Human diet-derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization.

This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-ß, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.

Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation.

Background and aim: Diabetic Kidney Disease (DKD) is a common microvascular complication of diabetes mellitus. Multi-center, randomized controlled trials have shown that Qidan Dihuang Granule (QDDHG) reduces the levels of albuminuria of DKD. However, the specific mechanisms of QDDHG on DKD are not clarified. Thus, this study utilized network pharmacology, UHPLC-MS/MS (Ultra-High Performance Liquid Chromatography - Mass Spectrometry) and animal experiments to reveal the mechanisms of QDDHG on DKD. Experimental procedure: Screening and retrieving active ingredients and corresponding targets of QDDHG on DKD through the TCMSP, ETCM, Disgenet, GeneCards, Omim and DrugBank databases. The PPI were performed with BioGrid, STRING, OmniPath, InWeb-IM. AutoDock Vina molecular docking module to estimate the validation from the compounds and target proteins. Free energy to estimate the binding affinity for identified compounds and target proteins. The ingredients of QDDHG were analyzed utilizing UHPLC-MS/MS. In vivo experiment with db/db mice were used to verify the targets and pathway predicted by network pharmacology. Results and conclusion: The results demonstrated that QDDHG has 18 active compounds and 13 target proteins of QDDHG exerted a crucial role in treatment of DKD. QDDHG affect the multiple biological processes included cellular response to lipid, response to oxidative stress, and various pathways, such as AGE-RAGE, PI3K-Akt, MAPK, TNF, EGFR, STAT3. The results of UHPLC-MS/MS showed that six ingredients predicted by network pharmacology were also verified in experiment. In vivo experiment verified the effects of QDDHG on protecting the renal function mainly through inhibited the expression of EGFR, STAT3 and pERK in the db/db mice.

Multi-omics analysis reveals the molecular regulatory network underlying the prevention of Lactiplantibacillus plantarum against LPS-induced salpingitis in laying hens.

BACKGROUND: Salpingitis is one of the common diseases in laying hen production, which greatly decreases the economic outcome of laying hen farming. Lactiplantibacillus plantarum was effective in preventing local or systemic inflammation, however rare studies were reported on its prevention against salpingitis. This study aimed to investigate the preventive molecular regulatory network of microencapsulated Lactiplantibacillus plantarum (MLP) against salpingitis through multi-omics analysis, including microbiome, transcriptome and metabolome analyses. RESULTS: The results revealed that supplementation of MLP in diet significantly alleviated the inflammation and atrophy of uterus caused by lipopolysaccharide (LPS) in hens (P < 0.05). The concentrations of plasma IL-2 and IL-10 in hens of MLP-LPS group were higher than those in hens of LPS-stimulation group (CN-LPS group) (P < 0.05). The expression levels of TLR2, MYD88, NF-κB, COX2, and TNF-α were significantly decreased in the hens fed diet supplemented with MLP and suffered with LPS stimulation (MLP-LPS group) compared with those in the hens of CN-LPS group (P < 0.05). Differentially expressed genes (DEGs) induced by MLP were involved in inflammation, reproduction, and calcium ion transport. At the genus level, the MLP supplementation significantly increased the abundance of Phascolarctobacterium, whereas decreased the abundance of Candidatus_Saccharimonas in LPS challenged hens (P < 0.05). The metabolites altered by dietary supplementation with MLP were mainly involved in galactose, uronic acid, histidine, pyruvate and primary bile acid metabolism. Dietary supplementation with MLP inversely regulates LPS-induced differential metabolites such as LysoPA (24:0/0:0) (P < 0.05). CONCLUSIONS: In summary, dietary supplementation with microencapsulated Lactiplantibacillus plantarum prevented salpingitis by modulating the abundances of Candidatus_Saccharimonas, Phascolarctobacterium, Ruminococcus_torques_group and Eubacterium_hallii_group while downregulating the levels of plasma metabolites, p-tolyl sulfate, o-cresol and N-acetylhistamine and upregulating S-lactoylglutathione, simultaneously increasing the expressions of CPNE4, CNTN3 and ACAN genes in the uterus, and ultimately inhibiting oviducal inflammation.

[Separation, characterization, and antiviral activity of colloidal phase state of Maxing Shigan Decoction].

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.

Insomnia and circadian rhythm: a bibliometrics study and visualization analysis via CiteSpace.

