Supplementation of nicotinamide mononucleotide diminishes COX-2 associated inflammatory responses in macrophages by activating kynurenine/AhR signaling.

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for prostaglandin synthesis during inflammation and immune responses. Our previous results show that NAD+ level decreased in activated macrophages while nicotinamide mononucleotide (NMN) supplementation suppressed the inflammatory responses via restoring NAD+ level and downregulating COX-2. However, whether NMN downregulates COX-2 in mouse model of inflammation, and its underlying mechanism needs to be further explored. In the present study, we established LPS- and alum-induced inflammation model and demonstrated that NMN suppressed the inflammatory responses in vivo. Quantitative proteomics in mouse peritoneal macrophages identified that NMN activated AhR signaling pathway in activated macrophages. Furthermore, we revealed that NMN supplementation led to IDO1 activation and kynurenine accumulation, which caused AhR nuclear translocation and activation. On the other hand, AhR or IDO1 knockout abolished the effects of NMN on suppressing COX-2 expression and inflammatory responses in macrophages. In summary, our results demonstrated that NMN suppresses inflammatory responses by activating IDO-kynurenine-AhR pathway, and suggested that administration of NMN in early-stage immuno-activation may cause an adverse health effect.

Serum 25 hydroxyvitamin D in non-scarring alopecia: A systematic review and meta-analysis.

INTRODUCTION: Non-scarring alopecia mainly includes androgenetic alopecia (AGA), female pattern hair loss (FPHL), alopecia areata (AA), telogen effluvium (TE), anagen effluvium (AE) and so on. Many studies had investigated the serum 25-hydroxyvitamin D level and vitamin D deficiency of patients with these diseases, but opinions varied, and no conclusion was reached. METHODS: Relevant articles were retrieved through PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other databases. Serum 25-hydroxyvitamin D [25(OH) D] levels and vitamin D deficiency were used as our primary outcome. The odds ratio (OR) and the standardized mean difference (SMD) with 95% confidence interval were both examined for vitamin D deficiency and levels. RESULTS: Our meta-analysis had included a total of 3374 non-scarring alopecia patients and 7296 healthy controls from 23 studies through the inclusion criteria and exclusion criteria. We found non-scarring alopecia had decreased serum 25(OH)D level (WMD -7.29; 95% CI -9.21, -5.38) and increased vitamin D deficiency incidence (OR 3.11 95% CI 2.29, 4.22), compared with healthy controls. This meta-analysis chose to conduct random-effect model and subgroup analysis, because of the high heterogeneity (serum 25(OH)D level: I2 = 95%, vitamin D deficiency: I2 = 0%). CONCLUSION: Patients with non-scarring alopecia (including AA, FPHL, AGA and TE) have insufficient serum level of 25(OH)D and increased incidence of vitamin D deficiency. Vitamin D supplementation and monitoring for vitamin D deficiency may be helpful in treating non-scarring alopecia.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Biodegradable FePS3 nanoplatform for efficient treatment of osteosarcoma by combination of gene and NIR-II photothermal therapy.

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.

The complete mitochondrial genome of Camellia nitidissima (Theaceae).

The mitochondrial genome of Camellia nitidissima was sequenced by Illumina and Pacbio sequencing. The results of sequences showed that a total length was 949,915 bp, and the GC content was 45.7% in assembled mitochondrial genome of C. nitidissima. 71 unigenes had been found, including 36 coding proteins and 35 non-coding proteins. Subsequently, the phylogenetic tree was built on 24 plants with the maximum-likelihood method, which had high bootstrap value and fited to the angiosperm phylogeny group classification (APG IV). The study's findings unravel the taxonomic status of C. nitidissima and benefit the evolution study.

Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials.

Objective: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). Methods: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software. Results: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events. Conclusion: Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

Application of Acupuncture for Shoulder Pain Over the Past 22 Years: A Bibliometric Analysis.

