Synthesis of Taxifolin-Loaded Polydopamine for Chemo-Photothermal-Synergistic Therapy of Ovarian Cancer.

Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.

The zhuyu pill relieves rat cholestasis by regulating the mRNA expression of lipid and bile metabolism associated genes.

Background: The Zhuyu pill (ZYP), composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, is an effective traditional Chinese medicine with potential anti-cholestatic effects. However, the underlying mechanisms of ZYP remain unknown. Objective: To investigate the mechanism underlying the interventional effect of ZYP on mRNA-seq analysis in cholestasis rat models. Materials and methods: This study tested the effects of a low-dose (0.6 g/kg) and high-dose (1.2 g/kg) of ZYP on a cholestasis rat model induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg). Serum biochemistry and histopathology results were used to evaluate the therapeutic effect of ZYP, and mRNA-Seq analysis was performed and verified using real-time fluorescence quantitative PCR (qRT-PCR). GO, KEGG, and GSEA analyses were integrated to identify the mechanism by which ZYP impacted cholestatic rats. Results: ZYP was shown to significantly improve abnormal changes in the biochemical blood indexes and liver histopathology of cholestasis rats and regulate pathways related to bile and lipid metabolism, including fatty acid metabolism, retinol metabolism, and steroid hormone biosynthesis, to alleviate inflammation, cholestasis, and lipid metabolism disorders. Relative expression of the essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, and Sult2a1 was verified by qRT-PCR and showed the same trend as mRNA-seq analysis. Conclusion: ZYP has a significant anti-cholestatic effect by regulating bile metabolism and lipid metabolism related pathways. These findings indicate that ZYP is a novel and promising prospect for treating cholestasis.

Research progress of natural plant polysaccharides inhibiting inflammatory signaling pathways and regulating intestinal flora and metabolism to protect inflammatory bowel disease.

Natural plant polysaccharides are macromolecular substances with a wide range of biological activities. They have a wide range of biological activities, especially play an important role in the treatment of inflammatory bowel disease. The molecular weight of polysaccharides, the composition of monosaccharides and the connection of glycosidic bonds will affect the therapeutic effect on inflammatory bowel disease. Traditional Chinese medicine plant polysaccharides and various types of plant polysaccharides reduce the levels of inflammatory cytokines IL-1ß, IL-6, IL-8 and IL-17, increase the level of anti-inflammatory factor IL-10, regulate NF-κB signaling pathway, and NLRP3 inflammasome to relieve colitis. At the same time, they can play a protective role by regulating the balance of intestinal flora in mice with colitis and increasing the abundance of probiotics to promote the metabolism of polysaccharide metabolites SCFAs. This review summarizes the research on the treatment of inflammatory bowel disease by many natural plant polysaccharides, and provides a theoretical basis for the later treatment of polysaccharides on inflammatory bowel disease.

Polysaccharide-based hydrogel promotes skin wound repair and research progress on its repair mechanism.

Polysaccharides, being a natural, active, and biodegradable polymer, have garnered significant attention due to their exceptional properties. These properties make them ideal for creating multifunctional hydrogels that can be used as wound dressings for skin injuries. Polysaccharide hydrogel has the ability to both simulate the natural extracellular matrix, promote cell proliferation, and provide a suitable environment for wound healing while protecting it from bacterial invasion. Polysaccharide hydrogels offer a promising solution for repairing damaged skin. This review provides an overview of the mechanisms involved in skin damage repair and emphasizes the potential of polysaccharide hydrogels in this regard. For different skin injuries, polysaccharide hydrogels can play a role in promoting wound healing. However, we still need to conduct more research on polysaccharide hydrogels to provide more possibilities for skin damage repair.

Research Progress on Extraction, Isolation, Structural Analysis and Biological Activity of Polysaccharides from Panax Genus.

