Effects of Tetrabasic Zinc Chloride on the Diarrhea Rate, Intestinal Morphology, Immune Indices and Microflora of Weaned Piglets.

This study was aimed to investigate the effects of different dietary zinc sources on the diarrhea rate, intestinal morphology, immune indexes and intestinal microbial composition of weaned piglets. A total of 240 weaned piglets (Duroc × Landrace × Yorkshire), at the age of 21 days, were randomly assigned to five dietary treatments for a four-week feeding trial to determine the effects of different amounts of tetrabasic zinc chloride (TBZC) supplementation on intestinal morphology, intestinal immune indices and intestinal microflora in weaned piglets, compared with the pharmacological dose of ZnO. The dietary treatments included a negative control (CON), (T1) ZnO (ZnO, 1500 mg/kg), (T2) tetrabasic zinc chloride (TBZC, 800 mg/kg), (T3) tetrabasic zinc chloride (TBZC, 1000 mg/kg), and (T4) tetrabasic zinc chloride (TBZC, 1200 mg/kg). Each treatment comprised six replicate pens, with eight pigs (four barrows and four gilts) per pen. Dietary TBZC of 1200 mg/kg improved the duodenum villus height, jejunum villus height and crypt depth of ileum, and increased the ratio of villus height to crypt depth of ileum (p < 0.05). The dietary supplementation of TBZC at a dosage of 1200 mg/kg has the potential to increase the levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) in the duodenal mucosa. Furthermore, it shows a significant increase in the levels of immunoglobulin A (IgA) in the ileum. Compared with CON, TBZC significantly (p < 0.05) decreased pH values of stomach contents. It also increased the number of Firmicutes in intestinal contents. Compared with CON, the abundance of Firmicutes in jejunum contents of other treatments was significantly improved (p < 0.05), while the abundance of Proteobacteria in ileum contents of high-zinc treatments (T2 and T5) was decreased (p < 0.05). In conclusion, dietary TBZC of 1200 mg/kg improved the digestibility of crude protein in weaned piglets, altered the intestinal morphology of piglets, changed the intestinal microflora of piglets, reduced the diarrhea rate, and significantly improved the development of the small intestine of weaned piglets, and its regulation mechanism on intestinal tract needs further study. In summary, TBZC is likely to be an effective substitute source for the pharmacological dose of ZnO to control diarrhea in weaned piglets.

Carbon-negative and high-rate nutrient recovery from municipal wastewater using mixotrophic Scenedesmus acuminatus.

The efficiency of mixotrophic microalgae in enhancing the recovery of waste nutrients has been well established; however, the recovery rate is crucial in meeting the needs of field applications. This study evaluated the impact of media characteristics on nutrient recovery under mixotrophic conditions. The mixotrophic N recovery rate with S. acuminatus in modified BG-11 reached 2.59 mg L-1h-1. A mixotrophic growth optimization strategy was applied to achieve a high-rate nutrient recovery from municipal wastewater treatment plant effluents. The contribution of waste chemical oxygen demand (COD) to nutrient recovery was assessed using secondary effluent (SE) under heterotrophy. The results highlighted a significant increase in total nitrogen (TN) and total phosphorus (TP) recovery rates when glucose was supplied, indicating the additional carbon requirements for efficient nutrient recovery. The TN and TP recovery rates under mixotrophic conditions with the addition of trace metals and high cell density were enhanced by 91.94% and 92.53%, respectively, resulting in recovery rates of 3.43 mg L-1h-1 and 0.30 mg L-1h-1. The same conditions were used for nutrient recovery from primary effluent (PE), and the results were more satisfactory as the TN and TP recovery rates reached 4.79 and 0.55 mg L-1h-1, respectively. Additionally, the study estimated the carbon footprints (C-footprints) and areal footprints of mixotrophy-based nitrogen recovery. The findings revealed carbon footprints and areal footprints of -15.93 ± 4.57 tCO2e t-1 N recovery and 0.53 ± 0.19 m3 m-2d-1 wastewater, respectively. This high-rate nutrient recovery, achieved under a carbon-negative (C-negative) budget through mixotrophy, presents a novel strategy for efficiently recovering resources from municipal wastewater, thus facilitating resource recycling and ensuring environmental sustainability.