Purpose: Acupuncture is widely used to relieve shoulder pain. A survey was conducted in order to recognize hotspots and frontiers of acupuncture for shoulder pain from the year 2000-2022. Methods: The Web of Science Core Collection was used to collect literature related to acupuncture therapy for shoulder pain, which spanned January 2000 to August 2022. The number of publications yearly, countries/institutions, journals, and keywords was analyzed and visualized in shoulder pain with acupuncture therapy by CiteSpace v.5.7.R5. Results: We totally analyzed 214 articles that met the inclusion criteria. The overall trend of publication volume continues to increase. The most productive authors in the field were César Fernández las Peñas and José L Arias-Buría, and the most influential author was Green S. Kyung Hee University and the People's Republic of China had the highest volume of publications, respectively. The most influential journal is Pain with high citation and impact factor. The hot keywords were "acupuncture", "shoulder pain", "dry needling", "randomized trial", and "injection". The research frontier in acupuncture for treating chronic shoulder pain was mainly "mechanism". Conclusion: Over the last 22 years, the findings of this bibliometric analysis have provided research trends and frontiers in clinical research on acupuncture therapy for patients with shoulder pain, which identifying hot topics and exploring new directions for the future may be helpful to researchers. Studying mechanisms underlying acupuncture therapy for shoulder pain remains a focus of future research.

Nicotinamide reprograms adipose cellular metabolism and increases mitochondrial biogenesis to ameliorate obesity.

Obesity poses a global health challenge and is a major risk factor for diabetes mellitus, cardiovascular diseases, hypertension, stroke and certain kinds of cancers. Although the effects of nicotinamide (NAM) on liver metabolism and diseases were well documented, its effects on adipose tissue are yet to be characterized. Herein, we found that NAM supplementation significantly reduced fat mass and improved glucose tolerance in obese mice. Proteomic analysis revealed that NAM supplementation upregulates mitochondrial proteins while quantitative polymerase chain reaction showed that PPARα and PGC1α were both upregulated in adipose tissues, proposing that NAM increased mitochondrial biogenesis in adipose tissue. Indeed, NAM treatment increased proteins related to mitochondrial functions including oxidative phosphorylation, fatty acid oxidation, and TCA cycle. Furthermore, isotope-tracing assisted metabolic profiling revealed that NAM activated NAMPT and increased cellular NAD+ level by 30%. Unexpectedly, we found that NAM also increased glucose derived amino acids to enhance glutathione synthesis for maintaining cellular redox homeostasis. Taken together, our results demonstrated that NAM reprogramed cellular metabolism, enhanced adipose mitochondrial functions to ameliorate symptoms associated with obesity.

Effects of Mindfulness-Based Therapy for Cancer Patients: A Systematic Review and Meta-analysis.

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD - 3.48, CI - 4.07, - 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD - 0.42, CI - 0.70, - 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD - 0.64, CI - 1.09, - 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages.

Chromosome-scale genome assembly and population genomics provide insights into the adaptation, domestication, and flavonoid metabolism of Chinese plum.

Globally, commercialized plum cultivars are mostly diploid Chinese plums (Prunus salicina Lindl.), also known as Japanese plums, and are one of the most abundant and variable fruit tree species. To advance Prunus genomic research, we present a chromosome-scale P. salicina genome assembly, constructed using an integrated strategy that combines Illumina, Oxford Nanopore, and high-throughput chromosome conformation capture (Hi-C) sequencing. The high-quality genome assembly consists of a 318.6-Mb sequence (contig N50 length of 2.3 Mb) with eight pseudo-chromosomes. The expansion of the P. salicina genome is led by recent segmental duplications and a long terminal repeat burst of approximately 0.2 Mya. This resulted in a significant expansion of gene families associated with flavonoid metabolism and plant resistance, which impacted fruit flavor and increased species adaptability. Population structure and domestication history suggest that Chinese plum may have originated from South China and provides a domestication route with accompanying genomic variations. Selection sweep and genetic diversity analysis enabled the identification of several critical genes associated with flowering time, stress tolerance, and flavonoid metabolism, demonstrating the essential roles of related pathways during domestication. Furthermore, we reconstructed and exploited flavonoid-anthocyanin metabolism using multi-omics analysis in Chinese plum and proposed a complete metabolic pathway. Collectively, our results will facilitate further candidate gene discovery for important agronomic traits in Chinese plum and provide insights into future functional genomic studies and DNA-informed breeding.

Consumer intention to purchase GM soybean oil in China: effects of information consistency and source credibility.