The panax genus is a widely used medicinal plant with good biological activity. As one of the main active components of the Panax genus, polysaccharides have various pharmacological effects. This review summarizes the latest research reports on ginseng, American ginseng, and Panax notoginseng polysaccharides and compares the differences in extraction, isolation and purification, structural characteristics, and biological activities. The current research mainly focuses on ginseng polysaccharides, and the process of extraction, isolation, and structure analysis of each polysaccharide is roughly the same. Modern pharmacological studies have shown that these polysaccharides have antioxidants, antitumor, immunomodulatory, antidiabetic, intestinal protection, skin repair, and other biological activities. This review provides new insights into the differences between the three kinds of ginseng polysaccharides which will help to further study the medicinal value of ginseng in traditional Chinese medicine.

Artemisia anomala S. Moore: A review of botany, traditional uses, phytochemistry, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia anomala S. Moore (family: Asteraceae) is a traditional herb that has been used for medicinal purposes in China for more than 1300 years. In traditional and local medicine, A. anomala is widely used in the treatment of rheumatic, dysmenorrhea, enteritis, hepatitis, hematuria and burn injury, and it is also considered as a natural botanical supplement in some areas, a traditional herb with both medicinal and edible properties. AIM OF THE REVIEW: The paper aims to provide a comprehensive overview of A. anomala, covering its botany, traditional uses, phytochemistry, pharmacological activity, and quality control, and to summarize the current research status in order to better understand the application value of A. anomala as a traditional herbal medicine and provide references for its further development and utilization. MATERIALS AND METHODS: The relevant information on A. anomala was collected by searching a range of literature and electronic databases using "Artemisia anomala" as the key search term. These sources included both ancient and modern books, the Chinese Pharmacopoeia, as well as various online databases such as PubMed, ScienceDirect, Wiley, ACS, CNKI, Springer, Taylor & Francis, Web of Science, Google Scholar, and Baidu Scholar. RESULTS: At present, 125 compounds have been isolated from A. anomala, including terpenoids, triterpenoids, flavonoids, phenylpropanoids, volatile oils and other compounds. Modern studies have confirmed that these active components have significant pharmacological activities, including anti-inflammatory, anti-bacterial, hepatoprotective, anti-platelet aggregation and anti-oxidation. In modern clinic, A. anomala is widely used in the treatment of rheumatoid arthritis, dysmenorrhea, irregular menstruation, traumatic bleeding, hepatitis, soft tissue contusion, burn and scald. CONCLUSIONS: Long-term traditional medicinal history and a large number of modern in vitro and in vivo studies have confirmed that A. anomala has a wide range of biological activities, which can provide rich resources for the discovery of promising drug candidates and the development of new plant supplements. However, the research on the active components and molecular mechanism of A. anomala is insufficient, and more mechanism-based pharmacological evaluation and clinical research should be carried out to provide a more powerful scientific basis for its traditional use. In addition, the index components and determination standards of A. anomala should be established as soon as possible, so as to establish a systematic and effective quality control system.

The application of Tong-fu therapeutic method on ulcerative colitis: A systematic review and meta-analysis for efficacy and safety of rhubarb-based therapy.

Background: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. Method: Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). Results: A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1ß expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. Conclusion: Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1-13 weeks or 3 months via administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.

Renshen Baidu Powder Attenuated Intestinal Inflammation and Apoptosis in Ulcerative Colitis Rats through the Inhibition of PI3K/AKT/NF-κB Signaling Pathway.

