Efficacy of the traditional Chinese medicine, Buyang Huanwu Decoction, at preventing taxane-induced peripheral neuropathy in breast cancer patients: A prospective, randomized, controlled study.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.

Traditional Chinese Medicine Shi-Bi-Man ameliorates psoriasis via inhibiting IL-23/Th17 axis and CXCL16-mediated endothelial activation.

BACKGROUND: Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera. PURPOSE: We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice. METHODS: We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin-eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells. RESULTS: SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction.

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.

Research on the anti-ageing mechanism of Prunella vulgaris L.

Prunella vulgaris L. (P. vulgaris) has long been considered to have antipyretic, analgesic and anti-inflammatory effects, lowering blood lipids and pressure. Many studies show that in addition to the traditional telomere attrition, DNA damage and epigenetic changes, immunosenescence is also a new possibility to explore the mechanism of ageing. Therefore, this herb may have potential anti-ageing effects. Typically, there are a series of markers that identify senescent cells, such as superoxide dismutase (SOD)2, an inhibitor of CDK4 (p16INK4A), tumor necrosis factor (TNF)-α, immune cells number, proliferation, and nuclear abnormalities. These changes rarely present in young tissues, while greatly increasing in response to ageing. Firstly, the ageing model of the Institute of Cancer Research (ICR) mouse was established by D-galactose subcutaneous injection. Then, SOD2, p16INK4A and TNF-α were detected by quantitative Real-time PCR (qPCR), Western Blot (WB) and Enzyme-Linked Immunosorbent Assay (ELISA). Simultaneously, senescent cells in livers were stained by hematoxylin and eosin (HE). The viability of splenocytes was detected by Cell Counting Kit-8(CCK-8). The difference in specific immune cells (NK cells, B lymphocytes and T lymphocytes) was detected by flow cytometry. Both low (100 mg/kg) and high (300 mg/kg) concentrations of P. vulgaris treated ageing ICR mice show anti-ageing alterations, such as p16INK4A decreased approximately 1/2 and SOD2 tripled in livers, TNF-α decreased from 1 to 0.6 in plasma, and T cells increased from 0.09 to 0.19%. Compared with the ageing group, the spleen cells in the Prunella-treated group had stronger proliferation ability. Thus, P. vulgaris could have an anti-ageing effect. This is the first study to demonstrate the anti-ageing effect of P. vulgaris. It may also be capable of preventing a variety of age-related diseases.

Effect of gut microbiome regulated Taohong Siwu Decoction metabolism on glioma cell phenotype.

Introduction: To establish a new model for exploring the mechanism of the gut microbiome and drug metabolism, we explored whether Taohong Siwu Decoction acts after metabolism by intestinal flora under the premise of clarifying the interaction between intestinal flora and drug metabolism. Methods: Taohong Siwu Decoction (TSD) was fed to germ-free mice and conventional mice, respectively. The serum from both groups of mice was removed and co-cultured with glioma cells in vitro. The co-cultured glioma cells were compared separately for changes at the RNA level using RNA-seq technology. The genes of interest in the comparison results were selected for validation. Results: The differences in the phenotypic alterations of glioma cells between serum from TSD-fed germ-free mice and normal mice were statistically significant. In vitro experiments showed that Taohong Siwu Decoction-fed normal mouse serum-stimulated glioma cells, which inhibited proliferation and increased autophagy. RNA-seq analysis showed that TSD-fed normal mouse serum could regulate CDC6 pathway activity in glioma cells. The therapeutic effect of TSD is significantly influenced by intestinal flora. Conclusion: The treatment of tumors by TSD may be modulated by intestinal flora. We established a new method to quantify the relationship between intestinal flora and the regulation of TSD efficacy through this study.

Paeonol ameliorates endometrial hyperplasia in mice via inhibiting PI3K/AKT pathway-related ferroptosis.