Consumers' potential reactions toward genetically modified (GM) foods affect their commercial feasibility and determine the decisions of economic agents. Inconsistent information on GM foods has created a sense of uncertainty in Chinese consumers' mind. This paper studies how the information about risks and benefits of GM foods from major sources influences Chinese consumer intention to purchase GM soybean oil. This analysis uses data from a survey of 880 residents randomly sampled from 13 cities in Jiangsu province. Using a multinomial logit model, we analyze the effects of information consistency and source credibility. The results show because of new information about 17.36% of consumers increase their intention to purchase GM soybean oil, and 15.10% of consumers decrease purchase intention. Compared to consistent information, inconsistent information can maximize change of purchase intention. The attitude change is greatest when there is a moderate difference between the new information and the initial consumer attitude. Furthermore, trust in biotechnology research institutes, government departments about GM, and GM experts are easier to promote consumers to change their intention to purchase GM soybean oil in a positive direction. Finally, we discuss implications for agencies as to strengthening the regulation and supervision of information sources, and including public-involved policies.Abbreviations: GM, Genetically modified; GMOs, Genetically modified organisms; AGGMO, Center of Agriculture's Genetically Modified Organisms' safety management and policy research organization at Nanjing Agricultural University; MARA, Ministry of Agriculture and Rural Affairs; ¥1 (RMB)≈$6.8 (USD).

Berberine mitigates cognitive decline in an Alzheimer's Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance.

Berberine is a natural isoquinoline alkaloid isolated from the Rhizoma coptidis. Recent advances in research throw more lights of its beneficial role towards Alzheimer's disease (AD), including promoting ß-amyloid (Aß) clearance, as well as inhibiting Aß production in the triple-transgenic mouse model of Alzheimer's disease (3×Tg AD). However, it remains unclarified if berberine has an effect on tau pathology. According to our study, berberine did not only significantly improve 3×Tg AD mice's spatial learning capacity and memory retentions, but also attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3ß and protein phosphatase 2A. Moreover, berberine reduced the level of tau through an autophagy-based route. It promoted autophagic clearance of tau by enhancing the activity of autophagy via the class III PI3K/beclin-1 pathway. Thus, our results suggest that berberine could mitigate cognitive decline by simultaneously targeting the hyperphosphorylation of tau and the autophagic clearance of tau in AD mice. These findings strongly support berberine as a potential drug candidate for AD.

The Synergistic Antitumor Effect of Tanshinone IIA Plus Adriamycin on Human Hepatocellular Carcinoma Xenograft in BALB/C Nude Mice and Their Influences on Cytochrome P450 CYP3A4 In Vivo.

OBJECTIVE: Hepatocellular carcinoma is one of the most common diseases that seriously threaten human life and health. In this study, we evaluated the inhibitory effect of tanshinone IIA (Tan IIA) combined with adriamycin (ADM) on human hepatocellular carcinoma and developed a platform to assess the function if Chinese herbal ingredients combined with chemotherapy drugs have synergistic antitumor effects in vivo. METHODS: Established animal model of human hepatocarcinoma HepG2 cell in nude mice. Mice were divided into model control group, Tan IIA group, ADM group, and Tan IIA + ADM group. The changes from general condition, weight, tumor volume, and inhibition rate were observed. The data were gathered from serum AST level and histopathological changes. The content and activity of cytochrome P450 were determined by spectrophotometric analysis. CYP3A4 protein expression was analyzed by western blotting. The binding model crystal structure of Tan IIA and ADM with pregnane X receptor (PXR) was evaluated by Discovery Studio 2.1. RESULTS: A combination of Tan IIA with ADM could improve life quality by relieving ADM toxicity, decreasing tumor volume, declining serum AST level, and improving liner pathological section in tumor-bearing mice. The inhibitory rates of Tan IIA, ADM, and cotreatment were 32.77%, 60.96%, and 73.18%, respectively. The Tan IIA group significantly enhanced the content of cytochrome b5, P450, and erythromycin-N-demethylase activity. CYP3A4 protein expression was enhanced obviously by the Tan IIA + ADM group. Virtual molecular docking showed that both Tan IIA and ADM could be stably docked with the same binding site of PXR but different interactions. CONCLUSIONS: Tan IIA in combination with ADM could improve the life quality in tumor-bearing mice and enhance the antitumor effect. The Tan IIA group increased the concentration of cytochrome P450 enzymes and activity. Combined Tan IIA with ADM could upregulate the CYP3A4 protein expression and make relevant interaction with protein PXR by virtual docking.

Magnetically targeted photothemal cancer therapy in vivo with bacterial magnetic nanoparticles.

