Morusin inhibits breast cancer-induced osteolysis by decreasing phosphatidylinositol 3-kinase (PI3K)-mTOR signalling.

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.

[Molecular identification of animal species of Bufonis Venenum from secretions].

The animal species is one of the key factors affecting the quality of Bufonis Venenum. The quality of Bufonis Venenum derived from Bufo bufo gargarizans is significantly higher than that from B. melanostictus. Since Bufonis Venenum is from secretions, the conventional identification methods are difficult to identify the animal species due to the lack of the appearance and morphology of the animals. The rapid development of molecular identification technology has provided new methods for the identification of Bufonis Venenum. However, because of the low content and serve degradation of residual DNA in secretions, the research on the molecular identification of Chinese medicinal materials from secretions remains to be carried out. To understand the animal species of Bufonis Venenum, this study collected 83 samples of Bufonis Venenum, including 7 commercially available samples, 5 reference medicinal materials, and 71 animal samples from which Bufonis Venenum was prepared according to the method in the 2020 edition of the Chinese Pharmacopoeia. Different DNA extraction methods were used and compared, and the mitochondrial 16S rRNA gene fragments were amplified, on the basis of which the phylogenetic trees were built. Finally, molecular identification of the animal species of the samples was performed. The results showed that the DNA extracted from Bufonis Venenum by the reagent kit had good quality, and 16S rRNA sequences were successfully amplified from 80 out of the 83 samples. In addition, 71 16S rRNA sequences of the animal species of Bufonis Venenum were downloaded from GenBank. The phylogenetic trees constructed based on the neighbor-joining(NJ) method and the Bayesian inference(BI) method showed that the samples derived from B. bufo gargarizans and B. melanostictus were clustered into separate monophyletic clades, with the support of 100%(NJ) and 1.00(BI), respectively. The animal species of both commercially available samples and reference medicinal materials were B. bufo gargarizans. In conclusion, DNA can be extracted from Bufonis Venenum derived from secretions, and the 16S rRNA gene sequences can be amplified, which can be used for molecular identification of the animal species of Bufonis Venenum. The findings provide a reference for the quality control of Bufonis Venenum and the identification of animal species of medicinal materials derived from secretions.

Tibetan tea consumption prevents obesity by modulating the cellular composition and metabolic reprogramming of white adipose tissue.

Obesity, a global health concern, is linked with numerous metabolic and inflammatory disorders. Tibetan tea, a traditional Chinese beverage rich in theabrownin, is investigated in this study for its potential anti-obesity effects. Our work demonstrates that Tibetan tea consumption in C57BL/6J mice significantly mitigates obesity-related phenotypic changes without altering energy intake. Computational prediction revealed that Tibetan tea consumption reconstructs gene expression in white adipose tissue (WAT), promoting lipid catabolism and thereby increasing energy expenditure. We also note that Tibetan tea suppresses inflammation in WAT, reducing adipocyte hyperplasia and immune cell infiltration. Furthermore, Tibetan tea induces profound metabolic reprogramming, influencing amino acid metabolic pathways, specifically enhancing glutamine synthesis, which in turn suppresses pro-inflammatory chemokine production. These findings highlight Tibetan tea as a potential candidate in obesity prevention, providing a nuanced understanding of its capacity to modulate the cellular composition and metabolic landscape of WAT.

Cationic fructan-based pH and intestinal flora dual stimulation nanoparticle with berberine for targeted therapy of IBD.

Inflammatory bowel disease (IBD) can cause intestinal microbial imbalance and aggravate intestinal inflammation. Mixed fructan is more easily fermented by colonic microorganisms and can be used as colonic drug delivery materials. Here, we constructed a mixed fructan based nanoparticle with dual targeted stimulation of pH and intestinal flora to effectively deliver berberine for the treatment of ulcerative colitis (UC). The complex of fructan based nanoparticle and berberine (BBRNPs) significantly ameliorated the inflammatory response of sodium dextran sulfate (DSS)-induced colitis in mice by inhibiting the activation of NF-κB/STAT-3 pathway and increasing tight junction protein expression in vivo. Importantly, BBRNPs improved the responsiveness of colitis microbiome and effectively regulated the relative homeostasis of harmful flora Enterobacteriaceae and Escherichia-shigolla, and beneficial flora Ruminococcaceae and Akkermansiaceae. This study provides a promising strategy for the effective treatment of UC and expands the application of branched fructan in pharmaceutics.