Light-Driven Biomimetic Nanomotors for Enhanced Photothermal Therapy.

Nanotechnology-based strategy has recently drawn extensive attention for the therapy of malignant tumors due to its distinct strengths in cancer diagnosis and treatment. However, the limited intratumoral permeability of nanoparticles is a major hurdle to achieving the desired effect of cancer treatment. Due to their superior cargo towing and reliable penetrating property, micro-/nanomotors (MNMs) are considered as one of the most potential candidates for the coming generation of drug delivery platforms. Here, near-infrared (NIR)-actuated biomimetic nanomotors (4T1-JPGSs-IND) are fabricated successfully and we demonstrate that 4T1-JPGSs-IND selectively accumulate in homologous tumor regions due to the effective homing ability. Upon laser irradiation, hyperthermia generated by 4T1-JPGSs-IND leads to self-thermophoretic motion and photothermal therapy (PTT) to ablate tumors with a deep depth, thereby improving the photothermal therapeutic effect for cancer management. The developed nanomotor system with multifunctionalities exhibits promising potential in biomedical applications to fight against various diseases.

Long-term nitrogen fertilization and sweetpotato cultivation in the wheat-sweetpotato rotation system decrease alkaline phosphomonoesterase activity by regulating soil phoD-harboring bacteria communities.

The alkaline phosphomonoesterase (ALP)-harboring community (phoD-harboring community) plays a crucial role in the conversion of organic phosphorus (P) into available P (AP). However, the response mechanisms of phoD-harboring communities to fertilization strategies, crop types, and their interactions within the wheat-sweetpotato rotation are poorly understood. A nine-year field experiment of different fertilization strategies was established under the wheat-sweetpotato rotation. After harvesting the crop, we collected soil samples without fertilization (CK), inorganic NK fertilization (NK), inorganic NPK fertilization (NPK), and a combined application of inorganic NPK and organic fertilizer (NPKM). We employed high-throughput sequencing and enzymology techniques to analyze the composition and functional activity of phoD-harboring bacterial communities as well as their correlation with soil physicochemical properties. The results showed that long-term nitrogen (N) fertilization, especially inorganic N, significantly reduced soil pH and ALP activity while increasing AP compared with CK. The AP content in sweetpotato season was significantly higher than that in wheat season. Inorganic N fertilization dramatically reshaped the communities of phoD-harboring bacteria and decreased diversity. The phoD-harboring bacterial communities in sweetpotato season were significantly different from those in wheat season. The N fertilization significantly reduced the relative abundance of Acuticoccus, Methylibium, Rhizobacter, and Roseivivax, which was positively correlated with ALP activity. These groups in sweetpotato season decreased significantly compared with wheat season. A structural equation model indicates that pH and AP play a significant role in regulating the phoD-harboring bacteria communities, ALP activity, and their interactions. We demonstrate that fertilization strategies and crop types have a substantial impact on the phoD-harboring bacteria communities and functions, which are closely linked to soil pH and AP levels. Our study highlights the detrimental effects of soil acidification resulting from inorganic N fertilization on P-cycling bacterial communities and functions. However, the combination of inorganic and organic fertilizer can mitigate these adverse effects.

IL5RA as an immunogenic cell death-related predictor in progression and therapeutic response of multiple myeloma.

