Anti-inflammatory effect and pharmacokinetics of dehydroandrographolide, an active component of Andrographis paniculata, on Poly(I:C)-induced acute lung injury.

Acute lung injury (ALI) is a common and critical respiratory disorder caused by various factors, with viral infection being the leading contributor. Dehydroandrographolide (DAP), a constituent of the Chinese herbal plant Andrographis paniculata, exhibits a range of activities including anti-inflammatory, in vitro antiviral and immune-enhancing effects. This study evaluated the anti-inflammatory effects and pharmacokinetics (PK) profile of DAP in ALI mice induced by intratracheal instillation of Poly(I:C) (PIC). The results showed that oral administration of DAP (10-40 mg/kg) effectively suppressed the increase in lung wet-dry weight ratio, total cells, total protein content, accumulation of immune cells, inflammatory cytokines and neutrophil elastase levels in bronchoalveolar lavage fluid of PIC-treated mice. DAP concentrations, determined by an LC-MS/MS method, in plasma after receiving DAP (20 mg/kg) were unchanged compared to those in normal mice. However, DAP concentrations and relative PK parameters in the lungs were significantly altered in PIC-treated mice, exhibiting a relatively higher maximum concentration, larger AUC, and longer elimination half-life than those in the lungs of normal mice. These results demonstrated that DAP could improve lung edema and inflammation in ALI mice, and suggested that lung injury might influence the PK properties of DAP, leading to increased lung distribution and residence. Our study provides evidence that DAP displays significant anti-inflammatory activity against viral lung injury and is more likely to distribute to damaged lung tissue.

Shen Yuan extract exerts a hypnotic effect via the tryptophan/5-hydroxytryptamine/melatonin pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.

Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8+ T cells.

Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer cells may preferentially rely on certain amino acids for rapid growth and metastasis. On the other hand, sufficient nutrient availability and uptake are necessary for mounting an effective T cell anti-tumor response in the tumor microenvironment (TME). Here we demonstrate that tumor cells outcompete T cells for cystine uptake due to high Slc7a11 expression. This competition induces T-cell exhaustion and ferroptosis, characterized by diminished memory formation and cytokine secretion, increased PD-1 and TIM-3 expression, as well as intracellular oxidative stress and lipid-peroxide accumulation. Importantly, either Slc7a11 deletion in tumor cells or intratumoral cystine supplementation improves T cell anti-tumor immunity. Mechanistically, cystine deprivation in T cells disrupts glutathione synthesis, but promotes CD36 mediated lipid uptake due to dysregulated cystine/glutamate exchange. Moreover, enforced expression of glutamate-cysteine ligase catalytic subunit (Gclc) promotes glutathione synthesis and prevents CD36 upregulation, thus boosting T cell anti-tumor immunity. Our findings reveal cystine as an intracellular metabolic checkpoint that orchestrates T-cell survival and differentiation, and highlight Gclc as a potential therapeutic target for enhancing T cell anti-tumor function.

Complementary and alternative therapies for symptom clusters in cancer patients:a scoping review / 现代临床护理

Objective To identify the characteristics of complementary and alternative therapies for cancer patients and investigate the effect on symptom clusters in cancer patients,in order to provide references in management of the symptom clusters.Methods A scoping review was conducted to search nine databases,namely PubMed,Cochrane Library,Web of Science,Embase,PsycINFO,CINAHL,CNKI,Wanfang Data,and VIP,for literatures published between January 2016 and January 2024.Results Twenty articles focusing on complementary and alternative therapies were included.Four themes were identified from the retrieved articles:cancer research subjects,characteristics of complementary alternative therapies,type of symptom cluster and effectiveness of complementary alternative therapies.Specifically,the cancer research subjects in relation to symptom cluster management included those of breast cancer,advanced cancer and the cancer under radio or chemotherapy.The most commonly used types of complementary and alternative therapies in managing the symptom clusters were exercise therapies,cognitive-behavioural interventions,traditional Chinese medicine therapies,multidisciplinary collaborative models and specific interventions.Interventions for symptom clusters predominantly targeted fatigue,mental status,pain,and gastrointestinal symptoms.Conclusion The interventions for symptom clusters in complementary and alternative therapies vary across different types of complementary and alternative therapies,so as the effectiveness.Some of the complementary and alternative therapies have unidentified effects and further investigations are required.The complementary and alternative therapies currently that have been used in managing the symptom clusters were found to have shortcomings.Further studies should focus on sentinel and core symptoms of symptom clusters and emphasize the development of standardised and individualised intervention plans based on symptom management theories,hence to improve the management of symptom clusters in cancer patients.

Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis.

BACKGROUNDS: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. METHODS: The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. RESULTS: LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1ß, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. CONCLUSIONS: LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.

Efficacy of coenzyme Q10 supplementation for male infertility with high sperm DNA fragmentation index: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Infertility is a focal issue in public health and affects human reproduction and survival. Notably, an increasing number of studies in recent decades have found that sperm DNA integrity plays a critical role in the development of healthy embryos. Among the multiple pathogenic factors of sperm DNA fragmentation, oxidative stress has proven to be predominant. Coenzyme Q10 supplementation, which has been used for the treatment of male infertility, has shown good clinical efficacy due to its oxidation resistance, but its efficacy as measured by the sperm DNA fragmentation index remains controversial. To address this issue, we will perform a systematic review and meta-analysis to evaluate the efficacy of coenzyme Q10 for male infertility patients with a high sperm DNA fragmentation index. METHODS AND ANALYSIS: The PubMed, Embase, Cochrane Central Register of Studies and Web of Science databases will be comprehensively searched from inception to 31 December 2022 to identify relevant studies published in the English language using appropriate search strategies. The search terms will be derived from the following concepts: sperm DNA fragmentation, coenzyme Q10 and randomised controlled trials. Two review stages, that is, title and abstract screening and full-text screening, will be performed by two reviewers. The risk of bias, publication bias and evidence grade of the included studies will be assessed using a standardised protocol. Data will be used to calculate effect sizes. Heterogeneity among the studies will be evaluated graphically. Subgroup analysis and sensitivity analysis will be performed if necessary to validate the results. ETHICS AND DISSEMINATION: No ethical approval will be needed, as there will be no participants in this study. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the findings through publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42022293340.

The effect of acupuncture on oxidative stress: A systematic review and meta-analysis of animal models.

INTRODUCTION: Oxidative stress is involved in the occurrence and development of multiple diseases. Acupuncture shows an excellent clinical efficacy in practical application but its mechanism remains unclear. This systematic review and meta-analysis was aimed at assessing the effect of acupuncture on oxidative stress in animal models. METHODS: PubMed, Embase, and Web of Science database were retrieved for randomized controlled trials about acupuncture on oxidative stress in animal models from inception to August 2021. Two reviewers independently screened and extracted articles according to inclusion and exclusion criteria. We used the mean difference (MD)/standardized mean difference (SMD) to perform an effect size analysis and selected fixed-effect or random-effect models to pool the data, depending on a 95% confidence interval (CI). RESULTS: A total of 12 studies comprising 125 samples were included in the quantitative meta-analysis. Compared with sham acupuncture, acupuncture (manual acupuncture, electropuncture, and laser acupuncture) reduced the level of malondialdehyde (SMD, -3.03; CI, -4.40, -1.65; p < 0.00001) and increased the levels of superoxide dismutase (SMD, 3.39; CI, 1.99, 4.79; p < 0.00001), glutathione peroxidase (SMD, 2.21; CI, 1.10, 3.32; p < 0.00001), and catalase (SMD, 2.80; CI, 0.57, 5.03; p = 0.01). CONCLUSION: This meta-analysis indicated that acupuncture can regulate oxidative stress by lowering the lipid peroxidation and activating the antioxidant enzyme system. In consideration of heterogeneity between studies, future studies should be performed by complying with strict standards and increasing sample size in animal experiments to reduce bias.

Acupuncture for Female Infertility: Discussion on Action Mechanism and Application.