[Effect of Xiaoxuming Decoction on activation of astrocytes in acute cerebral ischemia/reperfusion injury].

This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury. The model of cerebral IR injury was established using the middle cerebral artery occlusion method. Fluorocitrate(FC), an inhibitor of astrocyte activation, was applied to inhibit astrocyte activation. Rats were randomly divided into a sham group, a model group, a XXMD group, a XXMD+FC group, and a XXMD+Vehicle group. Neurobehavioral changes at 24 hours after cerebral IR injury, cerebral infarction, histopathological changes observed through HE staining, submicroscopic structure of astrocytes observed through transmission electron microscopy, fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence, and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group. The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group. The XXMD group, the XXMD+FC group, and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats. The pathological changes in the brain were evident in the model group, while the XXMD group, the XXMD+FC group, and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats. The submicroscopic structure of astrocytes in the model group showed significant swelling, whereas the XXMD group, the XXMD+FC group, and XXMD+Vehicle group protected the submicroscopic structure of astrocytes. The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group. However, the XXMD group, the XXMD+FC group, and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1. The combination of XXMD and FC showed a more pronounced effect. These results indicate that XXMD can improve cerebral IR injury, possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.

Characteristics, differential diagnosis, individualized treatment, and prevention of hyperhomocysteinemia in newborns.

OBJECTIVES: This study aimed to investigate the incidence rate, clinical phenotype, gene variation spectrum, and prognosis of neonatal hyperhomocysteinemia (HHcy) and explore its diagnosis, individualised treatment, and prevention strategies. METHODS: We screened 84722 neonates for HHcy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with biochemical detection, urine gas chromatography-mass spectrometry (GC-MS), and next-generation sequencing (NGS) for gene analysis to comprehensively differentiate and diagnose diseases. RESULTS: 18 children (P1-P18) were diagnosed with methylmalonic acidemia (MMA) and HHcy, and fourteen known and one new variant of the MMACHC gene were found. Five children showed poor mental reactions, brain dysplasia, lethargy, hyperbilirubinemia, and jaundice, whereas the other 13 children had no evident abnormalities. These children were all cobalamin- and folic acid-reactive types, and they were mainly supplemented with cobalamin, L-carnitine, betaine, and folic acid. The mother of P12 had a prenatal diagnosis at the next pregnancy; the results showed that MMACHC gene was not pathogenic and she gave birth to a healthy baby. One child (P19) was diagnosed with methylenetetrahydrofolate reductase (MTHFR) deficiency, and one new mutation was detected in the MTHFR gene. Patient P19 showed congenital brain dysplasia, neonatal anaemia, and hyperbilirubinemia, and treatment consisted mainly of betaine and cobalamin supplementation. One child (P20) was confirmed to have methionine adenosyltransferase I (MAT I) deficiency but had no clinical manifestations. After treatment, all the children had a good prognosis. CONCLUSION: The incidence of neonatal HHcy in the Zibo area was 1/4236, and the common pathogenic variants were c.609G>A, c.80A>G, and c.482G>A in the MMACHC gene. Patients with HHcy can achieve a good prognosis if pathogenic factors and targeted treatment are identified. Gene analysis and prenatal diagnosis contribute to the early prevention of HHcy.

Effects of Tai chi in knee osteoarthritis patients: An overview of systematic reviews and meta-analyses.

OBJECTIVE: Tai Chi (TC) is a complementary therapy for knee osteoarthritis (KOA). Although systematic reviews (SRs) and meta-analyses (Mas) of efficacy studies have been published, the results remain uncertain, and their quality has not yet been fully evaluated. Here, we summarize the existing SRs/Mas, evaluate their quality and level of evidence, and provide a reference for the effectiveness of TC. METHODS: SRs/Mas of TC therapy for KOA published before February 2023 were retrieved from eight databases in Chinese and English. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, and the Risk of Bias in Systematic (ROBIS) scale were used to assess methodological quality, reporting quality, and risk of bias. RESULTS: Seven SRs/Mas were finally included. One was deemed high quality by AMASTAR-2, while the rest were of critically low quality. In the PRISMA2020 assessment, the response rate of "Yes" for Q7, Q15, Q22, Q24, and Q27 was less than 50%. In the ROBIS assessment, three reports in Phase 3 were high risk and four were low risk. In the efficacy assessment, TC has shown varying degrees of improvement in physical function, pain, stiffness, 6-minute walk test, mental quality of life, TUG, and balance in patients with KOA. CONCLUSION: TC effectively treats KOA-associated pain, stiffness, body function, and mental quality of life. However, the low methodological quality of the studies and the high risk of migration reduced their reliability. Therefore, these conclusions should be taken with caution. High-quality, large-sample research is needed to provide stronger and more scientific evidence.

