Exploring the Potential Mechanisms of Action of Gentiana Veitchiorum Hemsl. Extract in the Treatment of Cholestasis using UPLC-MS/MS, Systematic Network Pharmacology, and Molecular Docking.

INTRODUCTION: Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine for treating hepatobiliary disease cholestasis. However, the mechanisms mediating its efficacy in treating cholestasis have yet to be determined. AIM: To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated approach combining ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with network pharmacology was established. MATERIALS AND METHODS: A comprehensive analysis of the chemical composition of GV was achieved by UPLC-MS/MS. Subsequently, a network pharmacology method that integrated target prediction, a protein-protein interaction (PPI) network, gene set enrichment analysis, and a component- target-pathway network was established, and finally, molecular docking and experiments in vitro were conducted to verify the predicted results. RESULTS: Twenty compounds that were extracted from GV were identified by UPLC-MS/MS analysis. Core proteins such as AKT1, TNF, and IL6 were obtained through screening in the Network pharmacology PPI network. The Kyoto Encyclopedia of the Genome (KEGG) pathway predicted that GV could treat cholestasis by acting on signaling pathways such as TNF/IL-17 / PI3K-Akt. Network pharmacology suggested that GV might exert a therapeutic effect on cholestasis by regulating the expression levels of inflammatory mediators, and the results were further confirmed by the subsequent construction of an LPS-induced RAW 264.7 cell model. CONCLUSIONS: In this study, UPLC-MS/MS analysis, network pharmacology, and experiment validation were used to explore potential mechanisms of action of GV in the treatment of cholestasis.

[Mechanism of Zhenwu Decoction in improving renal inflammatory injury in mice with DN of spleen-kidney Yang deficiency syndrome by regulating ROCK/IKK/NF-κB pathway].

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1ß, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1ß, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.

Prognostic role of vitamin D receptor in digestive system tumours: A systematic review and preliminary meta-analysis.

The prognostic value of vitamin D receptor (VDR) in a variety of digestive system tumours remains controversial. In view of this, we conducted a meta-analysis. Published studies (as of Mar 30, 2023) assessing the prognostic role of VDR in digestive system tumours were retrieved. Pooled analyses were conducted based on the hazard ratios (HRs) of high VDR expression extracted from the included studies. If heterogeneity was detected, the random-effects model was used; otherwise, the fixed-effects model was used. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. Eight studies with 3,109 patients were included. The pooled results indicated that patients with high VDR expression generally had better overall survival (OS) (pooled HR = 0.67; 95% CI = 0.53-0.85; P = 0.001). Subgroup analyses showed that tumour type was the variable affecting the association between VDR expression and OS. VDR expression in colorectal cancer was not associated with OS (pooled HR = 0.84; 95% CI = 0.68-1.03; P = 0.086). We eliminated publication bias using the "trim and fill" method and found that high VDR expression remained an indicator of good OS (P = 0.001). Only a few studies explored the relationship between VDR expression and cancer-specific survival (CSS) or progression-free survival (PFS), and the pooled results indicated no association between them (P>0.05). VDR expression is a prognostic indicator in digestive system tumours and may also be used as a reference for vitamin D supplementation. Detection of VDR expression not only helps to evaluate prognosis but also to formulate more precise treatment plans for patients with digestive system tumours.

Effects of dietary dandelion (Taraxacum mongolicum Hand.-Mazz.) polysaccharides on the performance and gut microbiota of laying hens.

This experiment was designed to evaluate the influences of dietary dandelion polysaccharides (DP) on the performance and cecum microbiota of laying hens. Three hundred laying hens were assigned to five treatment groups: the basal diet group (CK group), three DP groups (basal diets supplemented with 0.5, 1.0, and 1.5 % DP), and the inulin group (IN group, basal diet supplemented with 1.5 % inulin). Increased daily egg weight and a decreased feed conversion rate were observed when the diets were supplemented with inulin or DP. The calcium metabolism rate in the 0.5 % and 1.0 % DP groups was greater than that in the CK group. The DP groups increased the short-chain fatty acid concentration, decreased pH, and enhanced the relative abundances of Parabacteroides, Alloprevotella, and Romboutsia in the cecum. These results showed that DP supplementation in the diets of laying hens can improve their performance, which might be associated with the regulation of the cecal microbiota.