BACKGROUND: Paeonol (Pae) is one of the active ingredients from components of Guizhi Fuling Capsule, a traditional Chinese medicine widely used for the treatment of women's diseases, which exhibits various biological and pharmacological activities. PURPOSE: The objective of this study was to investigate the molecular mechanism underlying the role of Pae in protecting against endometrial hyperplasia (EH). METHODS: CCK-8 assay was performed to detect the effect of Pae on cell proliferation. Hematoxylin and eosin (H&E) staining was performed to evaluate uterine tissue structure. A network pharmacology study was performed to search the disease targets. Single-cell transcriptome analysis was performed with uterine tissues from 3 healthy donors and 3 EH patients on 10X Genomics platform. Changes in lipid peroxidation were detected by the MDA reaction. IHC assay, Western blot, immunofluorescence and RT-qPCR were used to study the effects of estradiol and Pae on the expression levels of GPX4, PI3K, AKT, p-PI3K, p-AKT in mice. RESULTS: Pae treatment resulted in a decrease in cell viability of endometrial epithelial cells. Loss of uterus weight and morphology changes were observed in mice. In addition, Fe iron concentration and MDA levels increased, while the expression of GPX4, p-PI3K and p-AKT diminished. CONCLUSIONS: Pae exhibited obvious alleviative activity in estradiol-induced mice via PI3K/AKT signaling pathway-regulated ferroptosis.

Single-cell transcriptomics reveals the natural product Shi-Bi-Man promotes hair regeneration by activating the FGF pathway in dermal papilla cells.

BACKGROUND: Finasteride and minoxidil are two commonly used drugs for the treatment of hair loss. However, these two drugs have certain side effects. Thus, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. Shi-Bi-Man (SBM) is a hair health supplement that darkens hair and contains ginseng radix, tea polyphenols, polygonum multiflorum, radix angelicae sinensis, aloe, linseed, and green tea extract. PURPOSE: This study aimed to find potential effective monomer components to promote hair regeneration from SBM and to explore the mechanism of SBM to promote hair regeneration. METHODS: Supplementation with the intragastric administration or smear administration of SBM in artificially shaved C57BL/6 mice, observe its hair growth. UPLC/MS and UPLC/LTQ-Orbitrap-MS detect the main components in SBM and the main monomers contained in the skin after smearing, respectively. A network pharmacology study on the main components of SBM and single-cell RNA sequencing was performed to explore the role of SBM for hair regeneration. RESULTS: SBM significantly induced hair growth compared with a control treatment. TSG and EGCG were the main monomers in the skin after SBM smearing. The results of single-cell sequencing revealed that after SBM treatment, the number of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) increased significantly. Cell interactions and volcano dots show that the interaction of the FGF signaling pathway was significantly enhanced, in which Fgf7 expression was especially upregulated in DPCs. In addition, the Wnt signaling pathway also had a partially enhanced effect on the interactions between various cells in the skin. The network pharmacology study showed that the promotion of the FGF and Wnt pathways by SBM was also enriched in alopecia diseases. CONCLUSION: We report that SBM has a potential effect on the promotion of hair growth by mainly activating the FGF signaling pathway. The use of SBM may be a novel therapeutic option for hair loss.

Responses of the root morphology and photosynthetic pigments of ryegrass to fertilizer application under combined petroleum-heavy metal stress.

With developments in industry, petroleum and heavy metal pollution are increasingly affecting soil, significantly harming the environment, biosecurity, and human health. Therefore, the remediation of contaminated soil is becoming increasingly important. In this study, ryegrass (Lolium perenne L.) was planted in petroleum-heavy metal co-contaminated soil with the application of nitrogen and phosphorus fertilizers. Three treatments were set up: uncontaminated soil + ryegrass (SH); petroleum-heavy metal co-contaminated soil + ryegrass (SPGH); and petroleum-heavy metal co-contaminated soil + ryegrass + nitrogen and phosphorus fertilizer (SPGH + NP). The results showed that the petroleum-heavy metal co-contamination promoted increases in the root length, surface area, volume, and diameter of ryegrass roots, increasing the below-ground biomass and decreasing the photosynthetic pigment content in the early stages of the experiment. The ratios of chlorophyll a/b and chlorophyll/carotenoid also increased. However, the application of fertilizer reduced the length, surface area, volume, and diameter of ryegrass roots in the co-contaminated soil, and the below-ground biomass decreased while the above-ground biomass increased. Furthermore, the photosynthetic pigment content was significantly higher than that in the unfertilized treatment and the chlorophyll a/b ratio decreased while the chlorophyll/carotenoid ratio increased. Therefore, fertilizers could alleviate the toxic effects of petroleum-heavy metal combined pollution on ryegrass roots and promote the synthesis of chlorophyll and other pigments, thus reducing the inhibitory effect of petroleum-heavy metal combined pollution on ryegrass growth and facilitating the remediation of the polluted soil.