Previous studies have shown the potential of immunogenic cell death-related modalities in myeloma. The significance of IL5RA in myeloma and immunogenic cell death remains unknown. We analyzed IL5RA expression, the gene expression profile, and secretory protein genes related to IL5RA level using GEO data. Immunogenic cell death subgroup classification was performed using the ConsensusClusterPlus and pheatmap R package. Enrichment analyses were based on GO/KEGG analysis. After IL5RA-shRNA transfection in myeloma cells, cell proliferation, apoptosis, and drug sensitivity were detected. P < 0.05 was considered statistically significant. IL5RA was upregulated in myeloma and progressed smoldering myeloma. We observed enrichment in pathways such as the PI3K-Akt signaling pathway, and Natural killer cell mediated cytotoxicity in the high-IL5RA group. IL5RA was also closely associated with secretory protein genes such as CST6. We observed the enrichment of cellular apoptosis and hippo signaling pathway on differential genes in the immunogenic cell death cluster. Furthermore, IL5RA was associated with immune infiltration, immunogenic cell death-related genes, immune-checkpoint-related genes, and m6A in myeloma. In vitro and in vivo experiments showed the involvement of IL5RA in apoptosis, proliferation, and drug resistance of myeloma cells. IL5RA shows the potential to be an immunogenic cell death-related predictor for myeloma.

Potential molecular mechanisms of Erlongjiaonang action in idiopathic sudden hearing loss: A network pharmacology and molecular docking analyses.

Background: Idiopathic sudden hearing loss (ISHL) is characterized by sudden unexplainable and unilateral hearing loss as a clinically emergent symptom. The use of the herb Erlongjiaonang (ELJN) in traditional Chinese medicine is known to effectively control and cure ISHL. This study explored the underlying molecular mechanisms using network pharmacology and molecular docking analyses. Method: The Traditional Chinese Medicine System Pharmacological database and the Swiss Target Prediction database were searched for the identification of ELJN constituents and potential gene targets, respectively, while ISHL-related gene abnormality was assessed using the Online Mendelian Inheritance in Man and Gene Card databases. The interaction of ELJN gene targets with ISHL genes was obtained after these databases were cross-screened, and a drug component-intersecting target network was constructed, and the gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction networks were analyzed. Cytoscape software tools were used to map the active components-crossover target-signaling pathway network and screened targets were then validated by establishing molecular docking with the corresponding components. Result: Erlongjiaonang contains 85 components and 250 corresponding gene targets, while ISHL has 714 disease-related targets, resulting in 66 cross-targets. The bioinformatical analyses revealed these 66 cross-targets, including isorhamnetin and formononetin on NOS3 expression, baicalein on AKT1 activity, and kaempferol and quercetin on NOS3 and AKT1 activity, as potential ELJN-induced anti-ISHL targets. Conclusion: This study uncovered potential ELJN gene targets and molecular signaling pathways in the control of ISHL, providing a molecular basis for further investigation of the anti-ISHL activity of ELJN.

Alleviating Effect of Lacticaseibacillus rhamnosus 1.0320 Combined with Dihydromyricetin on Acute Alcohol Exposure-Induced Hepatic Impairment: Based on Short-Chain Fatty Acids and Adenosine 5'-Monophosphate-Activated Protein Kinase-Mediated Lipid Metabolism Signaling Pathway.

Excessive drinking has been listed by the World Health Organization as the fifth major risk factor; especially the liver, as the core organ of alcohol metabolism, is prone to organic lesions. Probiotics have received attention due to their bioactivity for liver protection. The beneficial effects of probiotics on hosts are related to their physiological functions. Therefore, based on the concept of second-generation synbiotes, this study explored the protective effects of four dietary polyphenols on the stress tolerance, hydrophobicity, adhesion, and digestive characteristics of L. rhamnosus 1.0320. L. rhamnosus 1.0320 had the best synergistic effect with dihydromyricetin (DMY). Therefore, this combination was selected as a synbiotic supplement to explore the protective effect on acute alcohol exposure-induced hepatic impairment. The results showed that L. rhamnosus 1.0320 combined with DMY restored the intestinal barrier by upregulating short-chain fatty acid levels and activated the adenosine 5'-monophosphate-activated protein kinase-mediated lipid metabolism pathway to inhibit oxidative stress, inflammation, and lipid accumulation in the liver. Furthermore, 109 CFU/mouse/d L. rhamnosus 1.0320 and 50 mg/kg/d DMY by gavage were identified as the optimal doses for protection against acute alcohol expose-induced hepatic impairment. This study provides new insights into alleviating acute alcoholic hepatic impairment by targeting intestinal metabolites through the gut-liver axis.