The biomineralized bacterial magnetic nanoparticles (BMPs) have been widely studied for biomedical applications with their magnetic properties and a layer of biomembrane. Herein, BMPs were firstly used for magnetically targeted photothermal cancer therapy in vivo. A self-build C-shaped bipolar permanent magnet was used for magnetic targeting though the generation of a high gradient magnetic field within a small target area. For in vitro simulated experiment, BMPs had a high retention rate in magnetically targeted region with different flow rates. In H22 tumor bearing mice, the magnetic targeting induced a 40% increase of BMPs retention in tumor tissues. In vivo photothermal therapy with 808 nm laser irradiation could induce a complete tumor elimination with magnetic targeting. These results indicated that the systematically administrated BMPs with magnetic targeting would be promising for photothermal cancer therapy.

Sweet Olive Extract Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice.

Sweet olive (Osmanthus fragrans flowers) is used to treat dysentery and reduce phlegm and stasis in traditional Chinese medicine. Recently, we found that verbascoside, the major component in the sweet olive ethanolic extract (OFE), inhibited IL-8 secretion in human colorectal adenocarcinoma WiDr cells. However, evidence-based treatment of inflammatory bowel disease (IBD) with the extract is yet to be performed. To evaluate the therapeutic effect of OFE, we measured IL-8 suppression by OFE and verbascoside in a WiDr cell culture assay. In the IL-8 secretion assay, both OFE (100 µg/mL) and verbascoside (10 µM) significantly inhibited IL-8 production in WiDr cells. Furthermore, we designed cotreated (dextran sulfate sodium [DSS]+OFE-treated) and post-treated (DSS-OFE-treated) protocols to access the therapeutic effects of OFE in vivo. Mice treated with 500 mg/kg per day OFE exhibited significant improvement in IBD symptoms, including disease activity index score, body weight, and colon length maintenance. The suppressive effects on myeloperoxidase expression and lower histopathology scores (including neutrophil infiltration) for the colon were also found. These findings suggest that OFE exerts anti-inflammatory effect on DSS-induced colitis.

Maternal methyl donor supplementation during gestation counteracts bisphenol A-induced oxidative stress in sows and offspring.

OBJECTIVE: Maternal oxidative stress is harmful for embryonic, fetal, and placental development. The aim of this study was to investigate whether methyl donor supplementation during gestation effectively ameliorates maternal and placenta oxidative stress up to offspring. METHODS: Fifty-six Landrace × Yorkshire sows were randomly allocated to receive one of the following four diets during gestation: control diet (CON); control diet supplemented with methyl donor (MET); control diet supplemented with bisphenol A (BPA); and control diet supplemented with BPA and MET (BPA + MET). Blood sample, chorioallantois, and piglets' liver samples were analyzed for antioxidant status and mRNA expression of genes regarding oxidative status. RESULTS: MET diets lowered homocysteine concentration in the plasma of sows. They improved activity of antioxidant enzymes in chorioallantois and piglet plasma and liver (catalase, glutathione peroxidase, and total antioxidant capacity; P < 0.01), and also upregulated mRNA expression of copper, zinc-superoxide dismutase (P < 0.01), and glutathione peroxidase 1 (P < 0.05) in the chorioallantois and catalase (P < 0.01) in piglet liver compared with the control group. In contrast, BPA diets increased malondialdehyde (P < 0.01) levels in sows and piglets and decreased total antioxidant capacity (P < 0.01) concentration in sows and umbilical cord blood plasma, as well as downregulated copper, zinc-superoxide dismutase (P = 0.01) in piglet liver compared with MET group. CONCLUSION: BPA diets fed to sows during gestation aggravated oxidative stress status in sows and piglets, whereas the methyl donor diets enhanced antioxidant capacity of sows and piglets and ameliorated oxidative stress induced by BPA.

Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor ß-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women.

