccharide on growth performance, blood parameters and immunity in weaned piglets.

The purpose of this study was to evaluate the effects of dietary Glycyrrhiza polysaccharide (GCP) on growth performance, blood parameters and immunity in weaned piglets. A total of 240 (10.33 ± 0.62 kg body weight) 35-day-old (Duroc × Landrace × White) weaned piglets were randomly assigned to four dietary treatments, with six replicate pens per treatment and 10 piglets per pen (five males and five females). The dietary treatments continued for 21 days and comprised a basal diet supplemented with 0 (control group), 500, 1000 and 2000 mg/kg GCP. The results showed that the inclusion of 1000 and 2000 mg/kg GCP increased the average daily gain and decreased the feed conversion rate compared with the control group (p < 0.05). The piglets treated with 500 and 1000 mg/kg GCP had a lower diarrhoeal incidence than the control group (p < 0.05). Moreover, supplementation with 1000 mg/kg GCP increased the counts of white blood cells, neutrophils, red blood cells, and platelets, and elevated alkaline phosphatase, total protein, globulin, glucose, triglyceride, immunoglobulin A, immunoglobulin G, and total antioxidant capacity levels (p < 0.05), and decreased malondialdehyde content compare with the control group (p < 0.05). In addition, relative to the control group, piglets fed 500 and 1000 mg/kg GCP had significantly lower expression of interleukin-6 mRNA in spleen (p < 0.05). Our results indicate that dietary supplementation with GCP can improve growth performance, blood parameters and immunity in weaned piglets. Our study suggests that adding 1000 mg/kg GCP to the diet had the most beneficial effect.

Effects of dietary Glycyrrhiza polysaccharide supplementation on growth performance, intestinal antioxidants, immunity and microbiota in weaned piglets.

The aim of this study was to evaluate the effects of dietary Glycyrrhiza polysaccharide (GCP) supplementation on growth performance, intestinal antioxidants, immunity and microbiota in weaned piglets. One hundred and twenty 28-day-old weaned piglets were randomly assigned into five groups (four replicates per group) and fed a basal diet with GCP at 0, 500, 1000, 2000 and 4000 mg/kg for four weeks, respectively. Results showed that 1000 mg/kg GCP improved piglets' ADG and ADFI and reduced FCR (p < .05). Thus, the 0 and 1000 mg/kg GCP dose were selected for subsequent experiments. We found that 1000 mg/GCP increased SOD and T-AOC and decreased MDA in the jejunal mucosa (p < .05). Dietary 1000 mg/kg GCP also resulted in high levels of sIgA, IL-10 and TGF-ß, whereas IL-2 dropped dramatically (p < .05). The relative expression levels of ZO-1, CLDN, OCLDN, TLR-4, IL-10, TGF-ß, Nrf-2, SOD1 and CAT increased in the jejunal mucosa, whereas INF-γ decreased (p < .05). 1000 mg/kg GCP treatment altered the diversity and community composition of cecal microbiota in pigs, with increasing relative abundance of Bacteroidota and Lactobacillus at phylum and genus levels (p < .05), respectively. The results suggested that dietary 1000 mg/kg GCP could improve growth performance and intestinal health of weaned piglets.

Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen-induced metabolic activation and hepatotoxicity.

Psoralen and isopsoralen are the pharmacologically important but hepatotoxic components in Psoraleae Fructus. The purpose of this study was to reveal the underlying mechanism of psoralen/isopsoralen-induced hepatotoxicity. Initially, we applied integrated analyses of transcriptomic and metabolomic profiles in mice treated with psoralen and isopsoralen, highlighting the xenobiotic metabolism by cytochromes P450 as a potential pathway. Then, with verifications of expression levels by qRT-PCR and western blot, affinities by molecular docking, and metabolic contributions by recombinant human CYP450 and mouse liver microsomes, CYP1A2 was screened out as the key metabolic enzyme. Afterwards, CYP1A2 induction and inhibition models in HepG2 cells and mice were established to verify the role of CYP1A2, demonstrating that induction of CYP1A2 aggravated the hepatotoxicity, and conversely inhibition alleviated the hepatotoxic effects. Additionally, we detected glutathione adducts with reactive intermediates of psoralen and isopsoralen generated by CYP1A2 metabolism in biosystems of recombinant human CYP1A2 and mouse liver microsomes, CYP1A2-overexpressed HepG2 cells, mice livers and the chemical reaction system using UPLC-Q-TOF-MS/MS. Ultimately, the high-content screening presented the cellular oxidative stress and relevant hepatotoxicity due to glutathione depletion by reactive intermediates. In brief, our findings illustrated that CYP1A2-mediated metabolic activation is responsible for the psoralen/isopsoralen-induced hepatotoxicity.

Antioxidant monoammonium glycyrrhizinate alleviates damage from oxidative stress in perinatal cows.