A search of only four key databases would identify most randomized controlled trials of acupuncture: A meta-epidemiological study.

Little research has been conducted to assess which specific databases should be searched when performing a systematic review (SR) on acupuncture. The current study aimed to identify key databases and the optimal database combination to retrieve randomized controlled trials (RCTs) on acupuncture for inclusion in SRs. A systematic search for SRs in the field of acupuncture was conducted in order to identify target databases and RCTs were extracted from the SRs that had searched all target databases. The proportions of SRs that had achieved 100%, 95%, or 90% recall of RCTs and the total recall of RCTs in various combinations of target databases were calculated. Sensitivity analysis was performed on those SRs that included 10 or more RCTs. CNKI, WanFang, VIP, PubMed, CENTRAL and Embase were regarded as target databases. A total of 4349 acupuncture RCTs were extracted from 286 SRs. Searching all six target databases retrieved 99.3% of all RCTs while 99.1% were recalled by searching the combination of CNKI, WanFang, PubMed and CENTRAL. There were no significant differences on total recall of RCTs (p = 0.549) or in the proportion of SRs with 90% recall of RCTs (97.2% vs. 97.6%; p = 0.794) between searching the above four and the full six target databases. Most results were similar in the sensitivity analysis. The combined retrieval power of CNKI, WanFang, PubMed and CENTRAL was considered an efficient choice to retrieve acupuncture RCTs included in SRs.

Variation of microbial activities and communities in petroleum-contaminated soils induced by the addition of organic materials and bacterivorous nematodes.

Bacterivorous nematodes are abundant in petroleum-contaminated soils. However, the ecological functions of bacterivorous nematodes and their impacts together with the addition of organic materials on the activity and diversity of microorganisms in petroleum-contaminated soils remain unknown. To assess such effects, six treatments were established in this study, including uncontaminated nematodes-free soil (Control), petroleum-contaminated soil (PC), petroleum-contaminated soil + 5 nematodes per gram dry soil (PCN), and petroleum-contaminated soil + 5 nematodes per gram dry soil + 1% wheat straw (PCNW), or + 1% rapeseed cake (PCNR), or + 1% biochar (PCNB). Results showed that the enzyme activities in the six treatments generally increased firstly and then decreased during the incubation period. Compared with Control, the invertase activity in PCNW, PCNR, and PCNB increased by 80.6%, 313.5%, and 12.4%, respectively, whereas the urease activity in PC, PCN, PCNW, PCNR, and PCNW increased by 1.2%, 25.5%, 124.3%, 105.3%, and 25.5%, respectively. Petroleum pollution, inoculation of bacterivorous nematodes, and the addition of organic materials all significantly boosted the concentrations of phospholipid fatty acids (PLFAs) of soil bacteria, actinobacteria, and total microorganisms, and increased the concentrations of both G+ and G- bacteria PLFAs and the ratio of G-/G+. The concentration of fungi PLFAs and the ratio of fungi to bacteria were significantly higher in PCNW and PCNR than those in other treatments. Overall, adding bacterivorous nematodes and organic materials to the petroleum-contaminated soil significantly improved soil microbial activity and community structure, suggesting that bacterivorous nematodes could be used for the bioremediation in petroleum contaminated soils.

Effect of indole-3-acetic acid supplementation on the physiology of Lolium perenne L. and microbial activity in cadmium-contaminated soil.