Objective: The present study aimed to use CiteSpace to analyze the status of insomnia and circadian rhythm, identify the hot spots and trends, and provide a basis for future study. Method: The Web of Science database was searched for studies related to insomnia and circadian from its inception to 14 April 2023. CiteSpace was used to generate online maps of collaboration between countries and authors and revealed hot spots and frontiers in insomnia and circadian rhythm. Results: We searched 4,696 publications related to insomnia and circadian rhythm. Bruno Etain was the most prolific author with most publications, i.e., with 24 articles. The USA and the University of California were the leading country and the top institution in this field of study, with 1,672 and 269 articles, respectively. There was active cooperation between institutions, countries, and authors. Hot topics focused on circadian rhythm sleep disorders, circadian clock, light therapy, melatonin, and bipolar disorder. Conclusion: Based on the CiteSpace results, we recommend a more active collaboration between various countries, institutions, and authors to conduct clinical and basic research related to insomnia and circadian rhythm. Ongoing research focuses on the interaction of insomnia with circadian rhythms and the corresponding pathways of clock genes and by extension, the role of circadian rhythms in disorders such as bipolar disorder. Modulation of circadian rhythms may be a hot spot for future insomnia therapies (such as light therapy and melatonin).

[Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3/caspase-1/GSDMD pyroptosis pathway].

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1ß(IL-1ß) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.

Screening potential ligands of endothelin receptor A from Choerospondias axillaris and evaluation of their drug-like properties by affinity chromatographic methods.

Tibetan medicine is traditionally prescribed as crude extracts or mixtures owing to the theoretical basis with cross fertilization from other medical systems like Ayurveda and traditional Chinese medicine. This is challenged to elucidate the action mechanism and material foundation of Tibetan medicine due to lacking a method to confirm the bioactive compounds determining the therapy. This work created a new strategy for screening and evaluating the bioactive compounds against cardiovascular ailments from Choerospondias axillaris. It involved the immobilization of endothelin receptor A (ETAR) by a one-step covalent assay, the screening and identification of the bioactive compounds by ETAR column combined with tandem mass spectrometry, and the evaluation of their drug-like properties by calculating the efficiency indexes using the data collected by frontal analysis and adsorption energy distribution. The immobilized ETAR remained good stability in three weeks in terms of specificity and repeatability. Catechin, pinocembrin, and hyperoside were identified as potential ETAR ligands from Choerospondias axillaris with two types of binding sites on the immobilized receptor. Their association constants on the high and low affinity binding sites were (2.53 ± 0.11) × 105 and (9.94 ± 0.02) × 103 M-1 for catechin, (1.01 ± 0.12) × 106 and (7.40 ± 0.03) × 104 for hyperoside, and (2.05 ± 0.04) × 105 and (2.47 ± 0.09)× 104 M-1 for pinocembrin, respectively. Owing to the highest association constant, hyperoside presented a surface efficiency index of 7.95, and binding efficiency index of 20.7, and the ligand-lipophilicity efficiency of 1.38. These indicated that the three compounds were the main ingredients for the therapy of Choerospondias axillaris, and had potential to become lead compounds for anti-cardiovascular drugs based on drug-ETAR interaction. The immobilized receptor-based strategy is possible to become an alternative for screening and assessing bioactive compounds from Tibetan medicine.

Preliminary verification of the anti-hypoxia mechanism of Gentiana straminea maxim based on UPLC-triple TOF MS/MS and network pharmacology.

BACKGROUND: Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear. METHODS: Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim's ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim's ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim's ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds' anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock. RESULTS: Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski's rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets. CONCLUSIONS: The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.

Yin and yang regulation of stress granules by Caprin-1.

Stress granules (SGs) are cytoplasmic biomolecular condensates containing proteins and RNAs in response to stress. Ras-GTPase-activating protein binding protein 1 (G3BP1) is a core SG protein. Caprin-1 and ubiquitin specific peptidase 10 (USP10) interact with G3BP1, facilitating and suppressing SG formation, respectively. The crystal structures of the nuclear transport factor 2-like (NTF2L) domain of G3BP1 in complex with the G3BP1-interacting motif (GIM) of Caprin-1 and USP10 show that both GIMs bind to the same hydrophobic pocket of G3BP1. Moreover, both GIMs suppressed the liquid-liquid phase separation (LLPS) of G3BP1, suggesting that Caprin-1 likely facilitates SG formation via other mechanisms. Thus, we dissected various domains of Caprin-1 and investigated their role in LLPS in vitro and SG formation in cells. The C-terminal domain of Caprin-1 underwent spontaneous LLPS, whereas the N-terminal domain and GIM of Caprin-1 suppressed LLPS of G3BP1. The opposing effect of the N- and C-terminal domains of Caprin-1 on SG formation were demonstrated in cells with or without the endogenous Caprin-1. We propose that the N- and C-terminal domains of Caprin-1 regulate SG formation in a "yin and yang" fashion, mediating the dynamic and reversible assembly of SGs.