Circadian rhythm as a key player in cancer progression as well as a therapeutic target in HER2-positive advanced gastric cancer treatment.

Gastric cancer is one of the most common cancer types with less than one year prognosis in metastatic disease, which poses a huge disease burden. One of the key players in poor prognosis is human epidermal growth factor receptor 2 (HER2), which also contributes to the pathogenesis of HER2-positive advanced gastric cancer. Trastuzumab is used as first-line chemotherapy that targets the expression of HER2, however, trastuzumab resistance is an inevitable major problem. To overcome this problem, readjustment of the circadian system may play a crucial role, as dysregulation in the expression of circadian clock genes has been observed in tumors. Therefore, pharmacological modulation of clock components can be considered for better efficacy of trastuzumab. In this review, we discuss the association of circadian clock with cancer progression, development, and treatment. Metformin-based chronotherapy can disrupt BMAL1-CLOCK-PER1-HK2 axis, thereby affecting glycolysis oscillation to overcome trastuzumab resistance in HER2-positive advanced gastric cancer.

Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation.

Baicalein (5,6,7-trihydroxyflavone) is a traditional Chinese medicine with multiple pharmacological and biological activities including anti-inflammatory and anti-fibrotic effects. However, whether baicalein has a therapeutic impact on peritoneal fibrosis has not been reported yet. In the present study, network pharmacology and molecular docking approaches were performed to evaluate the role and the potential mechanisms of baicalein in attenuating peritoneal dialysis-associated peritoneal fibrosis. The results were validated in both animal models and the cultured human mesothelial cell line. Nine intersection genes among baicalein targets and the human peritoneum RNA-seq dataset including four encapsulating peritoneal sclerosis samples and four controls were predicted by network analysis. Among them, MMP2, BAX, ADORA3, HIF1A, PIM1, CA12, and ALOX5 exhibited higher expression in the peritoneum with encapsulating peritoneal sclerosis compared with those in the control, which might be crucial targets of baicalein against peritoneal fibrosis. Furthermore, KEGG and GO enrichment analyses suggested that baicalein played an anti-peritoneal fibrosis role through the regulating cell proliferation, inflammatory response, and AGE-RAGE signaling pathway. Moreover, molecular docking analysis revealed a strong potential binding between baicalein and MMP2, which was consistent with the predictive results. Importantly, using a mouse model of peritoneal fibrosis by intraperitoneally injecting 4.25% glucose dialysate, we found that baicalein treatment significantly attenuated peritoneal fibrosis, as evident by decreased collagen deposition, protein expression of α-SMA and fibronectin, and peritoneal thickness, at least, by reducing the expression of MMP2, suggesting that baicalein may have therapeutic potential in suppressing peritoneal dialysis-related fibrosis.

A near-infrared and lysosome-targeted BODIPY photosensitizer for photodynamic and photothermal synergistic therapy.

Phototherapy is a promising approach for the treatment of cancers and other diseases. So far, many photosensitizers have been developed for photodynamic therapy (PDT) or photothermal therapy (PTT). However, it remains a challenge to develop a system for synergistic PDT and PTT with specific targeting and real-time fluorescence tracking. Herein, we designed a multifunctional BODIPY derivative, Lyso-BDP, for synergistic PDT and PTT against tumors. Lyso-BDP was composed of three parts: (1) the BODIPY fluorophore was selected as a theranostic core, (2) a morpholine group modified on meso-BODIPY served as a lysosome-targeting unit for enhancing the antitumor effect, and (3) N,N-diethyl-4-vinylaniline was attached to the BODIPY core to extend its wavelength to the near-infrared region. Finally, Lyso-BDP shows near-infrared absorption and emission, photosensitizing activity, lysosomal targeting, and synergistic PDT and PTT effects, and effectively kills cancer cells both in vitro and in vivo. Therefore, our study demonstrates that Lyso-BDP can serve as a promising photosensitizer in the therapy of cancer with potential clinical application prospects.