Yogurt Supplementation Attenuates Insulin Resistance in Obese Mice by Reducing Metabolic Endotoxemia and Inflammation.

BACKGROUND: Inflammation is an underlying mechanism for the development of obesity-related health complications. Yogurt consumption inhibits obesity-associated inflammation, but the tissue-specific mechanisms have not been adequately described. OBJECTIVES: We aimed to determine the tissue-specific responses by which yogurt supplementation inhibits inflammation. METHODS: C57BL/6 male mice (5 wk old) were fed a Teklad Global 14% Protein Rodent Maintenance diet as a control or a high-fat diet (60% calories from fat) to induce obesity for 11 wk, followed by feeding a Western diet (WD; 43% carbohydrate and 42% fat) or WD supplemented with 5.6% lyophilized yogurt powder for 3 wk to test for the impact of yogurt supplementation. Markers of metabolic endotoxemia and inflammation were assessed in plasma and tissues. Cecal and fecal microbiota were profiled by 16S rRNA sequencing. RESULTS: In obese mice, relative to the WD control group, yogurt supplementation attenuated HOMA-IR by 57% (P = 0.020), plasma TNF-α by 31% (P < 0.05) and colonic IFN-γ by 46% (P = 0.0034), which were accompanied by a 40% reduction in plasma LPS binding protein (LBP) (P = 0.0019) and 45% less colonic Lbp expression (P = 0.037), as well as alteration in the beta diversity of cecal microbiota (P = 0.0090) and relative abundance of certain cecal microbes (e.g., Lachnospiraceae Dorea longicatena with P = 0.049). There were no differences in the LBP, Lbp, and Cd14 levels in the liver and small intestine between obese mice with and without yogurt supplementation (P > 0.05). CONCLUSIONS: Yogurt consumption inhibits obesity-induced inflammation in mice by modulating colonic endotoxin detoxification, changing the gut microbiota, and improving glucose metabolism. This work helps to establish the underlying mechanisms by which yogurt consumption affects markers of metabolic and immune health.

New iridoids from Patrinia scabiosaefolia and their hypoglycemic effects by activating PI3K/Akt signaling pathway.

Growing in regions of Asia and North America, Patrinia scabiosaefolia is a wild vegetable and herb that has demonstrated health-promoting properties. Iridoids are one of the most bioactive phytochemicals in P. scabiosaefolia but the in-depth study is scarce. Herein we reported the separation and characterization of nine iridoids (compounds 1-9) from P. scabiosaefolia, and two compounds (2 and 6) were new. All the structures of the nine iridoids were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Compound 2 is a five-member ring iridoid, reminiscent of a broken C-1 and C-2 bond. Compound 6 has a typical monoene valerian iridoid, but the 5-deoxyglucose moiety at C-11 position is uncommon in this genus. The anti-diabetic evaluation of the isolated compounds revealed that compounds 1, 2, and 9 significantly increased the glucose absorption in 3 T3-L1 cells (P < 0.01). Further mechanism investigations have demonstrated that compound 1 promoted glucose uptake in dexamethasone-treated 3 T3-L1 adipocytes by activating PI3K/Akt signaling pathway. The expression of GLUT4 mRNA and protein was also upregulated. These results provide scientific references for the potential use of P. scabiosaefolia as a functional food to manage hyperglycemia.

Porphyrin-Based Nanoparticles: A Promising Phototherapy Platform.

Phototherapy, including photodynamic therapy and photothermal therapy, is an emerging form of non-invasive treatment. The combination of imaging technology and phototherapy is becoming an attractive development in the treatment of cancer, as it allows for highly effective therapeutic results through image-guided phototherapy. Porphyrins have attracted significant interest in the treatment and diagnosis of cancer due to their excellent phototherapeutic effects in phototherapy and their remarkable imaging capabilities in fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. However, porphyrins suffer from poor water solubility, low near-infrared absorption and insufficient tumor accumulation. The development of nanotechnology provides an effective way to improve the bioavailability, phototherapeutic effect and imaging capability of porphyrins. This review highlights the research results of porphyrin-based small molecule nanoparticles in phototherapy and image-guided phototherapy in the last decade and discusses the challenges and directions for the development of porphyrin-based small molecule nanoparticles in phototherapy.