Cadmium (Cd) pollution has led to a serious deterioration in soil quality, plant growth, and human health. Therefore, restoration of soil quality is imperative. Phytoremediation is inexpensive and yields acceptable outcomes. Phytoremediation involves interaction between plant physiology and microbial activity and has been widely used in the remediation of Cd-contaminated soil. In the present study, Lolium perenne L. (perennial ryegrass) was planted in Cd-spiked soil and indole-3-acetic acid (IAA) was used to explore the physiological and biochemical characteristics of ryegrass as well as soil enzyme activity to remove Cd. The present study provides a theoretical basis for the phytoremediation of Cd-contaminated soil. The study investigated the effect of 30-mg/kg Cd-spiked soil on ryegrass (C) and 30-mg/kg Cd-spiked soil on ryegrass treated with 10-mg/kg IAA (CI) compared with uncontaminated soil and ryegrass as the control. At the end of the experiment, the ryegrass biomass, total chlorophyll, superoxide dismutase (SOD) activity, and soil invertase activity in C group were decreased by 33.7%, 23.0%, 29.7%, and 18.3%, respectively, whereas the peroxidase (POD) activity and soil basal respiration increased by 17.1% and 87.9%, respectively, compared with the control. In the CI group, the biomass of ryegrass, chlorophyll content, SOD activity, sucrase activity, fluorescein diacetate (FDA) hydrolase activity, and Cd removal rates increased by 14.5%, 19.9%, 24.3%, 12.1%, 20.4%, and 15.1%, respectively, whereas the POD activity, soil basal respiration, and Cd residues in the soil declined by 8.0%, 15.0%, and 17.0%, respectively, compared with the C group. Therefore, exposure to exogenous IAA alleviated the Cd stress on ryegrass and soil microorganisms and improved Cd absorption by ryegrass from the contaminated soil.

Chest X-Ray Diagnostic Quality Assessment: How Much Is Pixel-Wise Supervision Needed?

Chest X-ray is an important imaging method for the diagnosis of chest diseases. Chest radiograph diagnostic quality assessment is vital for the diagnosis of the disease because unqualified radiographs have negative impacts on doctors' diagnosis and thus increase the burden on patients due to the re-acquirement of the radiographs. So far no algorithms and public data sets have been developed for chest radiograph diagnostic quality assessment. Towards effective chest X-ray diagnostic quality assessment, we analyze the image characteristics of four main chest radiograph diagnostic quality issues, i.e. Scapula Overlapping Lung, Artifact, Lung Field Loss, and Clavicle Unflatness. Our experiments show that general image classification methods are not competent for the task because the detailed information used for quality assessment by radiologists cannot be fully exploited by deep CNNs and image-level annotations. Then we propose to leverage a multi-label semantic segmentation framework to find the problematic regions, and then classify the quality issues based on the results of segmentation. However, subsequent classification is often negatively affected by certain small segmentation errors. Therefore, we propose to estimate a distance map that measures the distance from a pixel to its nearest segment, and use it to force the prediction of semantic segmentation more holistic and suitable for classification. Extensive experiments validate the effectiveness of our semantic-segmentation-based solution for chest X-ray diagnostic quality assessment. However, general segmentation-based algorithms requires fine pixel-wise annotations in the era of deep learning. In order to reduce reliance on fine annotations and further validate how important pixel-wise annotations are, weak supervision for segmentation is applied, and demonstrates its ability close to that of full supervision. Finally, we present ChestX-rayQuality, a chest radiograph data set, which comprises 480 frontal-view chest radiographs with semantic segmentation annotations and four labels of quality issue. Also, other 1212 chest radiographs with limited annotations are imported to validate our algorithms and arguments on larger data set. These two data set will be made publicly available.

Fat-1 expression alleviates atherosclerosis in transgenic rabbits.