Rose essential oil diminishes dopaminergic neuron degenerations and reduces α-synuclein aggregation in Caenorhabditis elegans models of Parkinson's disease.

Parkinson's disease (P.D.) is the second most progressive neurodegenerative disorder in the elderly. Degeneration of dopaminergic (DA) neurons and α-synuclein (α-Syn) accumulated toxicity is the major contributor to this disease. At present, the disease has no effective treatment. Many recent studies focus on identifying novel therapeutics that provide benefits to stop the disease progression in P.D. patients. Screening novel and effective drugs in P.D. animal models is time- and cost-consuming. Rose Essential Oil (REO) extracted from Rosa Rugosa species (R. Setate × R. Rugosa). REO contains Citronellol, Geraniol, and Octadiene that possess anti-Aß, anti-oxidative, and anti-depression-like properties, but no reports have defined the REO effect on P.D. yet. The present study examines the REO neuroprotective potential in transgenic Caenorhabditis elegans P.D. models. We observed that REO reduced α-Syn aggregations and diminished DA neuron degenerations induced by 6-OHDA, reduced food-sensing behavioural disabilities, and prolonged the lifespan of the nematode. Moreover, REO augmented the chymotrypsin-like proteasome and SOD-3 activities. Further, we observed the anti-oxidative role of REO by reducing internal cells ROS. Together, these findings supported REO as an anti-PD drug and may exert its effects by lowering oxidative stress via the anti-oxidative pathway.

An oxygen-carrying and lysosome-targeting BODIPY derivative for NIR bioimaging and enhanced multimodal therapy against hypoxic tumors.

Cancer treatment modalities have gradually shifted from monotherapies to multimodal therapies. It is still a challenge to develop a synergistic chemo-phototherapy system with relieving tumor hypoxia, specific targeting, and real-time fluorescence tracking. In this study, we designed a multifunctional BODIPY derivative, FBD-M, for synergistic chemo-phototherapy against hypoxic tumors. FBD-M was composed of four parts: 1) The BODIPY fluorophore selected as a theranostic core, 2) A pentafluorobenzene group modified on meso-BODIPY to carry oxygen, 3) A morpholine group hooked to one side of BODIPY served as a lysosome-targeting unit for enhancing antitumor effect, and 4) An aromatic nitrogen mustard group introduced on other side of BODIPY to achieve chemotherapy. After introducing the morpholine and aromatic nitrogen mustard in BODIPY, the conjugate system of BODIPY was also expanded to realize near-infrared (NIR) phototherapy. Finally, FBD-M was obtained by a rational design, which possessed with NIR absorbance and emission, photosensitive activity, oxygen-carrying capability for relieving tumor hypoxia, high photothermal conversion efficiency, good photostability, lysosome targeting, low toxicity, and synergistic chemo-phototherapy against hypoxic tumors. FBD-M had been successfully applied for anticancer in vitro and in vivo. Our study demonstrates that FBD-M can serve as an ideal multifunctional theranostic agents.

Efficacy of Tailor-Made Notched Music Training Versus Tinnitus Retraining Therapy in Adults With Chronic Subjective Tinnitus: A Randomized Controlled Clinical Trial.