Objective: Renshen Baidu Powder (RBP) is a famous classic compound of traditional Chinese medicine (TCM) and is commonly used for treating ulcerative colitis (UC). However, the pharmacological mechanism of RBP in treating UC remains unclear. This study investigates the possible mechanism of RBP for UC treatment by network pharmacological analysis and rat validation. Methods: First, the main chemical constituents of RBP were identified using ultrahigh-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Then, we obtained targets of identified compounds from the SwissTargetPrediction database and targets associated with UC from GeneCards database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by RBP. Hematoxylin-eosin (HE) staining was used to observe the pathological change of colon in UC rats after treating RBP, and terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP Nick end labeling (TUNEL) staining was used to detect apoptosis after RBP treatment. The enzyme-linked immunosorbent assay (ELISA) was employed to evaluate cytokine levels of TNF-α, IL-1ß, and IL-6. The protein expressions of Bax, Bcl-2, PI3K, AKT, and NF-κB in colonic tissue were detected using immunohistochemistry (IHC). Real-time quantitative polymerase chain reaction (RT-QPCR) was employed to evaluate mRNA expression of PI3K, AKT, and NF-κB. Results: We found a total of 24 main compounds and 329 potential targets related to UC. According to KEGG results, 3 main pathways were identified as responsible for UC, including PI3K-AKT, HIF-1, and VEGF signaling pathway. Animal experiments showed that RBP treatment significantly attenuated colon damage in rats with UC. Mechanistically, RBP could inhibit PI3K/AKT/NF-κB pathway; decrease cell apoptosis; and downregulate the expression of TNF-α, IL-1ß, and IL-6. Conclusions: This study demonstrated that RBP may exert anti-inflammatory and antiapoptotic therapeutic benefits in UC by regulating the PI3K/AKT/NF-κB signaling pathways, providing a scientific basis for understanding the mechanism of RBP against UC.

Silk protein/polyvinylpyrrolidone nanofiber membranes loaded with puerarin accelerate wound healing in mice by reducing the inflammatory response.

In modern clinical applications, wound healing remains a considerable challenge. Excessive inflammatory response is associated with delayed wound healing. In this study, we prepared composite nanofibrous membranes by mixing the Chinese herbal extract puerarin (PUE) with natural silk protein (SF) and synthetic polymer polyvinylpyrrolidone (PVP) using electrostatic spinning technique, and conducted a series of studies on the structural and biological properties of the fibrous membranes. The results showed that the loading of PUE increased the diameter, porosity and hydrophilicity of nanofibers, which were more favorable for cell adhesion and proliferation. ABTS radical scavenging assay also showed that the loading of PUE enhanced the antioxidant properties of the fibrous membranes. In addition, SF/PVP/PUE nanofibers are non-toxic and can be used as wound dressings. In vitro experiments showed that SF/PVP/PUE nanofibers could effectively alleviate lipopolysaccharide (LPS)-induced inflammation in Immortalized human keratinocytes (HaCaT) cells and down-regulate pro-inflammatory cytokine expression in cells. In vivo studies further showed that the SF/PVP/PUE nanofibers could effectively accelerate wound repair. The mechanism is that SF/PVP/PUE nanofibers can inhibit the activation and transduction of toll-like receptor 4/myeloid differentiation factor88/nuclear factor kappa B (TLR4/MyD88/NF-κB) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways, thereby reducing the inflammatory response and achieving wound healing.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.

Objectives: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the gastrointestinal tract, and its prevalence is increasing worldwide. Fecal microbiota transplantation (FMT) is an emerging therapy that modifies the patient's gut microbiota by transplanting feces from a healthy donor to achieve disease remission. However, its efficacy and safety need to be further investigated. Methods: PubMed, the Cochrane Library, Web of Science, Embase, and Google Scholar databases (up to 8th November 2021) were searched and literature was screened by title and abstract as well as full text. The primary outcome was clinical remission, with the clinical response as a secondary outcome. Risk ratios (RR) with 95% confidence intervals (CI) were reported. Results: A total of 14 trials were included in this study. In terms of clinical remission, FMT had a significant effect compared to placebo (RR = 1.44, 95 CI%: 1.03 to 2.02, I 2 = 38%, P=0.03), with no significant risk of study heterogeneity. Moreover, FMT led to significant results in clinical response compared to placebo with moderate between-study heterogeneity (RR = 1.34, 95 CI%: 0.92 to 1.94, I 2 = 51%, P=0.12). Subgroup analysis showed a higher clinical remission for fresh fecal FMT (40.9%) than that for frozen fecal FMT (32.2%); the efficacy of gastrointestinal (GI) pretreatment, the severity of disease, route of administration, and the donor selection remain unclear and require more extensive study. Safety analysis concluded that most adverse events were mild and self-resolving. The microbiological analysis found that the patient's gut microbiota varied in favor of the donor, with increased flora diversity and species richness. Conclusion: FMT is a safe, effective, and well-tolerated therapy. Studies have found that fresh fecal microbiota transplant can increase clinical remission rates. However, more randomized controlled trials and long-term follow-ups are needed to assess its long-term effectiveness and safety.