κ-Opioid Receptor Agonist U50448H Protects Against Acute Lung Injury in Rats with Cardiopulmonary Bypass via the CAP-NLRP3 Signaling Pathway.

Objective: Acute lung injury (ALI) is one of the common and severe complications of cardiopulmonary bypass (CPB), which is the primary cause of death in intensive care units. Nevertheless, there is a lack of effective treatment for ALI secondary to CPB. κ-Opioid receptor (KOR) agonists have been demonstrated to improve lung function after pulmonary hypertension. However, its protective role has been barely reported in CPB-induced acute respiratory distress syndrome (ARDS). Therefore, this research focused on the protective effect of a KOR agonist U50448H on ARDS and investigated its potential relationship with the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Method: Forty-five rats were randomly allocated into Sham, CPB, and U50448 groups (n = 15 rats/group). After a CPB model was successfully established in rats, CPB rats were treated with the KOR agonist U50448H. The values of extravascular lung water (EVLW), alveolar-arterial oxygen tension difference (AaDO2), and respiratory index (RI) were examined, and the lung wet/dry (W/D) weight ratio was also calculated. Western blot (WB) was utilized to measure the expression of MMP-9, GSDMD-C, GSDMD-N, NLRP3, ASC, pro-Caspase-1, pro-IL-1ß, and α7-nAChR. The immunofluorescence assay was performed for examining the expression of ROS, F480, iNOS, CD206, and α7-nAChR. Cell apoptosis was detected by the TUNEL assay. ELISA was used to test the level of LPS in serum and the level of MDA, GSH, SOD, TNF-α, IL-4, IL-6, IL-18, and IL-1ß in lung tissues. Results: It was observed that the administration of U50448H significantly reduced EVLW values and LPS levels in the lung of rats. Meanwhile, U50448H increased AaDO2 values while decreasing RI values. Moreover, the administration of U50448H alleviated the pathological damage caused by ALI secondary to CPB. U50448H repressed ROS release and oxidative stress responses, as well as lowered LPS levels in plasma and MMP-9 expression in the lung of CPB rats. Furthermore, U50448H facilitated the shift of macrophage phenotype to M2. In addition, U50448H decreased the activity of the CAP-NLRP3 inflammasome and suppressed pyroptosis in pulmonary cells. Conclusion: The KOR agonist U50448H improved lung function and relieved lung injury in CPB rats, accompanied by diminished ROS and MMP-9 levels in lung tissues, promoted macrophage polarization from M1 to M2, and reduced NLRP3 inflammasome activities. These results indicated U50448H as a promising drug for the treatment of ALI secondary to CPB.

Effects of traditional Chinese medicine-based exercises on cognitive function in older people with mild cognitive impairment: A systematic review and meta-analysis.

This study evaluated the effects of traditional Chinese medicine based exercise (TCE) on cognitive outcomes for patients with mild cognitive impairment (MCI), and tried to identify the most effective TCE modality. A systematic review and meta-analysis of randomized controlled trials were conducted. Ten studies met the inclusion criteria. TCE interventions were classified into three types: (a) Tai Chi, (b) Baduanjin, and (c) Qigong. The pooled analysis showed that, overall, TCE had beneficial effects on global cognition and memory. Subgroup analysis further demonstrated that Baduanjin had a larger effect size on global cognition than the other TCE modalities. By contrast, Tai Chi had a larger effect size on memory than the other modalities. This study implied that TCE is a promising exercise option for improving cognition in MCI. However, further studies with a more rigorous study design are warranted to support or falsify the findings of the present review.

Association Between Plasma Vitamin D2 and Type 2 Diabetes Mellitus.