OBJECTIVES: Chronic subjective tinnitus can have a serious effect on daily life, even causing serious psychological disorders. Currently there are no specific effective solutions or cures. Tailor-made notched music training (TMNMT) is a recently proposed sound therapy that has simpler processes and a higher compliance rate than tinnitus retraining therapy (TRT), a widely used treatment for chronic subjective tinnitus. This study explores the therapeutic effect of TMNMT in comparison to TRT to highlight its clinical value. DESIGN: The study was a randomized controlled, single-blinded clinical trial. One hundred twenty eligible participants were randomly assigned to receive TMNMT (n = 60) or TRT (n = 60) for 3 mo with concurrent follow-up. It should be noted that the duration of sound treatment in TRT was modified to 2 hr per day for better feasibility in practice. The primary outcome was mean change in tinnitus handicap inventory (THI) measured at baseline ( T0 ), 1 mo ( T1 ) and 3 mo ( T2 ) after intervention. Change in visual analog scale (VAS) was measured as a secondary outcome. A comparison of therapeutic effectiveness between TMNMT and TRT was evaluated by repeated measure analysis of variance. RESULTS: One hundred and twelve (93%) of participants took part in the study, of which 64 were men and 48 women. Mean (SD) age was 42.80 (12.91) years. Fifty-eight were allocated to receive TMNMT and 54 to receive TRT. The between-group difference in primary outcome was -6.90 points (95% confidence interval [CI], -13.53 to -0.27) at T1 and -6.17 points (95% CI, -13.04 to 0.71) at T2 . These results closely reached to clinical significance of tinnitus-related effective relief. For the secondary outcome, the mean value in the TMNMT group was 0.83 points (95% CI, 0.12 to 1.54), significantly lower than the mean value of the TRT group. The differences in THI and VAS between the two groups were statistically significant after intervention. Further analysis showed that age and baseline THI and VAS scores were associated with change in THI and VAS scores after interventions. CONCLUSIONS: Both TMNMT and TRT were able to alleviate chronic subjective tinnitus effectively after a 3 month intervention. When the two forms of therapy were compared TMNMT appeared to be more effective and consequently potentially superior to TRT for reducing tinnitus loudness and functional and emotional disturbance associated with chronic subjective tinnitus.

Mechanism and Active Components of Qingre Lidan Tablets Alleviate Intrahepatic Cholestasis by Activating the Farnesoid X Receptor.

Background: Qingre Lidan tablets (QLTs) are a compound preparation of Chinese medicine that have long been used clinically to treat poor bile circulation caused by the inflammation and obstruction of the gallbladder and bile duct and to relieve jaundice and other symptoms. However, its material basis and mechanism are still unclear. The purpose of this study was to investigate the mechanism and active components of QLTs for treating intrahepatic cholestasis (IHC) in rat models. Methods: In vivo experiments verified the effect of QLTs on alpha-naphthyl isothiocyanate (ANIT)-induced IHC models in rats. The mRNA and protein expression levels of farnesoid X receptor (FXR), bile salt export pump (BSEP), and multidrug-associated protein 2 (MRP2) in the rat liver were detected. UPLC/Q-TOF-MS was used to separate and identify the monomers in QLTs, and a dual-luciferase reporter assay was used to select effective the monomers that stimulate FXR. Among the selected monomers, baicalein was used as a representative to verify the effect on rat IHC models. Results: QLTs and baicalein significantly reduced the serum biochemical indicators reflecting the changes in liver function among IHC rats and remitted the ANIT-induced liver histopathological changes. The expression levels of FXR, BSEP, and MRP2 in the liver were significantly increased after QLT treatment in a dose-dependent manner. Moreover, six types of active components that activate FXR were selected in QLTs, namely baicalein, wogonin, baicalein II, emodin, dibutyl phthalate, and diisooctyl phthalate. Conclusions: QLTs and the active component, baicalein, can alleviate IHC in model rats.

Effectiveness and safety of Tai Chi for anxiety disorder of COVID-19: A protocol of systematic review and meta-analysis.

BACKGROUND: Anxiety disorders pose a significant threat to the clinical rehabilitation of patients with coronavirus disease 2019 (COVID-19). Tai Chi is a therapeutic exercise that can be used to treat anxiety disorders. We aim to conduct a systematic review and meta-analysis to evaluate the effectiveness and safety of Tai Chi for treating patients with anxiety disorders caused by COVID-19. METHODS: The PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, Wan Fang, and Chinese Clinical Trial Registry databases will be searched for reports of randomized controlled trials on Tai Chi for the treatment of anxiety disorders caused by COVID-19, published from December 1, 2019, to August 22, 2022. Two researchers will screen the articles and extract the relevant information. RESULTS: The results will provide a systematic overview of the current evidence on the use of Tai Chi to treat anxiety disorders caused by COVID-19 among patients. CONCLUSION: The conclusions of this study will help clarify whether Tai Chi is effective and safe for treating anxiety disorders caused by COVID-19.

Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis.