Cedrol, a Ginger-derived sesquiterpineol, suppresses estrogen-deficient osteoporosis by intervening NFATc1 and reactive oxygen species.

Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Ginger, a food spice and traditional medicine with ancient history, exhibits the potential to alleviate osteoporosis in preclinical experiments, whereas its complex composition leads to ambiguous pharmacological mechanisms. The purpose of this study was to investigate the effect and mechanism of Ced in estrogen-deficient osteoporosis, a sesquiterpene alcohol recently discovered from Ginger with multiple pharmacological properties. RANKL was stimulated BMM (bone marrow macrophages) differentiation into osteoclasts in vitro. And the osteoclast activity and number were assessed by TRAcP and SEM. We found that Ced mitigated RANKL-induced osteoclastogenesis by descending the ROS content and obstructing NFATc1, NF-κB, and MAPK signaling. Also, Ced-mediated anti-osteolytic property was found in ovariectomized mice by Micro-CT scanning and histological staining. Summarily, our works demonstrated the anti-osteoporotic potential of Cedrol in Ginger for the first time, which also offered more pharmacological evidence for Ginger as food or medicine used for bone metabolic disease.

Four Different Structural Dietary Polyphenols, Especially Dihydromyricetin, Possess Superior Protective Effect on Ethanol-Induced ICE-6 and AML-12 Cytotoxicity: The Role of CYP2E1 and Keap1-Nrf2 Pathways.

Polyphenols have received attention as dietary supplements for the relief of alcoholic liver disease (ALD) due to various bioactivities. Ethanol-induced rat small intestinal epithelial cell 6 (IEC-6) and alpha mouse liver 12 (AML-12) cell models were pretreated with four dietary polyphenols with different structures to explore their effects on cytotoxicity and potential protective mechanisms. The results showed that polyphenols had potential functions to inhibit ethanol-induced AML-12 and IEC-6 cell damage and oxidative stress, and restore ethanol-induced IEC-6 permeability and tight junction gene expression. Especially, dihydromyricetin (DMY) had the best protective effect on ethanol-induced cytotoxicity, followed by apigenin (API). Western blot results showed that DMY and API had the best ability to inhibit CYP2E1 and Keap1, and promote nuclear translocation of Nrf2, which might be the potential mechanism by which DMY and API attenuate ethanol-induced cytotoxicity. Moreover, the molecular docking results predicted that DMY and API could bind more tightly to the amino acid residues of CYP2E1 and Keap1, which might be one of the inhibitory modes of dietary polyphenols on CYP2E1 and Keap1. This study provided a rationale for the subsequent protective effect of dietary polyphenols on alcohol-induced liver injury in animal models and provided new clues on bioactive components for ALD-protection based on the gut-liver axis.

Arthritic Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy.

Increasing O2 demand and excessive ROS production are the main features of arthritic microenvironment in rheumatoid arthritis (RA) joints and further play pivotal roles in inflammation exacerbation. In this work, a system of in situ regulation of arthritic microenvironment based on nanomotor strategy is proposed for active RA therapy. The synthesized MnO2 -motors enable catalytic regulation of RA microenvironment by consuming the overproduced H2 O2 and generating O2 synergistically. The generated O2 under H2 O2 -rich conditions functions as inflammation detector, propellant for enhanced diffusion, as well as ameliorator for the hypoxic synovial microenvironment. Owing to O2 generation and inflammation scavenging, the MnO2 -motors block the re-polarization of pro-inflammatory macrophages, which results in significantly decreased secretion of multiple pro-inflammatory cytokines both in vitro and in vivo. In addition, intra-articular administration of MnO2 -motors to collagen-induced arthritis rats (CIA rats) effectively alleviates hypoxia, synovial inflammation, bone erosion, and cartilage degradation in joints. Therefore, the proposed arthritic regulation strategy shows great potential to seamlessly integrate basic research of RA with clinical translation.

Preparation of shell-core fiber-encapsulated Lactobacillus rhamnosus 1.0320 using coaxial electrospinning.