Objective: To investigate the relationship between plasma vitamin D2(VD2) and type 2 diabetes(T2DM). Method: Data from electronic medical records of 797 inpatients treated at Sun Yat Sen Memorial Hospital, Sun Yat-sen University between June 24, 2019 and December 24, 2020 were collected, and a total of 596 patients were enrolled after screening based on inclusion and exclusion criteria. Patients were divided into diabetic and non-diabetic groups according to whether they had T2DM. The Wilcoxon rank sum test was finally selected for the analysis of differences between groups according to the distribution of patients' plasma VD2, and logistic regression models were used to find the corresponding influencing factors. Result: Of the 596 hospitalized patients, 138 (23.15%) were diagnosed with T2DM. The Wilcoxon test showed no statistically significant difference in plasma VD2 concentrations between the T2DM and non-T2DM groups (p=0.833). After adjustment for confounders by multivariate logistic regression, there was still no significant difference in plasma VD2 concentrations between the two groups (P=0.316, OR: 1.15 (0.88,1.49)). The uncorrelated relationship between VD2 and T2DM was not found to change after incorporating 12 indicators, including demographic characteristics, laboratory indicators and complications, into the logistic regression model by 3 steps, even the OR (1.08 (0.92,1.26)) did not change in the 3 models. Similarly, the adjusted ORs agreed that there was no statistical association between VD2 and T2DM. Conclusion: VD2 levels are similar in patients with T2DM compared to those without T2DM. Clinical caution should be exercised in giving VD2 supplementation to patients with T2DM unless other diseases requiring VD2 supplementation (e.g., rickets, osteoporosis) are present.

Effective Parts of Gentiana straminea Maxim Attenuates Hypoxia-Induced Oxidative Stress and Apoptosis.

Hypoxia occurs in physiological situations and several pathological situations, inducing oxidative stress. G straminea Maxim (G.s Maxim) is a traditional Tibetan medicine that exerts several biological effects. This study focused on the protective effects of G.s Maxim in hypoxia-induced oxidative stress and apoptosis. We found that G.s Maxim significantly increased survival and reduced oxidative stress in hypoxic mice. Various extraction parts of G.s Maxim showed antioxidant activity and significantly improved survival in hypoxia-injured PC12 cells. G.s Maxim reduced hypoxia-induced cell apoptosis and leakage of lactate dehydrogenase. Hypoxic cells had increased malondialdehyde levels but reduced superoxide dismutase activity and G.s Maxim reversed these effects. Moreover, G.s Maxim suppressed hypoxia-induced apoptosis by inducing protein expression of B cell leukemia/lymphoma-2 and reducing the expression of hypoxia-inducible factor-1α, Bcl-2-associated X, and nuclear factor-k-gene binding. These findings suggest that G.s Maxim attenuates hypoxia-induced injury associated with oxidative stress and apoptosis.

Effects of synbiotic on growth, digestibility, immune and antioxidant performance in broilers.

The overuse of in-feed antibiotics has been associated with serious issues, including the developing of antibiotic-resistant pathogens and causing drug residues in poultry products. To date, many countries have restricted the use of growth-promoting antibiotics in food animals, resulting in the increased need for effective alternatives to in-feed antibiotic. Synbiotics, which are composed of probiotics and prebiotics, have been shown to act synergistically when applied simultaneously. Thus, this study investigated the effects of a synbiotic, composed of microencapsulated Lactobacillus plantarum (MLP) and fructooligosaccharide (FOS), on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus in broilers. A total of 168 newly hatched male broilers were randomly allotted to three dietary groups (n = 7): (1) a corn-soybean meal basal diet (CON); (2) basal diet + synbiotic (SYN); and (3) basal diet + aureomycin (ANT). Compared with the CON, chickens had greater average daily gain and digestibility of calcium and phosphorus in the SYN group (P < 0.05). In the SYN and ANT group, serum IgA, IgG, and IL-10 levels were higher, while the serum TNF-α, IL-2, and IL-6 levels were reduced (P < 0.05) compared to CON. Compared with CON, the level of serum malondialdehyde was lower (P < 0.05) and SOD level was higher (P < 0.05) in either SYN or ANT group. No significant differences in populations of Escherichia coli were seen in chickens among the three groups, whereas, the populations of Lactobacillus were higher (P < 0.05) in chickens in the SYN group compared with those in CON and ANT groups. Taken together, the addition of SYN, consisting of MLP and FOS, had benefits on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus, indicating its potential to serve as a substitute for antibiotics in broiler feeding.

Phosphorus removal from municipal wastewater through a novel Trichosporon asahii BZ: Performance and mechanism.