An Integrated Approach Based on Network Analysis Combined With Experimental Verification Reveals PI3K/Akt/Nrf2 Signaling Is an Important Way for the Anti-Myocardial Ischemia Activity of Yi-Qi-Tong-Luo Capsule.

Background: Yiqi-Tongluo Capsule (YTC) is a Chinese traditional patent medicine that has been used in the treatment of myocardial ischemia (MI). However, its molecular mechanisms against MI have not been clear. Methods: Network analysis and experimental verification were used to explore the potential molecular mechanisms of YTC for MI treatment. Firstly, the main components in the capsules and the potential targets of these components were predicted by online databases. The MI related genes were collected from Genecards and Online Mendelian Inheritance in Man (OMIM) databases. The drug targets and disease targets were intersected, and then the protein-protein interaction (PPI) and Drug-Molecular-Target-Disease Network (DMTD) were constructed, and GO enrichment analysis and KEGG pathway enrichment analysis were performed. Based on the H2O2-stimulated H9c2 cells, flow cytometry, western blot (WB) and immunofluorescence experiments were performed to verify the network analysis prediction. Results: A total of 100 active components and 165 targets of YTC were predicted, in which there were 109 targets intersected with the targets of MI. GO and KEGG analysis showed that these potential targets were related to a variety of biological processes and molecular mechanisms, including oxidative stress and PI3K/AKT pathway. Astragaloside IV (AS IV) and paeoniflorin (PAE) might be the main active components in YTC. The results of cell counting kit-8 (CCK-8) showed that YTC alleviated the damage of H2O2 to H9c2 cells. The results of flow cytometry, DAPI staining and JC-1 probe showed that YTC alleviated H2O2 induced apoptosis in H9c2 cells. In addition, YTC reduced the level of intracellular superoxide anion, increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA) in H2O2-induced H9c2 cells. The results of immunofluorescence and WB showed that the phosphorylation of PI3K and Akt were increased, the expression of Bcl-2 was up-regulated and the expression of cleaved caspase-3 and Bax were down-regulated. Besides, the nuclear translocation of Nrf2 were increased. Conclusion: In conclusion, the results of this study showed that YTC might alleviate MI by suppressing apoptosis induced by oxidative stress via the PI3K/Akt/Nrf2 signal pathway.

Red ginseng has stronger anti-aging effects compared to ginseng possibly due to its regulation of oxidative stress and the gut microbiota.

BACKGROUND: Panax ginseng (PG) and red ginseng (RG) are considered to be effective anti-aging treatments. However, evidence of their therapeutic mechanisms and difference in anti-aging effects is lacking. PURPOSE: To explore the potential therapeutic mechanisms of RG and PG in brain damage in D-Gal-induced aging mice, and evaluate the difference in anti-aging effects caused by their compositional differences. METHODS: We first tested the chemical components in PG and RG. In D-Gal aging mouse model, RG and PG (800 mg/kg) were orally administered for 9 weeks. The mice performed the Radial Arm Maze (RAM) behavior test. We collected blood, brain tissue, and fecal samples and performed biochemical analysis, histological examination, western blot, and Illumina MiSeq sequencing analysis. RESULTS: The results of component analysis showed that the total polyphenols and rare ginsenosides were present in RG in 3.2, and 2.2 fold greater concentrations, respectively, compared to PG, while the proportion of non-starch polysaccharides in the crude polysaccharides of RG was 1.94 fold greater than that of PG. In D-Gal-induced aging mice, both PG and RG could prevent the increase in acetylcholinesterase (AChE), and malondialdehyde (MDA) levels, and improved the expression of superoxide dismutase (SOD), and catalase (CAT) in the serum. Meanwhile, both PG and RG could ameliorate brain tissue architecture and behavioral trial. In addition, the D-Gal-induced translocation of nuclear factor-κB (NF-κB), as well as activation of the pro-apoptotic factors Caspase-3 and the PI3K/Akt pathways were inhibited by PG and RG. Overall, both PG and RG exerted anti-aging effects, with RG stronger than PG. Finally, although both PG and RG regulated the diversity of gut microbes, RG appeared to aggravate the increase in probiotics, such as Bifidobacterium and Akkermania, and the decrease in inflammatory bacteria to a greater extent compared to PG. CONCLUSION: Our results suggest that RG is more conducive to delay the D-Gal-induced aging process than PG, with possible mechanisms including beneficial changes in brain structure, cognitive functions, oxidative stress inhibition, and gut microbiome structure and diversity than PG, These mechanisms may rely on the presence of more total polyphenols, rare ginsenosides and non-starch polysaccharides in RG.

Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota.

Aronia melanocarpa is a natural medicinal plant that has a variety of biological activities, its fruit is often used for food and medicine. Aronia melanocarpa polysaccharide (AMP) is the main component of the Aronia melanocarpa fruit. This research evaluated the delay and protection of AMP obtained from Aronia melanocarpa fruit on aging mice by D-Galactose (D-Gal) induction and explored the effect of supplementing AMP on the metabolism of the intestinal flora of aging mice. The aging model was established by intraperitoneal injection of D-Gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks. AMP (100 and 200 mg/kg) was given daily by oral gavage after 6 weeks of D-Gal-induced. The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice determined by the eight-arm maze test. H&E staining showed that AMP significantly reversed brain tissue pathological damage and structural disorders. AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family. Importantly, 16S rDNA analysis indicated the AMP treatment significantly retarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammation and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.

Efficacy-specific herbal group detection from traditional Chinese medicine prescriptions via hierarchical attentive neural network model.

BACKGROUND: Mining massive prescriptions in Traditional Chinese Medicine (TCM) accumulated in the lengthy period of several thousand years to discover essential herbal groups for distinct efficacies is of significance for TCM modernization, thus starting to draw attentions recently. However, most existing methods for the task treat herbs with different surface forms orthogonally and determine efficacy-specific herbal groups based on the raw frequencies an herbal group occur in a collection of prescriptions. Such methods entirely overlook the fact that prescriptions in TCM are formed empirically by different people at different historical stages, and thus full of herbs with different surface forms expressing the same material, or even noisy and redundant herbs. METHODS: We propose a two-stage approach for efficacy-specific herbal group detection from prescriptions in TCM. For the first stage we devise a hierarchical attentive neural network model to capture essential herbs in a prescription for its efficacy, where herbs are encoded with dense real-valued vectors learned automatically to identify their differences on the semantical level. For the second stage, frequent patterns are mined to discover essential herbal groups for an efficacy from distilled prescriptions obtained in the first stage. RESULTS: We verify the effectiveness of our proposed approach from two aspects, the first one is the ability of the hierarchical attentive neural network model to distill a prescription, and the second one is the accuracy in discovering efficacy-specific herbal groups. CONCLUSION: The experimental results demonstrate that the hierarchical attentive neural network model is capable to capture herbs in a prescription essential to its efficacy, and the distilled prescriptions significantly could improve the performance of efficacy-specific herbal group detection.

Gancao Xiexin decoction combined with mesalazine in the treatment of ulcerative colitis: A protocol for a systematic review and meta-analysis.

BACKGROUD: Ulcerative colitis (UC) is a chronic inflammatory disease that involves the rectum, colon and ileum. Gancao Xiexin decoction (GCXXD) is a classic herbal formula in Shanghanlun. More and more research evidence shows that GCXXD has a certain therapeutic effect on UC. Therefore, we designed this study protocol aim to evaluate the efficacy and safety of GCXXD combine with mesalazine for UC. METHODS: We will systematically search 6 databases, including PubMed, the Cochrane Library, EMBASE, CNKI, VIP, Wang-fang database up to July 2020 to obtain eligible studies. The primary outcomes will focus on the clinical effectiveness. Review Manager 5.3 software will be used for data analysis. RESULTS: This study will provide the systematic evidence of UC treated with GCXXD combine with mesalazine. CONCLUSION: The findings of this meta-analysis will provide evidence to judge whether GCXXD combine with mesalazine is a more effective intervention compare to mesalazine only for patient of UC. INPLASY REGISTRATION NUMBER: INPLASY202080008.