Atherosclerosis is the main cause of cardiovascular diseases. The Fat-1 gene can express the n-3 fatty acid desaturase, which converts n-6 polyunsaturated fatty acids (PUFA) to n-3 PUFAs. The role of n-3 PUFAs in atherosclerosis is widely debated. This study explored the effect of n-3 PUFAs on atherosclerosis in rabbits. In this study, atherosclerosis was induced in Fat-1 transgenic rabbits and their littermate (WT) rabbits by feeding a high-cholesterol diet containing 0.3% cholesterol and 3% soybean oil for 16 weeks. Plasma lipid, fatty acid and pathological analyses of atherosclerotic lesions were conducted. Fatty acid composition in the liver and muscle showed that n-3 PUFAs increased and n-6 PUFAs decreased in the Fat-1 group. Plasma high-density lipoprotein cholesterol (HDL-C) levels were significantly increased in the Fat-1 group, and the atherosclerotic lesion area of the aortic arch in Fat-1 transgenic rabbits was significantly reduced. Histological analysis showed that smooth muscle cells (SMCs) in atherosclerotic lesions decreased significantly. In conclusion, n-3 PUFAs improve atherosclerosis in Fat-1 transgenic rabbits, and this process may depend on the increase in plasma HDL-C and the decrease in the amount of SMCs in atherosclerotic plaques.

Network Pharmacology-Based Analysis of Gegenqinlian Decoction Regulating Intestinal Microbial Activity for the Treatment of Diarrhea.

Gegenqinlian decoction (GD) has been extensively used for the treatment of diarrhea with intestinal dampness-heat syndrome (IDHS) with a satisfying therapeutic effect. The purpose of this study is to clarify the active ingredients and mechanism of GD in the treatment of diarrhea with IDHS. The TCMSP database was used to screen out the active ingredients of the four Chinese herbal medicines in GD, and the targets of the active ingredients were predicted. We selected the targets related to diarrhea through the DisGeNET database, then used the NCBI database to screen out related targets of lactase and sucrase, and constructed the visual network to search for the active ingredients of GD in the treatment of diarrhea and related mechanisms of the targets. Combined with network pharmacology, we screened out 146 active ingredients in GD corresponding to 252 ingredient targets, combined with 328 disease targets in diarrhea, and obtained 12 lactase targets and 11 sucrase targets. The key active ingredients involved quercetin, formononetin, ß-sitosterol kaempferol, and wogonin. Furthermore, molecular docking showed that these five potential active ingredients had good affinities with the core targets PTGS2. The active ingredients in GD (such as quercetin, formononetin, and ß-sitosterol) may increase the microbial activity of the intestinal mucosa of mice and reduce the microbial activity of the intestinal contents through multiple targets, thereby achieving the effect of treating diarrhea.

Guan Xin Dan Shen formulation protects db/db mice against diabetic cardiomyopathy via activation of Nrf2 signaling.

Guan Xin Dan Shen formulation (GXDSF) is a widely used treatment for the management of coronary heart disease in China and is composed of three primary components: Dalbergiae odoriferae Lignum, Salviae miltiorrhizae Radix et Rhizoma and Panax notoginseng Radix et Rhizoma. However, the potential use of GXDSF for the management of diabetic cardiomyopathy (DCM) has not been previously assessed. The present study aimed to assess the effects of GXDSF on DCM, as well as the underlying mechanism. In the present study, db/db mice were used. Following treatment with GXDSF for 10 weeks, fasting blood glucose, insulin sensitivity, serum lipid levels and cardiac enzyme levels were detected. Cardiac pathological alterations and cardiac function were assessed by performing hematoxylin and eosin staining and echocardiograms, respectively. TUNEL assays were conducted to assess cardiomyocyte apoptosis. Additionally, reverse transcription­quantitative PCR and western blotting were performed to evaluate the expression of apoptosis­associated genes and proteins, respectively. In the model group, the db/db mice displayed obesity, hyperlipidemia and hyperglycemia, accompanied by noticeable myocardial hypertrophy and diastolic dysfunction. Following treatment with GXDSF for 10 weeks, serum triglyceride levels were lower and insulin sensitivity was enhanced in db/db mice compared with the model group, which indicated improvement in condition. Cardiac hypertrophy and dysfunction were also improved in db/db mice following treatment with GXDSF, resulting in significantly increased left ventricular ejection fraction and fractional shortening compared with the model group. Following treatment with metformin or GXDSF, model­induced increases in levels of myocardial enzymes were decreased in the moderate and high dose groups. Moreover, the results indicated that, compared with the model group, GXDSF significantly inhibited cardiomyocyte apoptosis in diabetic heart tissues by increasing Bcl­2 expression and decreasing the expression levels of Bax, cleaved caspase­3 and cleaved caspase­9. Mechanistically, GXDSF enhanced Akt phosphorylation, which upregulated antioxidant enzymes mediated by nuclear factor erythroid 2­related factor 2 (Nrf2) signaling. Collectively, the results of the present study indicated that GXDSF attenuated cardiac dysfunction and inhibited cardiomyocyte apoptosis in diabetic mice via activation of Akt/Nrf2 signaling. Therefore, GXDSF may serve as a potential therapeutic agent for the management of DCM.