This study was conducted to evaluate the antioxidant capability of dietary supplementation with monoammonium glycyrrhizinate (MAG) in perinatal cows. Glycyrrhizic acid has been shown to have strong antioxidant activity and we hypothesised that the aglycone of glycyrrhizin and MAG, could reduce damage from oxidative stress in perinatal cows by enhancing antioxidant capacity. Blood and milk samples were collected from three groups of healthy perinatal cows that were similar in body weight, parity, milk yield in the last milk cycle, etc., receiving dietary MAG supplementation ([Day 0 = parturition]: 0 g/day, [n = 13)] 3 g/day [n = 13] or 6 g/day [n = 11]) from -28 to 56 day (0 day = parturition). Compared with 0 g/day controls (CON), milk fat was significantly decreased in cows fed with MAG, and 3 g/day had the greatest effect. A diet containing 3 g/day MAG decreased the serum alanine aminotransferase (ALT) level compared with CON at -7 day post-partum. ALT was also lower at 5 day post-partum in cows fed with 3 g/day MAG compared to 6 g/day. The administration of 3 g/day and 6 g/day MAG decreased serum aspartate transaminase (AST) at 3 day post-partum. Supplementation of MAG in cows increased total antioxidant capacity (T-AOC) in serum, and cows given 3 g MAG per day had higher T-AOC than controls on post-partum 7 day. At the end of the experiment, we isolated and cultured primary hepatocytes to determine the effect of MAG on oxidative stress caused by incubation with the sodium oleate (SO). SO increased lipid synthesis, but pre-treatment with MAG prevented the fatty buildup. SO treatment increased AST and ALT levels and malondialdehyde concentration, but decreased T-AOC and superoxide dismutase (SOD). Incubation with MAG increased antioxidant capacity and inhibited oxidant damage in bovine hepatocytes. SO stimulated expression of the antioxidant genes, NAD(P)H quinone dehydrogenase 1 (NQO1) and SOD1, in the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, and catalase 1 (CAT1); this increase was accentuated by MAG pre-treatment. The results suggest that MAG can alleviate the damage caused by oxidative stress in perinatal cows by enhancing antioxidant activity.

Effects of dietary Glycyrrhiza polysaccharide on growth, serum biochemistry, immunity, and egg laying in quail.

This study was conducted to evaluate the effects of dietary supplementation with Glycyrrhiza polysaccharide (GCP) on growth performance, serum biochemistry, immunity, and egg laying in female quail. 300 1-day-old female quail were sorted into four dietary treatments with five replicate cages of 15 birds each. The basic diet in the four treatment groups was supplemented with 0, 500, 1000 and 1500 mg/kg GCP, and the experiment continued for 80 days. Results showed that dietary supplementation with GCP significantly (p < 0.05) increased average daily gain in a dose-dependent fashion, and decreased (p < 0.05) the feed-to-gain ratio and mortality. The relative weights of the thymus and bursa of Fabricius increased (p < 0.05) linearly with increasing dose of GCP from 0 to 1500 mg/kg on day 20. GCP birds showed higher serum levels of protein, glucose, immunoglobulin A and immunoglobulin M, but lower serum triglycerides (p < 0.05) on day 50. GCP increased (p < 0.05) average laying rate and average egg weight linearly from days 60 to 80, whereas feed to egg ratio was decreased (p < 0.05). Taken together, these results revealed that GCP could improve growth performance, serum biochemistry, immunity, and egg laying in female quail. Therefore, GCP may be a potential replacement for antibiotic growth promoters in poultry.

Morinda officinalis Polysaccharides Ameliorates Bone Growth by Attenuating Oxidative Stress and Regulating the Gut Microbiota in Thiram-Induced Tibial Dyschondroplasia Chickens.

Tibial dyschondroplasia (TD) occurs in chickens and other fast-growing birds, affecting their cartilage growth and leading to reduced meat quality in broilers. Morinda officinalis polysaccharide (MOP) is one of the chief active components of Morinda officinalis, which promotes bone formation, inhibiting bone loss and having anti-oxidant and anti-inflammatory properties. A total of 120 AA chickens were randomly divided into the CON group (basal diet), TD group (100 mg/kg thiram + basal diet), and MOP group (100 mg/kg thiram + basal diet + water with 500 mg/kg MOP). The experiment lasted 21 days. The results showed that MOP could alleviates broiler lameness caused by TD, restore the morphological structure of tibial growth plate (TGP), increase tibial weight (p < 0.05), balance the disorder of calcium and phosphorus metabolism, and promote bone formation by increasing the expression of BMP-2, Smad4, and Runx2 genes In addition, MOP supplementation stimulated the secretion of plasma antioxidant enzymes (T-SOD and GSH-Px) by regulating the expression of SOD and GPX-1 genes, thereby enhancing the antioxidant capacity of TD broilers. Interestingly, we observed MOP can also improve gut microbiota by increasing the beneficial bacteria count and decreasing the harmful bacteria count. These findings indicated that MOP can regulate bone formation through the BMP/Smads signaling pathway, attenuating oxidative stress and regulating the gut microbiota of TD broilers, so as to achieve the effect of treating TD. This suggests that MOP might be a potential novel drug in the treatment of TD in chickens.