Genome sequencing reveals chromosome fusion and extensive expansion of genes related to secondary metabolism in Artemisia argyi.

Artemisia argyi, as famous as Artemisia annua, is a medicinal plant with huge economic value in the genus of Artemisia and has been widely used in the world for about 3000 years. However, a lack of the reference genome severely hinders the understanding of genetic basis for the active ingredient synthesis of A. argyi. Here, we firstly report a complex chromosome-level genome assembly of A. argyi with a large size of 8.03 Gb, with features of high heterozygosity (2.36%), high repetitive sequences (73.59%) and a huge number of protein-coding genes (279 294 in total). The assembly reveals at least three rounds of whole-genome duplication (WGD) events, including a recent WGD event in the A. argyi genome, and a recent burst of transposable element, which may contribute to its large genome size. The genomic data and karyotype analyses confirmed that A. argyi is an allotetraploid with 34 chromosomes. Intragenome synteny analysis revealed that chromosomes fusion event occurred in the A. argyi genome, which elucidates the changes in basic chromosome numbers in Artemisia genus. Significant expansion of genes related to photosynthesis, DNA replication, stress responses and secondary metabolism were identified in A. argyi, explaining the extensive environmental adaptability and rapid growth characteristics. In addition, we analysed genes involved in the biosynthesis pathways of flavonoids and terpenoids, and found that extensive gene amplification and tandem duplication contributed to the high contents of metabolites in A. argyi. Overall, the reference genome assembly provides scientific support for evolutionary biology, functional genomics and breeding in A. argyi and other Artemisia species.

Comfrey polysaccharides modulate the gut microbiota and its metabolites SCFAs and affect the production performance of laying hens.

Effects of dietary supplementation of comfrey polysaccharides (CPs) on production performance, egg quality, and microbial composition of cecum in laying hens were evaluated. A total of 240 laying hens were allocated into 4 groups with 6 replicates per group. The laying hens were fed diets containing CPs at levels of 0, 0.5, 1.0, and 1.5 %, respectively. The results showed that the egg production rate increased by 5.97 %, the egg mass improved by 6.71 %, and the feed conversion rate reduced by 5.43 % in the 1.0 % supplementation group of CPs compared with those in the control group. The digestibility of ash, crude fat, and phosphorus was notably improved by the addition of CPs at 1.0 % (P < 0.05). The relative abundances of Bacteroidetes at the phylum level, Bacteroidaceae, Rikenellaceae, and Prevotellaceae at the family level were increased by CPs (P < 0.05). The relative abundances of Bacteroides, Megamonas, Rikenellaceae_RC9_gut_group, [Ruminococcus]_torques_group, Methanobrevibacter, Desulfovibrio, Romboutsia, Alistipes, and Intestinimonas at the genus level were increased by CPs (P < 0.05). Dietary supplementation of CPs could enhance the production performance of laying hens, which might be related to the improvement of nutrient digestibility and microbial community modulations in the cecum. Therefore, CPs have potential application value as prebiotics in laying hens.

Dietary herbaceous mixture supplementation reduced hepatic lipid deposition and improved hepatic health status in post-peak laying hens.