In this study, shell-core fibers were successfully prepared by using Eudragit S100 (ES100) and poly(vinyl alcohol) (PVA)/pectin (PEC) through coaxial electrospinning technology. The electrospun fiber was characterized by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Thermo-gravimetric analysis (TGA) showed that the coaxial electrospun fiber encapsulated with Lactobacillus rhamnosus 1.0320 (L. rhamnosus) had higher thermal stability than the electrospun fiber prepared by uniaxial electrospinning. L. rhamnosus encapsulated by coaxial electrospun fiber maintained 90.07% and 91.96% survivability in simulated gastric and intestinal fluids. After continuous simulated gastrointestinal fluid treatment, the survival rate of L. rhamnosus encapsulated by coaxial electrospun fiber was 81.40%. The results indicate that shell-core fiber-encapsulated probiotics can improve the tolerance of probiotics to the harsh environment of gastrointestinal tract. The fiber prepared in this study can be applied to the preparation of functional fermented food such as probiotic yogurt fermentation in the future.

Optimized Cationic Lipid-assisted Nanoparticle for Delivering CpG Oligodeoxynucleotides to Treat Hepatitis B Virus Infection.

PURPOSE: Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication. However, efficient delivery of CpG ODNs into pDCs and cDCs remains a challenge. In this study, we constructed a series of cationic lipid-assisted nanoparticles (CLANs) using different cationic lipids to screen an optimal nanoparticle for delivering CpG ODNs into pDCs and cDCs. METHODS: We constructed different CLANCpG using six cationic lipids and analyzed the cellular uptake of different CLANCpG by pDCs and cDCs in vitro and in vivo, and further analyzed the efficiency of different CLANCpG for activating pDCs and cDCs in both wild type mice and HBV-carrier mice. RESULTS: We found that CLAN fabricated with 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP) showed the highest efficiency for delivering CpG ODNs into pDCs and cDCs, resulting in strong therapeutic immunity in HBV-carrier mice. By using CLANCpG as an immune adjuvant in combination with the injection of recombinant hepatitis B surface antigen (rHBsAg), HBV was successfully eradicated and the chronic liver inflammation in HBV-carrier mice was reduced. CONCLUSION: We screened an optimized CLAN fabricated with DOTAP for efficient delivery of CpG ODNs to pDCs and cDCs, which can act as a therapeutic vaccine adjuvant for treating HBV infection.

Intestinal microbiomics and liver metabolomics insights into the preventive effects of chromium (III)-enriched yeast on hyperlipidemia and hyperglycemia induced by high-fat and high-fructose diet.

In recent years, organic chromium (III) supplements have received increasing attentions for their low toxicity, high bioavailability and wide range of health-promoting benefits. This study aimed to investigate the preventive effects of chromium (III)-enriched yeast (YCr) on high-fat and high-fructose diet (HFHFD)-induced hyperlipidemia and hyperglycemia in mice, and further clarify its mechanism of action from the perspective of intestinal microbiomics and liver metabolomics. The results indicated that oral administration of YCr remarkably inhibited the aberrant elevations of body weight, blood glucose and lipid levels, hepatic cholesterol (TC) and triglyceride (TG) levels caused by HFHFD. Liver histological examination showed that oral YCr intervention inhibited HFHFD induced liver lipid accumulation. Besides, 16S rDNA amplicon sequencing showed that YCr intervention was beneficial to ameliorating intestinal microbiota dysbiosis by altering the proportion of some intestinal microbial phylotypes. Correlation-based network analysis indicated that the key intestinal microbial phylotypes intervened by YCr were closely related to some biochemical parameters associated with glucose and lipid metabolism. Liver metabolomics analysis revealed that dietary YCr intervention significantly regulated the levels of some biomarkers involved in purine metabolism, glycerophospholipid metabolism, citrate cycle, pyrimidine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and so on. Moreover, dietary YCr intervention regulated the mRNA levels of key genes associated with glucose, cholesterol, fatty acids and bile acids metabolism in liver. These findings suggest that dietary YCr intervention has beneficial effects on glucose and lipid metabolism by regulating intestinal microbiota and liver metabolic pathway, and thus can be served as a functional component to prevent hyperlipidemia and hyperglycemia.