[Effect of Guanxin Danshen Formulation on diabetic kidney disease in db/db mice through regulation of Nrf2 pathway].

Diabetic kidney disease(DKD) has become a primary cause of end-stage kidney disease, without any effective treatment available. In this study, we assessed the protective effect of Guanxin Danshen Formulation(GXDSF) on diabetic nephropathy in db/db mice. The db/m and db/db mice were randomly divided into 4 groups: control group, model group, metformin group, and GXDSF group. After 8 weeks' treatment with GXDSF, metformin or normal saline, the mice were sacrificed, and the blood and kidney tissues were collected for the further analysis. Compared with the model group, TG, TCH and LDL levels significantly decreased in the GXDSF group. The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume, basement-membrane thickening and mesangial cell proliferation, which could be significantly alleviated by GXDSF treatment. GXDSF treatment also reduced serum creatinine and BUN. Meanwhile, GXDSF treatment markedly elevated GSH-PX levels, while reduced LDH and MDA levels in the kidney tissues. Western blot assay showed that GXDSF evidently up-regulated protein levels of ERα and p-Akt, and subsequently promoted HO-1 expression mediated by Nrf2. These data collectively indicated that GXDSF protects db/db mice against DN by regulating ERα and Nrf2-mediated HO-1 expression.

Role of tryptophan-metabolizing microbiota in mice diarrhea caused by Folium sennae extracts.

BACKGROUND: Although reports have provided evidence that diarrhea caused by Folium sennae can result in intestinal microbiota diversity disorder, the intestinal bacterial characteristic and specific mechanism are still unknown. The objective of our study was to investigate the mechanism of diarrhea caused by Folium sennae, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality. RESULTS: For the intervention of Folium sennae extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by Folium sennae extracts were distinctly separated from control group. Combining PPI network analysis, cytochrome P450 enzymes metabolism was the main signaling pathway of diarrhea caused by Folium sennae. Moreover, 10 bacterial flora communities had statistical significant difference with Folium sennae intervention: the abundance of Paraprevotella, Streptococcus, Epulopiscium, Sutterella and Mycoplasma increased significantly; and the abundance of Adlercreutzia, Lactobacillus, Dehalobacterium, Dorea and Oscillospira reduced significantly. Seven of the 10 intestinal microbiota communities were related to the synthesis of tryptophan derivatives, which affected the transformation of aminotryptophan into L-tryptophan, leading to abnormal tryptophan metabolism in the host. CONCLUSIONS: Folium sennae targeted cytochrome P450 3A4 to alter intestinal bacterial characteristic and intervene the tryptophan metabolism of intestinal microbiota, such as Streptococcus, Sutterella and Dorea, which could be the intestinal microecological mechanism of diarrhea caused by Folium sennae extracts.

Rod-based urchin-like hollow microspheres of Bi2S3: Facile synthesis, photo-controlled drug release for photoacoustic imaging and chemo-photothermal therapy of tumor ablation.