Fatty liver hemorrhagic syndrome is characterized by hepatic damage and hemorrhage impairing animal welfare in birds, which was well-known to be moderately relieved through dietary choline chloride supplementation in laying hens. Chinese herb has been proven to exert a positive role on hepatic health in human and rodents. Here, we investigated the effect of herbaceous mixture (HM), which consists of Andrographis paniculate, Silybum marianum, Azadirachta Indica, and Ocimum basilicum (2:3.5:1:2), on the hepatic lipid metabolism and health status in laying hens. A total of 240 Hy-line Brown hens (389-day-old) were randomly fed the basal diet with 0 mg/kg choline chloride (negative control, NC), 1,000 mg/kg choline chloride (control, Ctrl), or 300 mg/kg HM for 28 d. Birds fed HM diet exhibited lower serum triglyceride (TG) and low-density lipoprotein cholesterol concentration, and higher high-density lipoprotein cholesterol level than those received NC and Ctrl diets (P < 0.05). When compared to control and NC group, the diets with HM decreased the contents of total cholesterol and TG in liver, as well as upregulated the mRNA abundance of hepatic hormone-sensitive lipase and lipoprotein lipase. Meanwhile, the hepatic area and diameter of steatosis vacuoles were also decreased by dietary HM administration (P < 0.05), which accompanied by decreased serum alanine aminotransferase activity (P < 0.05). Birds fed HM diets enhanced the hepatic antioxidative capacity than those received NC and Ctrl diet. Dietary HM depressed the mRNA level of inflammatory cytokine as compared to NC but not Ctrl group. Collectively, the diet with 300 mg/kg HM has a favorable effect in decreasing the lipid deposition and protecting liver injury by alleviating hepatic oxidant stress and inflammation in post-peak laying hens.

Modified cystoscopy-assisted laparoscopic Y-V plasty for recalcitrant bladder neck contracture.

BACKGROUND AND AIM: Recalcitrant bladder neck contracture (BNC) is a common complication after transurethral resection of the prostate. Our aim was to show the outcomes of a modified cystoscopy-assisted laparoscopic Y-V plasty for BNC treatments. MATERIAL AND METHODS: We retrospectively evaluated a series of 27 patients who underwent a modified cystoscopy-assisted laparoscopic Y-V plasty for recalcitrant BNC from January 2017 to September 2019. Urinary flow rate, international prostate symptom score (IPSS), international index of erectile function-5 (IIEF-5) and bladder urethral examination by cystoscopy were performed preoperatively and postoperatively, respectively. RESULTS: All patients underwent the procedure successfully and no serious complication occurred. The median surgery time was 68.6 min without massive bleeding. The median follow-up time was 14.2 months and no patients had urinary incontinence. The maximum urine flow rate 3 months after surgery was significantly higher than prior to surgery (17.7 ± 2.1 ml/s vs. 8.2 ± 1.2 ml/s, p < 0.05). The IPSS was significantly decreased compared with the preoperative score (5.7 ± 2.3 vs. 19.2 ± 1.4, p < 0.05). The cystoscopy showed a wide bladder neck and the survival bladder flap in prostate urethral 3 months postoperatively in 92.6% (25/27) patients. CONCLUSIONS: The modified cystoscopy-assisted laparoscopic Y-V plasty is a feasible and effective technique for recalcitrant BNC treatment.

Evaluation of the effectiveness and safety of acupuncture in the treatment of premature ventricular contractions: A protocol for systematic review and meta-analysis.

BACKGROUND: Premature ventricular contractions are the most common type of arrhythmia. The clinical symptoms are mainly palpitations. In severe cases, syncope, angina pectoris and heart failure may occur, which seriously affect people's lives and ability to work. Antiarrhythmic drugs have many side effects and should not be taken for long periods. Acupuncture has a significant effect on the treatment of premature ventricular contractions. Therefore, to evaluate the effectiveness and safety of acupuncture in the treatment of premature ventricular contractions, we conducted this study, with the goal of providing a scientific methodology for this alternative treatment. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science Journal Database, and China Biomedical Literature Database. We selected all randomized clinical trials related to the use of acupuncture in the treatment of premature ventricular contractions published on or before October 10, 2021, and we will conduct literature screening and data extraction based on specific inclusion and exclusion criteria. We will use the bias risk assessment tool from the Cochrane Systematic Review Manual to evaluate the quality of the research selected for inclusion in our study. RevMan5.3 software will be used to perform statistical analysis on the data. RESULTS: The results of this study will provide evidence for the effectiveness and safety of acupuncture in the treatment of premature ventricular contractions. CONCLUSION: The purpose of this study is to explore the efficacy of acupuncture in the treatment of patients with premature ventricular contractions and to provide an effective reference for clinicians and patients on its use. INPLASY REGISTRATION NUMBER: INPLASY2021100040.

Genome-Wide Identification of CBL-CIPK Gene Family in Honeysuckle (Lonicera japonica Thunb.) and Their Regulated Expression Under Salt Stress.