Identification of hub genes and small molecule therapeutic drugs related to breast cancer with comprehensive bioinformatics analysis.

Breast cancer is one of the most common malignant tumors among women worldwide and has a high morbidity and mortality. This research aimed to identify hub genes and small molecule drugs for breast cancer by integrated bioinformatics analysis. After downloading multiple gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, 283 overlapping differentially expressed genes (DEGs) significantly enriched in different cancer-related functions and pathways were obtained using LIMMA, VennDiagram and ClusterProfiler packages of R. We then analyzed the topology of protein-protein interaction (PPI) network with overlapping DEGs and further obtained six hub genes (RRM2, CDC20, CCNB2, BUB1B, CDK1, and CCNA2) from the network via STRING and Cytoscape. Subsequently, we conducted genes expression verification, genetic alterations evaluation, immune infiltration prediction, clinicopathological parameters analysis, identification of transcriptional and post-transcriptional regulatory molecules, and survival analysis for these hub genes. Meanwhile, 29 possible drug candidates (e.g., Cladribine, Gallium nitrate, Alvocidib, 1ß-hydroxyalantolactone, Berberine hydrochloride, Nitidine chloride) were identified from the DGIdb database and the GSE85871 dataset. In addition, some transcription factors and miRNAs (e.g., E2F1, PTTG1, TP53, ZBTB16, hsa-miR-130a-3p, hsa-miR-204-5p) targeting hub genes were identified as key regulators in the progression of breast cancer. In conclusion, our study identified six hub genes and 29 potential drug candidates for breast cancer. These findings may advance understanding regarding the diagnosis, prognosis and treatment of breast cancer.

Antidiabetic Effects of Arginyl-Fructosyl-Glucose, a Nonsaponin Fraction from Ginseng Processing in Streptozotocin-Induced Type 2 Diabetic Mice through Regulating the PI3K/AKT/GSK-3ß and Bcl-2/Bax Signaling Pathways.

Streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) caused insulin secretion disorder and hyperglycemia, further causing tissue and organ damage. In recent years, studies on ginseng (Panax ginseng C. A. Meyer) and its saponins (Ginsenosides) have proved to possess antidiabetic pharmacological activities, but the mechanism of nonsaponins on STZ-induced T2DM is still unclear. Arginyl-fructosyl-glucose (AFG) is a representative nonsaponin component produced in the processing of red ginseng. The present study was designed to assess the possible healing consequence of AFG on STZ-induced T2DM in mice and also to explore its fundamental molecular contrivances. T2DM-related indexes, fasting blood glucose levels, and body weight, histological changes, biochemical considerations, biomarkers, the mRNA countenance intensities of inflammatory facts, and variations in correlated protein manifestation in adipose tissue and liver tissue were calculated. Consequences specified that AFG usage successfully amends STZ-induced insulin conflict and liver grievance in T2DM. Systematically, AFG action diminished STZ-induced oxidative stress and inflammatory responses in the liver. In addition, we demonstrated that AFG also attenuates apoptosis and insulin secretion disorders in T2DM by adjusting the PI3K/AKT/GSK3ß signaling pathway. At the end, these discoveries recommend that AFG averts the development of T2DM through numerous types of machinery and proposes that AFG can also be used in order to treat T2DM in the future.