Objective: The aim of this study was to evaluate the comparison between acupuncture combined with metformin versus metformin alone in improving the pregnancy rate of people with polycystic ovary syndrome (PCOS). Methods: A literature search of eight databases resulted in nine randomized controlled trials (RCTs) that assessed the effect of acupuncture combined with metformin on pregnancy rate in PCOS patients compared with metformin alone. Subsequently, data extraction and analysis were conducted to evaluate the quality and risk of bias of the methodological design of the study, and meta-analysis was conducted on the RCT data. Results: Nine RCTs and 1,159 women were included. Acupuncture can improve pregnancy rate. It was analyzed according to the diagnostic criteria of PCOS [Z = 2.72, p = 0.007, relative risk (RR) 1.31, 95% CI 1.08 to 1.60, p = 0.15, I 2 = 41%]. Analysis was performed according to different diagnostic criteria of pregnancy (Z = 3.22, p = 0.001, RR 1.35, 95% CI 1.13 to 1.63, p = 0.12, I 2 = 42%). Acupuncture can improve ovulation rate. Subgroup analysis was performed according to the number of ovulation patients (Z = 2.67, p = 0.008, RR 1.31, 95% CI 1.07 to 1.59, p = 0.04, I 2 = 63%) and ovulation cycle (Z = 3.57; p = 0.0004, RR 1.18, 95% CI 1.08 to 1.29, p = 0.57, I 2 = 0%). Statistical analysis also showed that acupuncture combined with metformin could improve homeostatic model assessment of insulin resistance (HOMA-IR) [mean difference (MD) -0.68, 95% CI -1.01 to -0.35, p = 0.003, I 2 = 83%]. Conclusions: Based on the results of this study, compared with metformin alone, acupuncture combined with metformin has a positive effect on pregnancy rate, ovulation rate, and insulin resistance in PCOS. However, due to the limitations regarding the number and quality of the included studies, the above conclusions need to be verified by further high-quality studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero.

Black mulberry (Morus nigra) fruit extract alleviated AD-Like symptoms induced by toxic Aß protein in transgenic Caenorhabditis elegans via insulin DAF-16 signaling pathway.

Alzheimer's disease (AD) is one of the most severe neurodegenerative disorders. Recently, there is no effective treatment drug for AD. Morus nigra (M. nigra) is a black mulberry and widely distributed fruit in the Moraceae family with various undiscovered biological activities. The study aimed to investigate the potential anti-AD effect of M. nigra. Mulberry fruit extract (MF) was obtained from M. nigra and treated up to 1.00 mg/mL on transgenic AD Caenorhabditis elegans (C. elegans) models. MF inhibited Amyloid-ß (Aß)-induced paralysis symptoms by about 55.65 %, reduced Aß accumulation more than 50 % via immunoblotting, and suppressed over-sensitivity to exogenous serotonin in C. elegans. Furthermore, MF decreased the Aß oligomeric depositions in worm CL2006. MF activated the DAF-16 nuclear translocation and its downstream SOD-3 and GST-4. AD is a major age-related disorder. Therefore, MF treated for an aging test and proved to be expanded the lifespan of the worms up to 34.7 %. Besides, we have evaluated the MF in vivo antioxidative properties, where MF reduced reactive oxygen species (ROS) generations in C. elegans and remitted the activation of HSP-16.2 induced by the oxidative action of Juglone. Gene knockout and extended the lifespan of AD worms. However, RNA interference (RNAi) successfully silenced the daf-16 on the Aß phenotypic paralysis proved by MF effect. Our results indicate that MF alleviates AD-Like symptoms by activating the DAF-16 insulin signal pathway in C. elegans. Therefore, this MF study may provide new insights for mulberry application in safe AD treatment and clinical study.

Comparison and Characterization of the Structure and Physicochemical Properties of Three Citrus Fibers: Effect of Ball Milling Treatment.

Effects of ball milling (BM) on the structure and physicochemical properties of three types of citrus fibers were investigated. With the extension of the grinding time, the particle size of citrus fibers significantly decreased. Fourier transform infrared spectroscopy (FTIR) showed that the three citrus fibers had similar chemical groups, and more -OH and phenolic acid groups were exposed after BM, and pectin and lignin were not degraded. Scanning electron microscope (SEM) results showed that the appearance of particles changed from spherical to fragmented, irregular shapes. The water holding capacity (WHC), oil holding capacity (OHC), and water swelling capacity (WSC) of citrus fibers LM, JK, and FS reached the maximum value after BM of 2 h (increasing by 18.5%), 4 h (increasing by 46.1%), and 10 h (increasing by 38.3%), respectively. After 10 h BM, citrus fibers FS and JK had the highest adsorption capacity of cholesterol and sodium cholate, increasing by 48.3% and 48.6%, respectively. This indicates that BM transforms the spatial structure of citrus fibers and improves their physicochemical properties.