In plants, calcineurin B-like proteins (CBLs) are a unique group of Ca2+ sensors that decode Ca2+ signals by activating a family of plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). CBL-CIPK gene families and their interacting complexes are involved in regulating plant responses to various environmental stimuli. To gain insight into the functional divergence of CBL-CIPK genes in honeysuckle, a total of six LjCBL and 17 LjCIPK genes were identified. The phylogenetic analysis along with the gene structure analysis divided both CBL and CBL-interacting protein kinase genes into four subgroups and validated by the distribution of conserved protein motifs. The 3-D structure prediction of proteins shown that most LjCBLs shared the same Protein Data Bank hit 1uhnA and most LjCIPKs shared the 6c9Da. Analysis of cis-acting elements and gene ontology implied that both LjCBL and LjCIPK genes could be involved in hormone signal responsiveness and stress adaptation. Protein-protein interaction prediction suggested that LjCBL4 is hypothesized to interact with LjCIPK7/9/15/16 and SOS1/NHX1. Gene expression analysis in response to salinity stress revealed that LjCBL2/4, LjCIPK1/15/17 under all treatments gradually increased over time until peak expression at 72 h. These results demonstrated the conservation of salt overly sensitive pathway genes in honeysuckle and a model of Ca2+-LjCBL4/LjSOS3-LjCIPK16/LjSOS2 module-mediated salt stress signaling in honeysuckle is proposed. This study provides insight into the characteristics of the CBL-CIPK gene families involved in honeysuckle salt stress responses, which could serve as a foundation for gene transformation technology, to obtain highly salt-tolerant medicinal plants in the context of the global reduction of cultivated land.

Origanum majorana L.: A Nutritional Supplement With Immunomodulatory Effects.

Origanum majorana L. is an aromatic herb that has been grown in several Mediterranean countries since ancient times, but became popular during the Middle Ages as a medicinal plant and seasoning ingredient. O. majorana has many pharmacological effects, but its immunoreactive components and mechanisms are still unclear. In this study, four compounds were isolated and identified from O. majorana by a spectral analysis, including 1H and 13C-NMR. They were 1H-indole-2-carboxylic acid (1), (+)-laricresol (2), (+)-isolaricresol (3), and procumboside B (4, pB), which were isolated for the first time in O. majorana. The immunomodulatory effects of the four compounds were screened, and pB had good immunomodulatory activity on RAW 264.7 cells. The immunomodulatory mechanism of pB was proved, in which pB could increase the secretion of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) and simultaneously upregulate the expression of CD80 and CD86 on the cell surface. These results suggested that the mechanism of pB may be related to the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs)-signaling pathways. O. majorana is rich in nutrients and is commonly used in diets, so it can be used as a nutritional supplement with immunomodulatory effects.

Molecular Heterogeneity in Localized Diffuse Large B-Cell Lymphoma.

The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network-International Prognostic Index. According to the molecular features, increased MPEG1 mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-ß signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase >3 upper limit of normal was an independent adverse prognostic factor for OS, and ATM mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.

Adequacy of calcium and vitamin D reduces inflammation, ß-catenin signaling, and dysbiotic Parasutterela bacteria in the colon of C57BL/6 mice fed a western-style diet.

Adoption of an obesogenic diet low in calcium and vitamin D (CaD) leads to increased obesity, colonic inflammation, and cancer. However, the underlying mechanisms remain to be elucidated. We tested the hypothesis that CaD supplementation (from inadequacy to adequacy) may reduce colonic inflammation, oncogenic signaling, and dysbiosis in the colon of C57BL/6 mice fed a Western diet. Male C57/BL6 mice (4-weeks old) were assigned to 3 dietary groups for 36 weeks: (1) AIN76A as a control diet (AIN); (2) a defined rodent "new Western diet" (NWD); or (3) NWD with CaD supplementation (NWD/CaD). Compared to the AIN, mice receiving the NWD or NWD/CaD exhibited more than 0.2-fold increase in the levels of plasma leptin, tumor necrosis factor α (TNF-α) and body weight. The levels of plasma interleukin 6 (IL-6), inflammatory cell infiltration, and ß-catenin/Ki67 protein (oncogenic signaling) were increased more than 0.8-fold in the NWD (but not NWD/CaD) group compared to the AIN group. Consistent with the inflammatory phenotype, colonic secondary bile acid (inflammatory bacterial metabolite) levels increased more than 0.4-fold in the NWD group compared to the NWD/CaD and AIN groups. Furthermore, the abundance of colonic Proteobacteria (e.g., Parasutterela), considered signatures of dysbiosis, was increased more than four-fold; and the α diversity of colonic bacterial species, indicative of health, was decreased by 30% in the NWD group compared to the AIN and NWD/CaD groups. Collectively, CaD adequacy reduces colonic inflammation, ß-catenin oncogenic signaling, secondary bile acids, and bacterial dysbiosis in mice fed with a Western diet.