Traditional Chinese medicine Danggui Shaoyao San for the treatment of Alzheimer's disease: A Protocol for Systematic Review.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. Traditional Chinese formula Danggui Shaoyao San (DSS) has been considered a potential therapeutic approach for AD. However, no systemic review regarding its efficacy and safety has been conducted. Herein, we propose a protocol for the study that aims to evaluate the efficacy and safety of DSS in patients with AD. METHODS: Sixteen electronic databases including PubMed, EMBASE, Cochrane database, Web of science, Chinese National Knowledge Infrastructure, VIP, Wanfang database, China Biomedical Literature Database, Chinese Clinical Trial Registry System, Koreanstudies Information Service System, Oriental Medicine Advanced Searching Integrated System, Research Information Sharing Service, DBpia, Korean Traditional Knowledge Portal, Japanese CiNii databases and J-STAGE databases will be searched from the inception up to February 29, 2020. Randomized controlled trials (RCTs) that meet the pre-specified eligibility criteria will be included. RevMan software (V.5.3.5) will be used to perform data synthesis following data extraction and publication risk assessment. Subgroup and sensitivity analysis will be performed according to the condition of included RCTs. The primary outcomes include changes in the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), and Activities of Daily Living scale (ADL). Additional outcomes are clinical effective rate and adverse event rate. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of the evidence. RESULTS: This study will provide a well-reported and high-quality synthesis of RCTs on the efficacy and safety of DSS for the treatment of AD. CONCLUSION: This systematic review protocol will be helpful for providing evidence of whether DSS is an effective and safe therapeutic approach for patients with AD. ETHICS AND DISSEMINATION: Ethical approval is not necessary as this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020150450.

Meditation treatment of Alzheimer disease and mild cognitive impairment: A protocol for systematic review.

BACKGROUND: Growing body of scientific researches in recent years have suggested the promising effect of meditation on improving cognitive impairment of Alzheimer disease (AD) and mild cognitive impairment (MCI). This paper aims to provide a protocol for systematic review to evaluate the efficacy of meditation on cognition performance of patient with AD and MCI. METHODS: The Cochrane Library, PubMed, EMBASE, Web of Science, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database, and VIP information database will be searched systematically and electronically from establishment to March 2020. All published randomized controlled trials related will be included. Assessment of bias risk and data analyses will be implemented by Review Manager (V.5.3.5). The strength of the evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: A high-quality synthesis of current evidence of meditation for patient with AD and mild cognitive impairment will be provided in this study. CONCLUSION: This protocol of systematic review will be helpful for providing evidence of whether meditation is an effective and safe intervention for cognitive impairment of patient with AD and MCI. ETHICS AND DISSEMINATION: Ethical approval is unnecessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145932.

The roles of the TLR/NF­κB signaling pathway in the mutual interactions between the lung and the large intestine.

The 'exterior-interior relationship between the lung and the large intestine' is a classical basic theory in Traditional Chinese Medicine. The present study aimed to investigate the roles of the toll like receptor/nuclear factor­κB (TLR/NF­κB) signaling pathway in the mutual interactions between the lung and the large intestine. A rat model of allergic asthma complicated with intestinal flora disorder was established by oral administration of Candida albicans and intraperitoneal injection with ovalbumin. The number of inflammatory cells and expression levels immunoglobulin (Ig)E, secretory IgA, interleukin (IL)­4 and interferon­Î³ in serum and bronchoalveolar lavage fluid were subsequently measured. Bacterial colonies and expression of 16S ribosomal DNA were studied in feces samples and pathological alterations of lung tissues were identified. Furthermore, the expression levels of genes associated with the TLR/NF­κB signaling pathway in the lung and intestinal tissues were determined by reverse transcription­quantitative polymerase chain reaction. The results of the present study indicated that, in the rat model of allergic asthma complicated with intestinal flora disorder, the expression levels of IL­4 and IgE, and the numbers of inflammatory cells and C. albicans increased, and marked inflammatory cell infiltration was observed in lung tissues, suggesting that the animal model was successfully established. Furthermore, the present results revealed the mRNA expression levels of genes associated with the TLR/NF­κB signaling (including myeloid differentiation primary response 88, TNF receptor associated factor 6 and ß­arrestin) were upregulated in both of the lung and intestinal tissues of the model group rats. Collectively, the results demonstrated that the TLR/NF­κB signaling may serve roles in the mutual interactions between the lung and the large intestine, and TLR and NF­κB may be potential targets for the treatment of lung diseases complicated with intestinal disorders.