Hollow nanostructures have been evoked considerable attention owing to their intriguing hollow interior for important and potential applications in drug delivery, lithium battery, catalysis and etc. Herein, Bi2S3 hollow microspheres with rod-based urchin-like nanostructures (denoted as U-BSHM) were synthesized through a facile and rapid ion exchanging method using a particular hard template. The growth mechanism of the U-BSHM has been investigated and illustrated by the morphological evolution of the different samples at early stages. The obtained U-BSHM exhibited strong and wide UV-vis-NIR absorption ability and outstanding photothermal conversion efficiency. Thus, the U-BSHM can be used as spatio-temporal precisely controlled carrier by loading the mixture of 1-tetradecanol (phase change material, PCM) with melting point around 38 °C and hydrophilic chemotherapeutic doxorubicin hydrochloride (denoted as DOX) into the hollow interior to form (PCM + DOX)@Bi2S3 nanocomposites (denoted as PD@BS) for photoacoustic (PA) imaging and chemo-photothermal therapy of the tumors. When exposed to 808 nm near infrared light (NIR) laser irradiation, this nanocomposites could elevate the temperature of the surroundings by absorption and conversion of the NIR photons into heat energy, which inducing the triggered release of DOX from the hollow interior once the temperature reach up to the melting point of PCM. The killing efficiency of the chemo-photothermal therapy was systematically validated both in vitro and in vivo. In the meanwhile, the implanted tumor was completely restrained through PA imaging and combined therapies. Therefore, this kind of urchin-like hollow nanostructures would be used as important candidates for the multimodal bioimaging and therapy of tumors.

Effect of Panax notoginseng Saponins and Major Anti-Obesity Components on Weight Loss.

The prevalence of individuals who are overweight or obese is rising rapidly globally. Currently, majority of drugs used to treat obesity are ineffective or are accompanied by obvious side effects; hence, the options are very limited. Therefore, it is necessary to find more effective and safer anti-obesity drugs. It has been proven in vivo and in vitro that the active ingredient notoginsenosides isolated from traditional Chinese medicine Panax notoginseng (Burk.) F. H. Chen exhibits anti-obesity effects. Notoginsenosides can treat obesity by reducing lipid synthesis, inhibiting adipogenesis, promoting white adipose tissue browning, increasing energy consumption, and improving insulin sensitivity. Although notoginsenosides are potential drugs for the treatment of obesity, their effects and mechanisms have not been analyzed in depth. In this review, the anti-obesity potential and mechanism of action of notoginsenosides were analyzed; thus laying emphasis on the timely prevention and treatment of obesity.

Herb-Induced Liver Injury: Phylogenetic Relationship, Structure-Toxicity Relationship, and Herb-Ingredient Network Analysis.

Currently, hundreds of herbal products with potential hepatotoxicity were available in the literature. A comprehensive summary and analysis focused on these potential hepatotoxic herbal products may assist in understanding herb-induced liver injury (HILI). In this work, we collected 335 hepatotoxic medicinal plants, 296 hepatotoxic ingredients, and 584 hepatoprotective ingredients through a systematic literature retrieval. Then we analyzed these data from the perspectives of phylogenetic relationship and structure-toxicity relationship. Phylogenetic analysis indicated that hepatotoxic medicinal plants tended to have a closer taxonomic relationship. By investigating the structures of the hepatotoxic ingredients, we found that alkaloids and terpenoids were the two major groups of hepatotoxicity. We also identified eight major skeletons of hepatotoxicity and reviewed their hepatotoxic mechanisms. Additionally, 15 structural alerts (SAs) for hepatotoxicity were identified based on SARpy software. These SAs will help to estimate the hepatotoxic risk of ingredients from herbs. Finally, a herb-ingredient network was constructed by integrating multiple datasets, which will assist to identify the hepatotoxic ingredients of herb/herb-formula quickly. In summary, a systemic analysis focused on HILI was conducted which will not only assist to identify the toxic molecular basis of hepatotoxic herbs but also contribute to decipher the mechanisms of HILI.