Effects of an Armillaria mellea Polysaccharide on Learning and Memory of D-Galactose-Induced Aging Mice.

Arm illaria mellea has been known and used in traditional medicine in East Asia for hundreds of years. It has already been reported that A. mellea extracts have various pharmacological effects, and the polysaccharides of A. mellea exhibit antioxidant and anti-apoptotic activities. In this study, a water-soluble polysaccharide (AMP-N-a-1), with an average molecular weight of 17 kD, was isolated and purified from the water extract of A. mellea using DEAE-52, Sepharose CL-4B, and Sephadex G-100 column chromatography. AMP-N-a-1 was mainly composed of Man (1.65%), Glca (1.64%), Rha (1.82%), Gala (2.49%), Glc (90.48%), Gal (0.89%), Xyl (0.42%), and Ara (0.61%). AMP-N-a-1 was used to study the effect on the learning and memory of mice and its underlying mechanisms. The results showed that AMP-N-a-1 could significantly increase the activities of catalase (CAT) and superoxide dismutase (SOD) and reduce the content of nitric oxide (NO) in mouse brain tissue. Meanwhile, AMP-N-a-1 could reduce the contents of norepinephrine (NE) and dopamine (DA) but could increase the content of 5-hydroxytryptamine (5-HT) in mouse brain tissue. In addition, the immunofluorescence experiment showed that AMP-N-a-1 could promote the proliferation of hippocampal dentate gyrus neurons. The above results indicate that AMP-N-a-1 can significantly improve the learning and memory of mice, and the mechanism may be that AMP-N-a-1 can participate in the regulation of learning and memory through a variety of ways.

Impact of insufficient doses of medications on Helicobacter pylori eradication: a retrospective observational study.

BACKGROUND AND AIMS: The doses of medications may influence the success of Helicobacter pylori (H. pylori) eradication. This real-world observational study aimed to explore the impact of insufficient doses of medications prescribed for the bismuth-containing quadruple therapy (BQT) regimen on successful H. pylori eradication. METHODS: We retrospectively screened the patients who were diagnosed with H. pylori infection and received BQT regimens for H. pylori eradication at our department between January 2017 and July 2020. The rate of successful H. pylori eradication was compared according to the doses of medications prescribed. Standard doses were defined according to the clinical guidelines. RESULTS: Overall, 1054 patients were included. The rate of successful H. pylori eradication was 78.2% (824/1054). Among them, proton pump inhibitors (PPIs) and antibiotics were prescribed at insufficient doses in 37.0% (390/1054) and 6.7% (71/1054) of patients, respectively. Furthermore, pantoprazole (98.7% [385/390]) was the most common type of PPIs prescribed at insufficient doses, and nitroimidazoles (85.9% [61/71]) were the most common type of antibiotics prescribed at insufficient doses. Among the patients receiving colloidal bismuth pectin (CBP) (200 mg tid) and standard-dose antibiotics, the rate of successful H. pylori eradication was lower in insufficient-dose PPIs group than standard-dose PPIs group (78.1% [271/347] versus 82.6% [438/530], P = 0.095). Among the patients receiving CBP (200 mg tid) and standard-dose PPIs, the rate of successful H. pylori eradication was significantly lower in insufficient-dose antibiotics group than standard-dose antibiotics group (37.8% [14/37] versus 82.6% [438/530], P < 0.0001). Among the patients receiving CBP 200 mg tid, the rate of successful H. pylori eradication was significantly lower in patients receiving both PPIs and antibiotics at insufficient doses than those at standard doses (46.4% [13/28] versus 82.6% [438/530], P < 0.0001). CONCLUSION: Among the BQT regimens, PPIs and/or antibiotics, especially pantoprazole and metronidazole, are often prescribed at insufficient doses, compromising the success of H. pylori eradication. ABBREVIATIONS: H. pylori, Helicobacter pylori; UBT, urea breath test; DPM, disintegrations per minute; BQT, bismuth-containing quadruple therapy; PPI, proton pump inhibitor; CBP, colloidal bismuth pectin; qd, once daily; bid, twice daily; tid, three times daily; qid, four times daily.