A rapid method and mechanism to identify the active compounds in Malus micromalus Makino fruit with spectrum-effect relationship, components knock-out and molecular docking technology.

Fingerprints of 20 batches of Malus micromalus Makino fruit were established by HPLC coupled with hierarchical cluster analysis (HCA) and principal component analysis (PCA) to estimate the common peaks on the basis of traditional similarity evaluation methods. Chromatographic peaks were identified as p-coumaric acid (P2), ferulic acid glycoside (P6), 4-O-ß-Glucopyranosyl-cis-coumaric acid (P8), phloretin-2'-xyloglucoside (P10), phloridzin (P11) and quercetin-3-O-α-rhamnoside (P12) by UPLC-MS/MS method. The results of tyrosinase kinetics experiments showed that: P2 and the concentration of P11 was greater than 0.50 mmol/L mainly had a competitive inhibitory effect on tyrosinase, and the concentration of phlorizin was less than at 0.25 mmol/L, it has a mixed inhibitory effect. P8 was mainly a non-competitive activation type in the concentration range, while P12 was a mixed activation type. The results of tyrosinase molecular docking showed that: P2, P8, P11, P12 was located in the active center of the hydrophobic pocket of the enzyme. They bound to tyrosinase residues by hydrogen bonds and interacted with many hydrophobic residues around them to maintain the structure of the complex. This research provides a rapid method to determine the active compounds in edible plants with the technology of spectrum-effect relationship, component knock-out and molecular docking.

The NF-[Formula: see text]B Signaling and Wnt/[Formula: see text]-catenin Signaling in MCF-7 Breast Cancer Cells in Response to Bioactive Components from Mushroom Antrodia Camphorata.

Breast cancer is the leading cancer, accounting for approximately 15% cancer deaths in women worldwide. This study investigated the anti-inflammation and anticancer properties of two bioactive components from Antrodia camphorata(AC), a rare medicinal mushroom natively grown in Taiwan and commonly used in Chinese traditional medicine. The anti-inflammatory and antitumorigenic functions of Antroquinonol (AQ) and 4-Acetylantroquinonol B (4-AAQB) from AC were examined on breast cancer cell line MCF-7 with/without TNF-[Formula: see text] stimulation. Among nine inflammatory mediators (IL6, IL10, IL1[Formula: see text], IFN[Formula: see text], PTGS2, TGF[Formula: see text]1, TNF-[Formula: see text], CCL2 andCSF1) examined, AQ inhibited two of them (IL-10 and PTGS2), while 4-AAQB inhibited three of them (IL-10, PTGS2 andTNF-[Formula: see text] ([Formula: see text]¡ 0.05). TNF-[Formula: see text] stimulated expressions of five mediators (IL6, IL10, IFN[Formula: see text], PTGS2, and CCL2), and AQ and 4-AAQB inhibited IL6 elevation ([Formula: see text]¡ 0.05). Both components inhibited aromatase expression with/without TNF-[Formula: see text] stimulation, with 4-AAQB to be more effective ([Formula: see text]¡ 0.05). For immune checkpoint CD47, both components inhibited CD47 expression ([Formula: see text]¡ 0.05), but it did not respond to TNF-[Formula: see text] stimulation. For Wnt/[Formula: see text]- catenin signaling downstream genes (CCND1, C-MYC and AXIN2), both components have significant or marginal inhibitory effect on C-MYC in the condition with/without TNF-[Formula: see text] stimulation. The luciferase assay demonstrated that both components exhibited inhibitory effect on NF-[Formula: see text]B signaling and Wnt/[Formula: see text]-catenin signaling in the condition without TNF-[Formula: see text] stimulation. In conclusion, our results displayed an overall pattern that AQ and 4-AAQB possess potential anti-inflammatory and antitumorigenic functions in MCF-7 breast cancer cells and warranted further in vivo pre-clinical and clinical studies to explore their anticancer properties.