A yeast BZ was screened from a laboratory-scale anaerobic/aerobic reactor and designated as Trichosporon asahii through 26S rDNA gene sequence analysis. The screened BZ abated over 70% of phosphorus in municipal sewage with 2-10 mg/L phosphorus in the appropriate conditions. The yeast BZ had strong adaptability to pH and the dissolved oxygen, but the cultivation temperature, carbon source, the ratio of C/P and the ratio of N/P had a critical influence on the phosphorus abatement performance of yeast BZ. The analysis of phosphorus concentration in the wastewater, cells, and extracellular polymeric substances (EPS) suggested that about 55%-66% of the removed phosphorus was in the yeast cells and 34%-45% in the EPS. The proposed probable metabolic mechanism of phosphorus in yeast BZ showed that EPS acted as a dynamic phosphorous transfer station, and most of phosphorus was transferred into yeast cells through EPS transfer station. These findings have crucial implications for the development of a promising stable and easy-operation biological phosphorus abatement process for municipal wastewater treatment.

Old dog, new tricks: Polydatin as a multitarget agent for current diseases.

Polydatin (PD) is a natural single-crystal product that is primarily extracted from the traditional plant Polygonum cuspidatum Sieb. et Zucc. Early research showed that PD exhibited a variety of biological activities. PD has attracted increasing research interest since 2014, but no review comprehensively summarized the new findings. A great gap between its biological activities and drug development remains. It is necessary to summarize new findings on the pharmacological effects of PD on current diseases. We propose that PD will most likely be used in cardiac and cerebral ischaemia/reperfusion-related diseases and atherosclerosis in the future. The present work classified these new findings according to diseases and summarized the main effects of PD via specific mechanisms of action. In summary, we found that PD played a therapeutic role in a variety of diseases, primarily via five mechanisms: antioxidative effects, antiinflammatory effects, regulation of autophagy and apoptosis, maintenance of mitochondrial function, and lipid regulation.

Comparative Evidence for Intrahepatic Cholestasis of Pregnancy Treatment With Traditional Chinese Medicine Therapy: A Network Meta-Analysis.

Background: Intrahepatic cholestasis of pregnancy (ICP) seriously threatens the health of pregnant women and newborns. A various number of Chinese prescriptions and patent medicines combined with ursodeoxycholic acid (UDCA) are used for treating ICP in China. However, there are still many doubts in choosing the suitable therapeutic drugs for the treatment of ICP in clinical practice. Methods: Several electronic databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), Wanfang, and VIP, were comprehensively searched from the database inception to February 22, 2021. Randomized controlled trials (RCTs) reporting the use of UDCA only, Chinese prescriptions plus UDCA, and patent medicine plus UDCA for the treatment of ICP were collected according to their inclusion and exclusion criteria. Cochrane Reviewers' Handbook version 5.2 was applied for the risk assessment of the included trials. STATA 16.0 software was used for network meta-analysis (NMA). The pruritus score and the serum levels of total bile acid (TBA), alanine aminotransferase (ALT), and aspartate transaminase (AST) in ICP patients served as the primary outcomes. Moreover, this study had been registered in PROSPERO (https://www.crd.york.ac.uk/PROSPERO/#joinuppage), and the registration number is CRD42020188831. Results: Thirty-eight RCTs comprising 3,841 patients meeting the inclusion criteria were included in the network meta-analysis. The NMA results showed that compared with UDCA used alone, Yinchenhao decoction (seven different Chinese prescriptions or patent medicines) plus UDCA dramatically alleviated the primary outcomes of ICP, including the pruritus score, as well as the serum levels of TBA, ALT, and AST. The NMA results showed that the optimal drug ratio for the treatment of ICP was different from the dosage ratio of traditional Yinchenhao decoction. Significantly, the intervention plan f (IP-f) group [the similar prescription of Yinchenhao decoction 2 (Artemisia capillaris Thunb >15 g, Gardenia >9 g, and Rhubarb <5 g) + UDCA] was the best therapeutics among the eight therapies. Conclusion: Overall, the combined use of Chinese prescriptions or patent medicine with UDCA was generally better than UDCA used alone. The dose of IP-f might be a beneficial therapeutic method for the clinical medication of ICP. Clinical Trail Registration: https://www.crd.york.ac.uk/, identifier CRD42020188831.