OBJECTIVE: Selected estrogen receptor ß-selective phytoestrogen (phytoSERM), a preparation of genistein, daidzein, and S-equol, has an 83-fold selective affinity for estrogen receptor (ER) ß, and may promote neuronal survival and estrogenic mechanisms in the brain without exerting feminizing activity in the periphery. The aim of this study was to assess the safety, tolerability, and single-dose pharmacokinetics of the phytoSERM formulation in perimenopausal and postmenopausal women. METHODS: Eighteen women aged 45 to 60 years from a 12-week clinical trial evaluating cognitive performance and vasomotor symptoms were randomly assigned to placebo, 50 mg, or 100 mg phytoSERM treatment groups. Plasma levels of the three parent phytoestrogens and their metabolites were measured before and at 2, 4, 6, 8, and 24 hours after ingestion by isotope dilution high-performance liquid chromatography (HPLC) electrospray ionization tandem mass spectrometry. RESULTS: Plasma concentrations of genistein, daidzein, and S-equol peaked at 9, 6, and 4 hours, respectively, for the 50-mg dose, and at 6, 6, and 5 hours, respectively, for the 100-mg dose. The maximum concentration (Cmax) and area under the curve (AUC) for the three parent compounds were greater in the 100-mg dose group, indicating a dose-dependent change in concentration with the phytoSERM treatment. No adverse events were elicited. CONCLUSIONS: A single-dose oral administration of the phytoSERM formulation was well-tolerated and did not elicit any adverse events. It was rapidly absorbed, reached high plasma concentrations, and showed a linear dose-concentration response in its pharmacokinetics. These findings are consistent with previously reported parameters for each parent compound (Clinicaltrials.gov NCT01723917).

Effects of 25-hydroxycholecalciferol supplementation in maternal diets on milk quality and serum bone status markers of sows and bone quality of piglets.

Twenty primiparous sows were allocated to two treatments to evaluate the effects of maternal 25-hydroxycholecalciferol (25OHD3 ) supplementation during gestation and lactation on milk quality and serum bone status markers of sows and bone quality of piglets. Immediately after mating, sows were randomly allotted to one of two diets supplemented with 50 µg/kg 25OHD3 or basal diets without 25OHD3 . Blood and milk samples were obtained. At birth and weaning, 10 piglets from each treatment were killed for bone quality analysis. 25OHD3 -fed sows provided one more piglet at farrowing and 1.17 more piglets at weaning than sows fed basal diets. The contents of solids not-fat, protein, fat or lactose were increased in milk from days 7 and 14 of lactation in 25OHD3 -supplemented sows and 25OHD3 concentrations in milk were increased by dietary 25OHD3 supplementation. Dietary 25OHD3 supplementation increased serum alkaline phosphatase activity but had no effect on serum tartrate-resistant acid phosphatase activity of sows. Maternal 25OHD3 supplementation improved bone strength, density and ash content of newborn piglets rather than those of weaning piglets. In conclusion, 25OHD3 supplementation in maternal diets improved reproductive performance, milk quality and bone status of sows as well as bone quality of newborn piglets.

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way.

BACKGROUND: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. METHODS: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins. RESULTS: Both tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin. CONCLUSIONS: Tanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.

Protective effect and potential mechanisms of Wei-Chang-An pill on high-dose 5-fluorouracil-induced intestinal mucositis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Wei-Chang-An pill (WCA pill), a traditional Chinese pharmaceutical preparation, possessed potential anti-inflammatory advantages and noteworthy gastrointestinal regulations in digestive diseases, which might represent a promising candidate for the treatment of intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). AIM OF THE STUDY: To analyze the bioactive constituents and investigate the effect of methanol extraction from WCA pill (WCA ext) on 5-FU induced IM with underlying mechanisms. MATERIALS AND METHODS: The analysis of serum bioactive constituents after WCA ext administration in rats was carried out by UHPLC-Quadrupole-Time of Flight-Mass Spectrometry. In mice, IM was induced by 5-FU and physical manifestations were measured during the period of drug delivery. Half of mice were assessed with histology, expression of inflammatory cytokines in ileum and plasma via hematoxylin and eosin staining, immunohistochemical staining as well as cytokine enzyme-linked immunosorbent assay test, respectively. Besides, gastric emptying (GE) and gastrointestinal transit (GIT) were further tested in the other half of 5-FU induced mice. RESULTS: Twenty-two compounds were identified or tentatively characterized. IM induced by 5-FU was improved significantly after treatment with WCA ext through reducing the body weight loss, relieving the severe diarrhea, and inhibiting the GE as well as GIT. Further assessments validated that WCA ext promoted the recovery of intestinal mucosa, evaluated the activity of enterocyte proliferation, maintained the integrity of tight junction, and ameliorated the inflammatory disturbances. CONCLUSIONS: These results suggested that WCA ext promoted the restoration of intestinal function in 5-FU-induced IM via regulating multiple sites of actions in intestinal homeostasis. Accordingly, WCA pill might be a promising therapeutic candidate for the prevention of IM during cancer chemotherapy.