Natural Products: Review for Their Effects of Anti-HBV.

Hepatitis B is a global infectious disease, seriously endangering human health. Currently, there are mainly interferons and nucleoside analogues treatment of hepatitis B in the clinic, which have certain therapeutic effects on hepatitis B, but their side effects and drug resistance are increasingly prominent. Therefore, it is urgently needed to discover and develop new anti-HBV drugs, especially natural products, which have novel, high efficiency, and low toxicity anti-HBV compounds with novel antiviral mechanisms. In this manuscript, the natural products (polysaccharides and 165 compounds) with the activity of antihepatitis B virus are discussed according to their chemical classes, including 14 phenylpropanoids, 8 flavonoids,12 xanthones, 13 anthroquinones, 47 terpenoids, 6 alkaloids, 15 enediynes, 11 aromatics, 18 phenylalanine dipeptides compounds, and 13 others. In addition, the anti-HBV mechanism and targets of natural product were also discussed. The aim of this review is to report new discoveries about anti-HBV natural products and to provide reference for researchers.

Anti-Hepatoma Compound Determination by the Method of Spectrum Effect Relationship, Component Knock-Out, and UPLC-MS2 in Scheflera heptaphylla (L.)Frodin Harms and Its Mechanism.

Scheflera heptaphylla (L.)Frodin, a kind of Traditional Chinese Medicine, is commonly used in anti-inflammatory, analgesic, anti-viral, anti-tumor, and hemostasis. This study aimed to determine the anti-hepatoma components and its mechanism from the leaves of S. heptaphylla. The spectrum-effect relationships were analyzed by the method of Partial least squares, indicating that P1, P2, and P10 were positively correlated to inhibitory activity of Huh7 cells. Whereas others were negatively correlated. The technologies of component knock-out and UPLC-MS2 were used to determine compounds as 3,4-Dicaffeoylquinic acid (P6), 3,5-Dicaffeoylquinic acid (P7), 3α-Hydroxy-lup-20(29)-ene-23,28-dioic acid (P10, named Compound A). The results forecasted that Compound A had the best correlation with inhibitory activity. The effects of Compound A on the activities of human hepatoma cells (Huh7, SMMC-7721, HepG 2) and normal hepatocytes (L0-2, Chang liver) were evaluated. Cell apoptosis was observed with inverted microscope and flow cytometer. In addition, the proteins, related to apoptosis, were detected by Western blot. The results showed that Compound A (400 nM) could significantly inhibit the activity of three hepatoma cells (P < 0.001) with slight toxicity to normal hepatocytes, and the IC50 values were 285.3 and 315.1 nM, respectively, which were consistent with the prediction of spectrum-effect relationships. After treatment with Compound A, the number of hepatoma cells decreased significantly. And the apoptosis rate of Huh7 cells increased significantly (P < 0.001) in Compound A (200, 400 nM) groups, SMMC-7721 and HepG 2 were directly necrotic. Compound A groups could significantly improve the level of intracellular reactive oxygen species (ROS) (P < 0.05, P < 0.001) in Huh7 with no effect on normal hepatocytes. The content of apoptotic protein (Bax and Bim) in mitochondria was significantly increased in Compound A groups (P < 0.001). On the contrary, the content of anti-apoptotic protein (Bcl-xL and Mcl-1) decreased significantly (P < 0.001). These results demonstrated that Compound A was the main anti-hepatoma active component in the S. heptaphylla leaves. It achieved the effect of promoting apoptosis of Huh7 cells by regulating the levels of ROS and Bcl-2 family protein in mitochondrial apoptosis pathway.