Qi-Regulating and Blood Circulation-Promoting Therapy Improves Health Status of Stable Angina Pectoris Patients with Depressive Symptoms.

Depressive symptoms have been found to be highly prevalent among patients with coronary heart disease (CHD) and seriously affect the patients' quality of life. However, most psychotropic drugs have warnings about potential side effects. Accordingly, safer effective alternatives are urgently demanded. Angina pectoris of CHD is considered as "chest stuffiness and heartache syndrome" in traditional Chinese medicine, with the major syndrome type named Qi stagnation and blood stasis. Qi-regulating and blood circulation-promoting therapy has increasingly shown unique advantages in CHD patients. This study investigated the efficacy of Xuefu Zhuyu decoction, a representative prescription of Qi-regulating and blood circulation-promoting therapy, on angina pectoris patients with depressive symptoms. Depressive symptoms were stratified at baseline in 30 patients with stable angina pectoris who participated in both baseline and 12-week follow-up studies. After performing a stratified analysis, the angina pectoris-specific health status and traditional Chinese medicine "chest stuffiness and heartache syndrome" were evaluated by self-reports using the associated questionnaire scales, respectively. We measured serum concentrations of serotonin, brain-derived neurotrophic factor, and ATP, which are associated with the development of depression. We found that the Xuefu Zhuyu granule significantly improved the angina pectoris-specific health status in patients after 12 weeks of treatment; specifically, it had a better curative effect on patients with depressive symptoms. Xuefu Zhuyu granule also significantly improved the chest stuffiness and heartache syndrome in patients with depressive symptoms (efficacy index is 61.24%, P < 0.05 versus baseline). Interestingly, Xuefu Zhuyu granule has been found to be more susceptible to improving ATP levels in patients with depressive symptoms, indicating that the improvement in serum ATP levels might account for the better efficacy of Xuefu Zhuyu granule in patients with depressive symptoms. Our data provide prospective evidence that Xuefu Zhuyu granule improves angina pectoris-specific health status through regulating Qi and promoting blood circulation. This trial is registered with ChiCTR-IOR-15006989.

Coenzyme Q10 ameliorates BPA-induced apoptosis by regulating autophagy-related lysosomal pathways.

Bisphenol A (BPA) is a widely distributed environmental endocrine disruptor. The accumulation of BPA has been proved that produce various toxic effects both on human and animals. However, the strategies to reduce the damage of BPA on the body and related mechanisms remain to be studied. Coenzyme Q10 (CoQ10), as a powerful antioxidant, is ubiquitous in many eukaryotic cells, which can improve the integrity of lysosomal membrane, lysosomal degradation function and promote autophagy. Here, we examined the ability of CoQ10 to alleviate oxidative stress and apoptosis in BPA-induced damages in C2C12 cells, and how to alleviate it. Our results showed that BPA treatment significantly reduced cell viability, increased the number of cell apoptosis and ROS production, decreased mitochondrial membrane potential, and inhibited the gene expression of mitochondria biogenesis. Moreover, we demonstrated that exposure to BPA increased expression levels of autophagy protein (LC3-II, p62), inhibited autophagy flux, and disrupted the acidic pH environment of lysosomes. Importantly, CoQ10 supplementation effectively restored these abnormalities caused by BPA. CoQ10 significantly decreased the apoptotic incidence and ROS levels, improved mitochondrial membrane potential. Moreover, CoQ10 improved lysosome function and enhanced autophagy flux. Taken together, our results indicate that CoQ10 supplementation is a feasible and effective way to promote the level of autophagy by improving lysosomal function, thereby reducing the apoptosis caused by BPA accumulation. This study aims to provide evidence for the role of CoQ10 in repairing BPA-induced cell damage in clinical practice.

The relationship between host circadian rhythms and intestinal microbiota: A new cue to improve health by tea polyphenols.

Under the control of the host circadian rhythms, intestinal microbiota undergoes dietary-dependent diurnal fluctuations in composition and function. In addition, microbiome plays a critical role in maintaining the host circadian rhythms and metabolic homeostasis. The interactions between host circadian rhythms and intestinal microbiota suggest that intervention with prebiotics or probiotic is a possible way to alleviate circadian rhythm misalignment and related metabolic diseases. This review discusses the circadian rhythm oscillations of gut flora, relationship between host circadian rhythms and microbiome and related effects on metabolism. The influence on circadian rhythms by the interactions between tea polyphenols (TP) and intestinal microbiota is highlighted.