A higher incidence of female infertility has been reported with an unexpectedly early appearance in recent years. The female infertility treatment and application of assisted reproductive technology have recently gained immense interest from scientists. Many studies have discussed the beneficial effects of acupuncture on female infertility. With advancements in science and medical technology, acupuncture-related research has increased in investigating its effectiveness in treating female infertility. This review focuses on a compilation of research in recent years on acupuncture for female infertility treatment and the exploration of the underlying mechanism. For this purpose, literature was searched using various search engines like PubMed, Web of Science, and Google Scholar. The search was refined by only focusing on recent studies on acupuncture effectiveness and mechanism in female infertility and evaluating pregnancy outcomes.

Efficacy and Safety of the Bushen-Shugan Method in Pregnancy Outcomes in Patients with Recurrent Miscarriage Complicated by Anxiety and Depression: A Prospective Randomized Trial.

Objective: This study aimed to investigate the effect of the Bushen-Shugan (BSSG) method on pregnancy outcomes, serum D-dimer (D-D), platelet aggregation rate, homocysteine (Hcy) and antithrombin III (AT-III) in patients with recurrent miscarriage complicated by anxiety and depression. Methods: From December 2016 to December 2019, 100 patients with recurrent miscarriage combined with anxiety and depression were enrolled in our study, and a prospective randomized trial was carried out. Patients were randomly assigned to either the control group or the BSSG group via the random number table method. Traditional Chinese medicine (TCM) syndrome scores, laboratory indicators and psychological changes were compared in the 2 groups before and after treatment. Results: After treatment, the primary, secondary and total TCM syndrome scores in the 2 groups were lower, and the scores in the BSSG group were significantly lower than in the control group. The clinical curative effect in the BSSG group was significantly higher (92% vs 76%) than in the control group. The levels of ß-HCG, P, E2 and AT-III in the 2 groups were higher, while levels of D-D, platelet aggregation rate and Hcy were lower than before treatment. The Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were lower after treatment in both groups, and the scores in the BSSG group were significantly lower than in the control group. Conclusions: The BSSG method may be worthy of consideration because it improves pregnancy outcomes in patients with recurrent miscarriage complicated by anxiety and depression.

Stilbenes from the leaves of Cajanus cajan and their in vitro anti-inflammatory activities.

Eighteen stilbenes (1-18), including six previously undescribed ones (1-6), with diverse modification patterns were isolated from the leaves of edible and medicinal plant Cajanus cajan. Among the new isolates, compounds 1-3 were initially obtained as three racemic mixtures, which were further resolved into three pairs of optically pure enantiomers, respectively, by chiral HPLC. Besides, compounds 8, 10, 11, and 18 were obtained from C. cajan for the first time. The chemical structures and absolute configurations of the new stilbenes were elucidated unambiguously on the basis of extensive spectroscopic analyses, single crystal X-ray crystallographic study, and quantum chemical electronic circular dichroism (ECD) calculations. In addition, the in vitro anti-inflammatory activities of all isolated stilbenes were evaluated. Compounds 2, 9, 10, 11, and 14 exerted moderate suppression of nitric oxide (NO) secretion in lipopolysaccharide (LPS)-induced RAW264.7 cells without exhibiting substantial cytotoxicity.

Effects of temperature and ferric ion on the formation of glycerol core aldehydes during simulated frying.

Glycerol core aldehydes (GCAs) are toxins widely formed in oils at high temperature. This study investigated the effects of frying time, temperature, and Fe3+ content on the GCAs formation in high-oleic sunflower oil. The results showed that the GCAs (8-oxo, 9-oxo, 10-oxo-8, 11-oxo-9) concentrations increased with time following the pseudo-first-order kinetics. Frying at 160 °C without Fe3+ and at 180 °C with 0.0005 mol·L-1 Fe3+ yielded the lowest and highest total GCA content. The concentrations of GCAs (8-oxo) and GCAs (9-oxo) or GCAs (10-oxo-8) and GCAs (11-oxo-9) changed similarly with different frying temperature and Fe3+ concentration. The major GCAs was GCAs (9-oxo) (40-70%), which also had the highest formation rate (5.42 × 10-4 mg·g-1·h-1). However, GCA (10-oxo-8) and GCAs (11-oxo-9) with similar proportion (ca. 10-20%) and GCAs (8-oxo) made up the least proportions (<10%).

Pulmonary arterial hypertension and flavonoids: A role in treatment.

Pulmonary arterial hypertension (PAH) is a high mortality progressive pulmonary vascular disease that can lead to right heart failure. The use of clinical drugs for the treatment of PAH is limited to a great extent because of its single target and high price. Flavonoids are widely distributed in nature, and have been found in fruits, vegetables, and traditional Chinese medicine. They have diverse biological activities and various pharmacological effects such as antitumor, antioxidation, and anti-inflammatory. This review summarizes the progress in pharmacodynamics and mechanism of flavonoids in the treatment of PAH in recent years, in order to provide some theoretical references for relevant researchers.

Transcriptomic study of the mechanism by which the Kai Yu Zhong Yu recipe improves oocyte quality in a stressed mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Kai Yu Zhong Yu recipe (KYZY) is a classic herbal formula in traditional Chinese medicine (TCM) that has been used to treat infertility associated with psychological stress for more than three hundred years. AIM OF THE STUDY: Psychological stress has major impacts on fertility, with variable outcomes depending on the nature, strength, and duration of the stress. Stress can directly disturb ovulation, oocyte quality, maturation, and embryo development. The aim of this study is to investigate the molecular mechanism by which KYZY improves oocyte developmental potential under psychological stress. MATERIALS AND METHODS: ICR female mice aged 4-5 weeks were randomly divided into five groups: control, stressed in the chronic unpredictable stress model (CUSM), and stressed plus KYZY treatment at 38.2 g/kg (KYZYH), 19.1 g/kg (KYZYM), or 9.6 g/kg (KYZYL). Ovary function was assessed by measuring serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH). Oocyte quality was evaluated in terms of reactive oxygen species (ROS) levels, apoptotic DNA fragmentation, and mitochondria distribution. We used RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) between groups and then further analyzed the DEGs for gene ontology (GO) term enrichment and protein-protein interactions. RESULTS: Mice in the stressed group had reduced serum E2, LH, and FSH as well as increased ROS levels, increased apoptosis, and disturbed mitochondria distribution in oocytes. Treatment with KYZY at all three doses reversed or ameliorated these negative effects of stress. DEG analysis identified 187 common genes between the two comparisons (stressed vs. control and KYZYM vs. stressed), 33 of which were annotated with six gene ontology (GO)'s biological process (BP) terms: cell differentiation, apoptosis, ATP synthesis, protein homo-oligomerization, neuron migration, and negative regulation of peptidase activity. Protein-protein interaction network analysis of DEGs identified key hub genes. Notably, the genes Atp5o and Cyc1 were both involved in the ATP synthesis and among the top three hub genes, suggesting that regulation of oocyte mitochondrial electron transport and ATP synthesis is important in the response to stress and also is a possible mechanism of action for KYZY. CONCLUSIONS: KYZY was effective in ameliorating the adverse effects of stress on oocyte competence, possibly by targeting the mitochondrial respiratory chain and ATP synthase.

Xanthohumol ameliorates memory impairment and reduces the deposition of ß-amyloid in APP/PS1 mice via regulating the mTOR/LC3II and Bax/Bcl-2 signalling pathways.

OBJECTIVES: Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. METHODS: APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aß in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. KEY FINDINGS: Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1ß levels both in serum and hippocampus. Xanthohumol also significantly reduced Aß deposition in the hippocampus and activated autophagy and anti-apoptotic signals. CONCLUSIONS: Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.

Identification of the metabolites produced following Iris tectorum Maxim oral administration and a network pharmacology-based analysis of their potential pharmacological properties.

1. Iris tectorum Maxim is a traditional herbal medicine that has been used to treat cancer, abdominal distension, hepatic cirrhosis, and inflammatory diseases. How I. tectorum Maxim is metabolised and the mechanistic basis for its pharmacological activity remain to be defined.2. This study was designed to clarify the metabolism of I. tectorum Maxim and to explore the mechanistic basis for its pharmacological activity.3. In the present study, 51 metabolites were identified via mass spectrometry in samples of bile, urine, and faeces from Wistar rats. Metabolites were mainly formed by glucuronidation, sulphation, methylation, and amino acid conjugation.4. Tectoridin, tectorigenin, irigenin, iristectorigenin A, iristectorigenin B, and 6-hydroxygenistein were identified as potentially be bioactive candidate metabolites for which 36 putative targets and 90 interactions were detected through a network pharmacology analysis. Gene set enrichment analyses and compound-disease networks revealed the targets of these metabolites to regulate important proteins associated with cancer as well as cardiovascular, urogenital, and digestive system diseases.5. Molecular docking confirmed the interactions of these six candidate bioactive metabolites with carbonic anhydrase IV, VII, and XII.6. Overall, these data offer new insights into the metabolism and pharmacological activity of I. tectorum Maxim in vivo.

[Retrospective analysis on pregnancy outcomes and fat-related factors of treatment of endomorph PCOS infertility patients by acupuncture of 8 acupoints around umbilicus].

OBJECTIVE: To assess the therapeutic effect of acupuncture of eight acupoints around the umbilicus in improving the metabolic level and reproductive function in endomorph polycystic ovary syndrome (PCOS) infertile patients. METHODS: Retrospective analysis was performed on 96 cases of endomorph type PCOS infertility patients who were admitted to the clinic of the Reproductive Center of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from October 2015 to June 2018. Among them, fifty-six cases of the acupuncture group received treatment with acupuncture stimulation of eight acupoints (Shuifen ï¼»CV9ï¼½, Yinjiao ï¼»CV7ï¼½, Tianshu ï¼»ST25ï¼½, Wailing ï¼»ST26ï¼½, Huaroumen ï¼»ST24ï¼½, etc.) around the umbilicus, and 40 cases of the control group were treated by oral administration of Letrozole. Acupuncture was performed once every other day, and Letrozole (2.5 mg/day) given once daily for 5 days, if no pregnancy got, the treatment procedure was repeated once again next menstruation cycle, continuously for 3 months. The pregnancy outcomes including the pregnancy rate, persistent pregnancy rate, ovulation rate and the first trimester abortion rate, and the levels of fat-related factors including body mass index (BMI), waist-to-hip ratio (WHR), homeostasis model of insulin resistance (HOMA-IR=fasting insulin x fasting blood glucose /22.5), leptin(LEP) and adiponectin(APN) of the two groups were compared. The ovulation rate (number of effective ovulation cycles/ number of observation cycles) x 100%, the first trimester abortion rate (number of spontaneous abortion within 12 weeks÷pregnancy cases) X100% were calculated. The fasting blood samples were taken for assaying serum LEP and APN contents using ELISA, blood glucose level using hexokinase assay, and serum insulin by using chemiluminescent microparticle immunoassay, separately. RESULTS: After the treatment, the pregnancy rate and the level of APN were significantly higher (P<0.05), and the BMI, WHR, HOMA-IR and LEP levels were all obviously lower in the acupuncture group than in the control group (P<0.05). There were no significant differences between the two groups in the persistent pregnancy rate, abortion rate and ovulation rate (P>0.05). CONCLUSION: Acupuncture at the eight points around the umbilicus can raise the pregnancy rate in obese type PCOS patients, which may be related to its effects in up-regulating serum APN and lowering BMI, WHR, HOMA-IR, and serum LEP levels.

Arsenic, Cadmium, Lead, and Mercury in Lactation Foods and Prenatal Vitamins: Potentially Avoidable Exposure for Breastfeeding Mothers and Infants.

Background: Human milk is a biofluid that can contain heavy metals such as arsenic, cadmium, lead, and mercury. These toxins can adversely affect endocrine, respiratory, immune, and nervous systems. Infants may have higher dietary arsenic exposure than adults due to their more restricted diets and greater intake per unit body mass. We identified commonly purchased vitamins, lactation bars, and supplements, to measure the concentration of heavy metals. The goal of the study was to measure and determine if vitamins and lactation foods could be a source of exposure. Methods: We tested 9 popular vitamins and 16 lactation bars and supplements all marketed toward breastfeeding mothers to determine the presence of heavy metals. All vitamins, bars, and supplements were analyzed using inductively coupled plasma mass spectrometry, for the total concentration of arsenic, mercury, cadmium, and lead, with the lowest detection limit of 0.001 µg/L. Results: The majority of the samples had total arsenic levels below detectable quantities (detection limit of 1 part per trillion [0.001 µg/L]), one sample of syrup had a concentration of 0.112 ± 0.005, 0.132 ± 0.009, and 0.108 ± 0.010 µg of arsenic/g. We also tested nine popular prenatal vitamins for the amount of arsenic in one serving of vitamins per day and showed exposure to arsenic in one vitamin of 7.108 µg of arsenic/day. All lactation foods and vitamins tested had undetectable amounts of cadmium, mercury, and lead. Conclusion: Most of the vitamins and bars that were tested had below the detectable limit of arsenic, cadmium, lead, and mercury; we did find one vitamin and one rice syrup that had significantly higher levels. Our data suggest that it is highly feasible to manufacture vitamins and lactation foods and supplements with significantly lower concentrations of heavy metals.

Nanotoxicology and Nanomedicine: The Yin and Yang of Nano-Bio Interactions for the New Decade.

Nanotoxicology and nanomedicine are two sub-disciplines of nanotechnology focusing on the phenomena, mechanisms, and engineering at the nano-bio interface. For the better part of the past three decades, these two disciplines have been largely developing independently of each other. Yet recent breakthroughs in microbiome research and the current COVID-19 pandemic demonstrate that holistic approaches are crucial for solving grand challenges in global health. Here we show the Yin and Yang relationship between the two fields by highlighting their shared goals of making safer nanomaterials, improved cellular and organism models, as well as advanced methodologies. We focus on the transferable knowledge between the two fields as nanotoxicological research is moving from pristine to functional nanomaterials, while inorganic nanomaterials - the main subjects of nanotoxicology - have become an emerging source for the development of nanomedicines. We call for a close partnership between the two fields in the new decade, to harness the full potential of nanotechnology for benefiting human health and environmental safety.

Humulus lupulus L. Extract Prevents Ovariectomy-Induced Osteoporosis in Mice and Regulates Activities of Osteoblasts and Osteoclasts.

OBJECTIVE: To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice. METHODS: In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed. RESULTS: Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05). CONCLUSION: HLE may protect against bone loss, and have potentials in the treatment of osteoporosis.

Preparation and in Vitro Antitumor Study of Two-Dimensional Muscovite Nanosheets.

Inorganic nanosheets are endowed with many two-dimensional (2D) morphological features including ultra-high specific surface area, ultra-thin thickness, easy functionalization, and so on. They push forward an immense influence on effective cancer diagnosis and therapy, overcoming the inherent limitations of traditional treatment methods. However, long-term toxicity and poor biocompatibility are the critical issues for most inorganic nanosheets, which hinder their further oncological applications and clinical translations. Muscovite, also named white mica (WM), an aluminosilicate, is a major component of traditional Chinese medicine, which can be exfoliated into 2D nanosheets and expected to be a potential drug carrier. In this study, WM powder was exfoliated to prepare WM nanosheets (WMNs) through a polyamine intercalation method. In addition, doxorubicin hydrochloride (Dox) was loaded to WMNs via physical adsorption and electrostatic interaction to prepare Dox-loaded WMNs (Dox@WMNs). Then, we studied that Dox@WMNs released Dox in phosphate buffer saline. We also studied the cellular uptake and cytotoxicity of Dox@WMNs in vitro. The results illustrated that Dox@WMNs cumulatively released Dox much faster and more at acidic pH (6.0 and 4.6) compared with that at physiological pH. In addition, WMNs showed selective cytotoxicity. Within a certain concentration range, WMNs were cytotoxic to Hela cells but non-cytotoxic to RAW 264.7 cells. Compared with cytotoxicity at pH 7.4, the cytotoxicity of Dox@WMNs was significantly enhanced at pH 6.4 and 4.6. WMNs mainly promoted the immunostimulatory polarization of RAW 264.7 cells into M1 macrophages.