Organic chromium derived from the chelation of Ganoderma lucidum polysaccharide and chromium (III) alleviates metabolic syndromes and intestinal microbiota dysbiosis induced by high-fat and high-fructose diet.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Lactobacillus plantarum Combined with Galactooligosaccharides Supplement: A Neuroprotective Regimen Against Neurodegeneration and Memory Impairment by Regulating Short-Chain Fatty Acids and the c-Jun N-Terminal Kinase Signaling Pathway in Mice.

Probiotics and prebiotics have received attention in alleviating neurodegenerative diseases. Lactobacillus plantarum (L. plantarum) 69-2 was combined with galactooligosaccharides (GOS) and supplemented in a d-galactose (d-gal)-induced neurodegeneration and memory impairment mice model to explore its effects on the brain and the regulation of short-chain fatty acids. The results showed that the L. plantarum-GOS supplementation inhibited d-gal-induced oxidative stress and increased the brain's nuclear factor erythroid 2-related factor 2 (Nrf2) levels. Butyrate, a metabolite of the gut microbiota regulated by L. plantarum combined with GOS, inhibits p-JNK expression, downregulates pro-apoptotic proteins expression and the activation of inflammatory mediators, and upregulates synaptic protein expression. This might be a potential mechanism for L. plantarum 69-2 combined with GOS supplementation to alleviate d-gal-induced neurodegeneration and memory impairment. This study sheds new light on the development of aging-related neuroprotective dietary supplements based on the gut-brain axis.

Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1ß/NLRP3 inflammasome positive cycle.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1ß/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown. PURPOSE: This study aims to validate the role of Ory in IVDD and explore the potential mechanism. STUDY DESIGN: Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory. METHOD: The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1ß-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels. RESULTS: Ory treatment inhibited IL-1ß-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1ß/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development. CONCLUSION: Our results support the potential application of Ory as a therapeutic compound for IVDD.

Ganoderic acid A from Ganoderma lucidum protects against alcoholic liver injury through ameliorating the lipid metabolism and modulating the intestinal microbial composition.

Alcoholic liver injury is mainly caused by long-term excessive alcohol consumption and has become a global public threat to human health. It is well known that Ganoderma lucidum has excellent beneficial effects on liver function and lipid metabolism. The object of this study was to investigate the hepatoprotective effects of ganoderic acid A (GAA, one of the main triterpenoids in G. lucidum) against alcohol-induced liver injury and reveal the underlying mechanisms of its protective effects. The results showed that oral administration of GAA significantly inhibited the abnormal elevation of the liver index, serum total triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice exposed to alcohol intake, and also significantly protected the liver against alcohol-induced excessive lipid accumulation and pathological changes. Besides, alcohol-induced oxidative stress in the liver was significantly ameliorated by the dietary intervention of GAA through decreasing the hepatic levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA), and increasing hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and hepatic levels of glutathione (GSH). In addition, GAA intervention evidently ameliorated intestinal microbial disorder by markedly increasing the abundance of Muribaculaceae, Prevotellaceae, Jeotgalicoccus, Bilophila, Family_XIII_UCG_001, Aerococcus, Ruminococcaceae_UCG_005, Harryflintia, Christensenellaceae, Rumonpcpccaceae, Prevotelaceae_UCG_001, Clostridiales_vadinBB60_group, Parasutterella and Bifidobacterium, but decreasing the proportion of Lactobacillus, Burkholderia_Caballeroria_Paraburkholderia, Escherichia_Shigella and Erysipelatoclostridium. Furthermore, liver metabolomics based on UPLC-QTOF/MS demonstrated that oral administration of GAA had a significant regulatory effect on the composition of liver metabolites in mice exposed to alcohol intake, especially the levels of the biomarkers involved in the metabolic pathways of riboflavin metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, fructose and mannose metabolism. Moreover, dietary supplementation of GAA significantly regulated the hepatic mRNA levels of lipid metabolism and inflammatory response related genes. Conclusively, these findings demonstrate that GAA has beneficial effects on alleviating alcohol-induced liver injury and is expected to become a new functional food ingredient for the prevention of alcoholic liver injury.

Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake.

Alcoholic liver injury is mainly caused by excessive alcohol consumption and has become a global public health problem threatening human health. It is well known that Ganoderma lucidum possesses various excellent beneficial effects on liver function and lipid metabolism. The purpose of this study was to evaluate the underlying protective effect and action mechanism of ganoderic acids-rich G. lucidum ethanol extract (GLE) on alcohol-induced liver injury in mice with excessive alcohol intake. Results showed that oral administration of GLE could obviously inhibit the abnormal increases of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and also significantly protect the liver against alcohol-induced excessive hepatic lipid accumulation and pathological changes. In addition, alcohol-induced oxidative stress in liver was significantly ameliorated by the dietary intervention of GLE through reducing the hepatic levels of maleic dialdehyde (MDA) and lactate dehydrogenase (LDH), and increasing the hepatic levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and alcohol dehydrogenase (ADH). Compared with the model group, GLE intervention significantly ameliorated the intestinal microbial disorder by elevating the relative abundance of Ruminiclostridium_9, Prevotellaceae_UCG-001, Oscillibacter, [Eubacterium]_xylanophilum_group, norank_f_Clostridiates_vadinBB60_group, GCA-900066225, Bilophila, Ruminococcaceae_UCG-009, norank_f_Desulfovibrionaceae and Hydrogenoanaerobacterium, but decreasing the proportion of Clostridium_sensu_stricto_1. Furthermore, liver metabolomic profiling suggested that GLE intervention had a significant regulatory effect on the composition of liver metabolites in mice with excessive alcohol intake, especially the levels of some biomarkers involved in primary bile acid biosynthesis, riboflavin metabolism, tryptophan metabolism, biosynthesis of unsaturated fatty acids, fructose and mannose metabolism, glycolysis/gluconeogenesis. Additionally, dietary supplementation with GLE significantly regulated the mRNA levels of key genes related to fatty acids metabolism, ethanol catabolism and inflammatory response in liver. Conclusively, these findings indicate that GLE has a potentially beneficial effect on alleviating alcohol-induced liver injury and may be developed as a promising functional food ingredient.

Sparstolonin B suppresses free fatty acid palmitate-induced chondrocyte inflammation and mitigates post-traumatic arthritis in obese mice.

Abnormal lipid metabolism, such as systemic increased free fatty acid, results in overproduction of pro-inflammatory enzymes and cytokines, which is crucial in the development of obesity-related osteoarthritis (OA). However, there are only a few drugs that target the lipotoxicity of OA. Recent researches have documented that the traditional Chinese medicine, Sparstolonin B (Ssn B), exerted anti-inflammatory effects in various diseases, but not yet in OA. On the basis of this evidence, our works purposed to evaluate the effect of Ssn B on free fatty acid (FFA) palmitate (PA)-stimulated human osteoarthritic chondrocytes and obesity-associated mouse OA model. We found that Ssn B suppressed PA-triggered inflammatory response and extracellular matrix catabolism in a concentration-dependent approach. In vivo, Ssn B treatment inhibited cartilage degeneration and subchondral bone calcification caused by joint mechanical imbalance and alleviated metabolic inflammation in obesity. Mechanistically, co-immunoprecipitine and molecular docking analysis showed that the formation of toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) complex caused by PA was blocked by Ssn B. Subsequently, it leads to inactivation of PA-caused myeloid differentiation factor 88 (MyD88)-dependent nuclear factor-kappaB (NF-κB) cascade. Together, these findings demonstrated that Ssn B is a potential treatment agent for joint degenerative diseases in obese individuals.

Emodin induces apoptosis and suppresses non-small-cell lung cancer growth via downregulation of sPLA2-IIa.

BACKGROUND: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development. PURPOSE: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC). METHODS: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model. RESULTS: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle. CONCLUSION: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC.