Statin use as a moderator on the association between metformin and breast cancer risk in women with type 2 diabetes mellitus.

INTRODUCTION: Metformin and statins are considered as potential agents for prevention of breast cancer, however, existing evidence does not uniformly substantiate this claim, and the data is scarce concerning their interaction in relation to breast cancer risk. This study aims to investigate whether the effect of metformin on breast cancer incidence varied by statin use among women with type 2 diabetes mellitus (T2DM). METHODS: This study included women with T2DM, without a history of cancers, and followed up for more than one year from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) for the period 1998-2014. The dataset was structured using a person-time approach, where the cumulative medication usage was annually updated for each person. The extended Cox proportional hazards models were employed, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: During a median follow-up of 5 years, 515 of 29,498 women received a breast cancer diagnosis. Each additional year of metformin or statins use corresponded to a decrease in breast cancer incidence, while the magnitude attenuated over time. Noteworthily, statin use modified the effect of metformin on breast cancer incidence. For instance, after 5 years of follow-up, one-year increase of metformin use among women who used statins for 3 years was linked to a substantially reduced breast cancer risk (HR, 95% CI: 0.88, 0.84-0.93), however, there was no significant decrease in risk for those non-statins users (HR, 95% CI: 0.96, 0.89-1.04). CONCLUSIONS: Extending metformin or statin usage by one year conferred breast cancer protection in women with T2DM. Enhanced protective effect of metformin was observed among those who also use statins. These results suggest the potential of combined metformin and statin therapy as promising breast cancer prevention strategies.

Associated adverse health outcomes of polypharmacy and potentially inappropriate medications in community-dwelling older adults with diabetes.

Aim: This study aimed to identify the association of chronic polypharmacy and potentially inappropriate medications (PIMs) with adverse health outcomes (AHOs) in community-dwelling older adults with diabetes in China. Methods: A 2-year retrospective cohort study was conducted using 11,829 community-followed older adults with diabetes and medical records from 83 hospitals and 702 primary care centers in Shenzhen, China. Chronic polypharmacy and PIMs were identified from prescription records using Beers' criteria, and their associated AHO was analyzed using multivariable logistic regression analysis. Results: The prevalence of chronic polypharmacy and at least one PIM exposure was 46.37% and 55.09%, respectively. The top five PIMs were diuretics, benzodiazepines, first-generation antihistamines, sulfonylureas, and insulin (sliding scale). Chronic polypharmacy was positively associated with all-cause hospital admission, admission for coronary heart disease, admission for stroke, admission for dementia, and emergency department visits. Exposure to PIMs was positively associated with all-cause hospital admission, admission for heart failure (PIMs ≥2), admission for stroke (PIMs ≥3), emergency department visits, bone fracture, constipation, and diarrhea. Conclusion: Chronic polypharmacy and PIMs were prevalent in older adults with diabetes in Chinese communities. Iatrogenic exposure to chronic polypharmacy and PIMs is associated with a higher incidence of different AHOs. This observational evidence highlights the necessity of patient-centered medication reviews for chronic polypharmacy and PIMs use in older patients with diabetes in primary care facilities in China and draws attention to the caution of polypharmacy, especially PIM use in older adults with diabetes in clinical practice.

Molecular cloning, expression, and functional analysis of a putative lectin from the pearl oyster (Pinctada fucata, Gould 1850).

Marine lectins are a group of proteins that possess specific carbohydrate recognition and binding domains. They exhibit various activities, including antimicrobial, antitumor, antiviral, and immunomodulatory effects. In this study, a novel galectin-binding lectin gene named PFL-96 (GenBank: OQ561753.1) was cloned from Pinctada fucata. The PFL-96 gene has an open reading frame of 324 base pairs (bp) and encodes a protein comprising 107 amino acids. The protein has a molecular weight of 11.95 kDa and an isoelectric point of 9.27. It contains an N-terminal signal peptide and a galactose-binding lectin domain. The sequence identity to lectin proteins from fish, echinoderms, coelenterates, and shellfish ranges from 31.90 to 40.00 %. In the phylogenetic analysis, it was found that the PFL-96 protein is closely related to the lectin from Pteria penguin. The PFL-96 recombinant protein exhibited coagulation activity on 2 % rabbit red blood cells at a concentration of ≥8 µg/mL. Additionally, it showed significant hemolytic activity at a concentration of ≥32 µg/mL. The PFL-96 recombinant protein exhibited significant antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Candida albicans, and Vibrio alginolyticus, with minimum inhibitory concentrations (MIC) of 4, 8, 16, and 16 µg/mL, respectively. The minimum bactericidal concentrations (MBC) were determined to be 8, 16, 32, and 32 µg/mL, respectively. Furthermore, the PFL-96 recombinant protein exhibited inhibitory effects on the proliferation of Hela tumor cells, HepG2 tumor cells, and C666-1 tumor cells, with IC50 values of 7.962, 8.007, and 9.502 µg/mL, respectively. These findings suggest that the recombinant protein PFL-96 exhibits significant bioactivity in vitro, contributing to a better understanding of the active compounds found in P. fucata. The present study establishes a fundamental basis for further investigation into the mechanism of action and structural optimization of the recombinant protein PFL-96. The aim is to develop potential candidates for antibacterial and anti-tumor agents.

Elevated serum lead and cadmium levels associated with increased risk of dyslipidemia in children aged 6 to 9 years in Shenzhen, China.

Exposure to heavy metals can influence on metabolism, but studies have not fully evaluated young children. We investigated the association between levels of serum lead (Pb), cadmium (Cd), chromium (Cr), and arsenic (As) and risk of dyslipidemia in children. A total of 4513 children aged 6 to 9 years at 19 primary schools in Shenzhen were enrolled. Overall, 663 children with dyslipidemia were matched 1:1 with control by sex and age, and levels of serum Pb, Cd, Cr, and As were detected by inductively coupled plasma-mass spectrometry. Demographic characteristics and lifestyle were covariates in the logistic regression to determine the association of heavy metal levels with risk of dyslipidemia. Serum Pb and Cd levels were significantly higher in children with dyslipidemia than controls (133.08 vs. 84.19 µg/L; 0.45 vs. 0.29 µg/L; all P < 0.05), but this association was not found in Cr and As. We found significant upward trends for the odds ratios (ORs) of dyslipidemia associated with increasing quartiles of Pb and Cd levels (highest quartile of serum Pb OR 1.86, 95% confidence interval (CI) 1.46-2.38; Cd OR 2.51, 95% CI 1.94-3.24). Elevated serum Pb and Cd levels were associated with increased risk of dyslipidemia among children.

Role of Serum Lipids, Blood Glucose and Blood Pressure in Breast Cancer Risk for Women with Type 2 Diabetes Mellitus.

Purpose: Women with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer. We aimed to determine the contribution of lipids, glucose and blood pressure to this risk based on the multifactorial nature of T2DM. Patients and Methods: This population-based cohort study used data from a Dutch database (the Groningen Initiative to Analyse Type 2 Diabetes Treatment) for the period 2004-2013. The cohort included women diagnosed with T2DM, aged 30-80 years, with no history of breast cancer and with follow-up data for at least 1 year. We used Cox proportional hazards models to estimate the associations of exposures with breast cancer occurrence, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Exposures of interest included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glycated hemoglobin A (HbA1c) and systolic blood pressure (SBP). Results: During a median of 4.45 years' follow-up, 183 of 10,183 included women received a breast cancer diagnosis. We observed U-shaped associations with breast cancer incidence for total cholesterol and HDL-C at baseline. Compared with moderate elevations, women had significantly higher breast cancer risks associated with high total cholesterol (aHR, 95% CI: 1.72, 1.15-2.55) and HDL-C (aHR, 95% CI: 1.74, 1.18-2.58) levels, while low total cholesterol (aHR, 95% CI: 1.43, 0.94-2.19) and HDL-C (aHR, 95% CI: 1.44, 0.95-2.17) levels produced marginal effects without significance. Women with high LDL-C levels more often received a breast cancer diagnosis than those with medium levels (aHR, 95% CI: 1.56, 1.03-2.35). Conclusion: This real-world dataset highlights the importance of balancing lipid profiles, particularly total cholesterol and HDL-C. Dysregulation of the lipid profile, not the glucose or blood pressure profiles, may increase the risk of breast cancer in women with T2DM.

Prevalence of potentially inappropriate medications and association with comorbidities in older adults with diabetes in an outpatient visitation setting.

Aims: Potentially inappropriate medications had been found associated with adverse drug events such as falls, emergency department admissions and hospital readmissions. There is lack of information about the prevalence of potentially inappropriate medications and associated chronic conditions in older patients with diabetes in China. This study aimed to assess the prevalence of potentially inappropriate medications in older adults with diabetes in an outpatient visitation setting and the association with polypharmacy due to comorbidities. Materials and methods: This was a 3-year repeated cross-sectional study which conducted in outpatient setting of 52 hospitals in Shenzhen, China, using 2019 Beers criteria. The prevalence of potentially inappropriate medications, polypharmacy and comorbidities in older adults with diabetes in an outpatient setting was expressed as percentages. Logistic models were used to investigate the association between potentially inappropriate medication exposure and age, sex, polypharmacy and comorbidities. Results: Among the 28,484 older adults with diabetes in 2015, 31,757 in 2016 and 24,675 in 2017, the prevalence of potentially inappropriate medications was 43.2%, 44.88% and 42.40%, respectively. The top five potentially inappropriate medications were diuretics (20.56%), benzodiazepines (13.85%), androgens (13.18%), non-steroidal anti-inflammatory drugs (12.94%) and sulfonylureas (6.23%). After adjustment for age and polypharmacy, the probability of potentially inappropriate medication exposure was associated with chronic gastrointestinal diseases, followed by osteoarthritis and rheumatoid arthritis, chronic pulmonary disease, chronic kidney disease, tumor, dementia, chronic liver disease, hypertension, cardiovascular disease, cerebrovascular disease and hyperlipemia. Conclusion: Potentially inappropriate medications were common in older patients with diabetes in an outpatient visitation setting. Higher probability of potentially inappropriate medication exposure was associated with the comorbidity chronic gastrointestinal diseases as well as osteoarthritis and rheumatoid arthritis. To ensure that iatrogenic risks remain minimal for older adults with diabetes, the clinical comorbidities should be considered.

Effect of Exposure to Paternal Smoking on Overweight and Obesity in Children: Findings from the Children Lifeway Cohort in Shenzhen, Southern China.

INTRODUCTION: Paternal smoking associated with childhood overweight and obesity has been a concern, but studies have not investigated smoking exposure and smoking details. We investigated the association of exposures from paternal smoking as well as smoking details on offspring overweight/obesity. METHODS: A total of 4,513 children (aged 7-8 years) in Shenzhen were enrolled. Four different exposures from paternal smoking as well as smoking quantity, duration of smoking, and age of starting smoking details were the exposure variables and demographic characteristics, and circumstances of birth, dietary intake, lifestyle, and nonpaternal-smoking exposure were covariates in the logistic regression analysis to determine the effect of paternal smoking on childhood overweight/obesity, estimating odds ratios (ORs), and 95% confidence intervals (CIs). RESULTS: Paternal smoking was positively associated with childhood overweight/obesity (p < 0.05). Moreover, only preconception exposure, and both pre- and postconception exposure were significantly associated with childhood overweight/obesity (OR 1.54 [95% CI: 1.14-2.08] and OR 1.73 [95% CI: 1.14-2.61], respectively), restricted to boys but not girls. Furthermore, for children with only preconception paternal-smoking exposure, the dose-response relation was positive between smoking quantity, duration of smoking, age at starting, and overweight/obesity for boy offspring (p trend <0.001). We did not find any significant association between only postnatal exposure to paternal smoking and childhood overweight/obesity (p > 0.05). CONCLUSIONS: Our findings suggest that paternal smoking is associated with boys' overweight/obesity, and this association may be due to the paternal-smoking exposure before conception rather than the postnatal exposure to paternal smoking. Reducing paternal-smoking exposure before conception might help reduce overweight/obesity in boys.

The synergistic effect of Angelica sinensis (Oliv.) Diels and Rehmannia glutinosa (Gaertn.) DC. on antioxidant activity and protective ability against cell injury.

Oxidative stress-induced dysfunction of nerve cells has been implicated as a crucial cause of cell death in neurodegenerative diseases. In Asian countries, herbs, such as Angelica sinensis (Oliv.) Diels (DG) and Rehmannia glutinosa (Gaertn.) DC. (SDH), have long be considered to have antiaging abilities. The herbs act as neuro protectants that rescue nerve cells from oxidative stress damage and apoptosis. Thus, developing herbal formulas can potentially lead to new treatments for neurodegenerative diseases. In this study, we compared the effective active components and antioxidant properties of extractive of DG and SDH (DG-SDH) when formulated at different ratios. DG-SDH formulated at a ratio of 3:2 (DG-SDH [3:2]) produced the highest content of polysaccharides, polyphenols, and flavonoids. It also showed the best ability in removing DPPH and hydroxyl free radicals compared to single herb or other compounding ratio. The antioxidant activity of DG-SDH (3:2) showed best synergistic effects in scavenging activity assays of DPPH free radicals and hydroxyl free radicals. DG-SDH (3:2) could increase the cell viability of SHSY-5Y cells, PC-12 cells, and BV-2 cells. In particular, DG-SDH (3:2) protected SHSY-5Y cells from H2 O2 -induced cell injury by inhibiting excessive expression of reactive oxygen species (ROS), reducing the rate of apoptosis and restoring mitochondrial membrane potential. Actin-Tracker Green and DAPI staining and fluorescence microscope observation confirmed that DG-SDH (3:2) helped in preserving cell morphology under oxidative stress. These findings support that DG-SDH (3:2) promote the neuroprotection against hydrogen peroxide and can serve as a novel therapy for neurodegenerative diseases. PRACTICAL APPLICATIONS: This is the first study to investigate DG and SDH interaction between effective ingredients. These findings support that DG-SDH (3:2) has the best synergistic effects in antioxidant activity and promote the neuroprotection against hydrogen peroxide. Hence, DG-SDH (3:2) will be an excellent candidate to be developed as a functional food ingredients or nutraceuticals for neurodegenerative diseases.

[Quality standard of Lobeliae Chinensis Herba].

In light of related methods in Chinese Pharmacopoeia(2020 edition), this study established the quality standard for Lobeliae Chinensis Herba. The TLC identification method was established with silica gel GF_(254) thin layer plate, diosmin standard, linarin standard, and the reference material of Lobeliae Chinensis Herba. The loss on drying, total ash, acid-insoluble ash, and ethanol-soluble extracts of 18 batches of Lobeliae Chinensis Herba samples were determined according to the general principles in Chinese Pharmacopoeia. Then, HPLC was adopted in the establishment of characteristic chromatogram and content determination. The results showed that the established method can achieve good separation for diosmin, linarin, and lobetyolin. Based on the results of detection for 18 batches of Lobeliae Chinensis Herba samples, the draft quality standard was established, which was expected to provide reference for the revision of this medicinal herb in Chinese Pharmacopoeia.

Type 2 Diabetes Mellitus and Clinicopathological Tumor Characteristics in Women Diagnosed with Breast Cancer: A Systematic Review and Meta-Analysis.

Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by using a random effects model. T2DM was significantly associated with tumor stages III/IV versus cancers in situ and stages I/II (pooled ORs (pOR), 95% CI: 1.19; 1.04-1.36, p = 0.012), tumor size >20 versus ≤20 mm (pOR, 95% CI: 1.18; 1.04-1.35, p = 0.013), and lymph node invasion versus no involvement (pOR, 95% CI: 1.26; 1.05-1.51, p = 0.013). These findings suggest that women with T2DM are at a higher risk of late-stage tumors, large tumor sizes, and invasive lymph nodes at breast cancer diagnosis.

Impact of early life exposures on COPD in adulthood: A systematic review and meta-analysis.

Early life represents a critical period for the development and growth of the lungs. Adverse exposures in this stage may drive the development of chronic obstructive pulmonary disease (COPD). Thus, we quantitatively evaluated the impact of different early life exposures on COPD in adulthood. The PubMed, Embase and Cochrane Library electronic databases were searched for articles published from January 2001 to October 2020. A total of 30 studies (795,935 participants) met the criteria and were included in the review. We found a significant association of COPD with childhood serious respiratory infections, pneumonia or bronchitis (pooled adjusted OR [aOR], 2.23 [95% CI, 1.63-3.07]). The probability of COPD was increased 3.45-fold for children with than without asthma (pooled aOR, 3.45 [95% CI, 2.37-5.02]). In addition, the probability of COPD was associated with maternal smoking (pooled aOR, 1.42 [95% CI, 1.17-1.72]), any child maltreatment (pooled aOR, 1.30 [95% CI, 1.18-1.42]) and low birth weight (pooled aOR, 1.58 [95% CI, 1.08-2.32]) but not childhood environmental tobacco smoke exposure (pooled aOR, 1.15 [0.83-1.61]) or premature birth (pooled aOR, 1.17 [95% CI, 0.87-1.58]). Furthermore, subgroup analyses revealed that probability was increased for only women with childhood physical abuse, sexual abuse and exposure to intimate partner violence. Factors resulting in COPD in adults could trace back to early life. Childhood respiratory disease, maltreatment, maternal smoking and low birth weight increase the risk of COPD. Promising advances in prevention strategies for early life exposures could markedly decrease the risk of COPD.

Oleanane-type saponins and prosapogenins from Albizia julibrissin and their cytotoxic activities.

Two undescribed oleanane-type saponins, julibrosides K-L, along with three undescribed oleanane-type prosapogenins, julibrosides M-O, were isolated from the stem bark of Albizia julibrissin Durazz. and the mild alkaline hydrolysate of the total saponin, respectively. Their structures were established by extensive analysis of 1D and 2D NMR experiments (COSY, TOCSY, HSQC, HMBC, and HSQC-TOCSY) and mass spectrometry. Furthermore, the cytotoxic activities of the isolated compounds against BGC-823, A549, HCT-116, and HepG2 cell lines were evaluated, and julibroside L showed significant cytotoxic activities against the four cancer cell lines with IC50 values of 5.77, 4.80, 4.26, and 4.93 µM, respectively.

Anthropometry did not approach adequate predictive accuracies for detecting elevated fasting plasma glucose or hemoglobin A1c levels among Chinese children aged 7-9 years.

AIMS/INTRODUCTION: Elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) are well-established independent risk factors for progression to diabetes, cardiovascular comorbidities and mortality. Most previous studies on the relationships of anthropometric measures with hyperglycemia were carried out among adults and adolescents, but few data are available for the performance predication of the predictors for diagnosing elevated FPG or HbA1c among young children. MATERIALS AND METHODS: Involving 5,556 students of aged 7-9 years, a school-based cross-sectional survey was carried out between March and June 2019 in Shenzhen, China. Receiver operating characteristic curve analysis was utilized. RESULTS: The median was 4.6 (interquartile range [IQR] 4.3-4.8) mmol/L for FPG and 5.3% (IQR 5.1-5.5%) for HbA1c levels for all participants. For detecting elevated FPG, weight (0.651, IQR 0.583-0.719) and waist circumference (0.650, IQR 0.584-0.717) showed the highest area under the curve and 95% confidence interval, followed by body mass index and the z-score of body mass index (both 0.635, IQR 0.567-0.703); other anthropometric measures showed poorer diagnostic efficiencies or no ability. For detecting elevated HbA1c, lower efficiencies for the Conicity Index (0.651, IQR 0.583-0.719), waist-to-height ratio, waist-to-hip ratio and waist-to-chest ratio were shown. The correlations of FPG and HbA1c levels with anthropometric indices were weak (Spearman's r ≤ 0.179). CONCLUSIONS: None of the evaluated anthropometric indicators approached an adequate predictive accuracy for the detection of elevated FPG or HbA1c levels in Shenzhen children aged 7-9 years. The current study did not recommend anthropometry screening for prediabetes in young children.

(+)- and (-)-Corydecumbenines A and B, two pairs of novel quaternary protoberberine alkaloid cycloadduct enantiomers with anti-neuroinflammatory and neuroprotective activities from the rhizomes of Corydalis decumbens.

Two novel Diels-Alder [4 + 2] cycloadducts of quaternary protoberberine alkaloids and fumaric acid monoanion, corydecumbenines A and B (1 and 2), and six known isoquinoline analogues (3-8) were isolated from the rhizomes of Corydalis decumbens. The planar structures of 1 and 2 were elucidated by extensive spectroscopic analysis including UV, IR, HRESIMS, 1D and 2D NMR. Chiral chromatography of 1 and 2 afforded two pairs of enantiomers (+)-corydecumbenine A (1a), (-)-corydecumbenine A (1b), (+)-corydecumbenine B (2a), and (-)-corydecumbenine B (2b), respectively, and their absolute configurations were determined by single-crystal X-ray crystallography and comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1b and 2b exhibited significant nitric oxide (NO) inhibitory activities in lipopolysaccharide (LPS)-stimulated BV-2 cells with IC50 values of 11.6 and 16.2 µM, respectively, comparable to the positive control indomethacin (IC50 = 10.3 µM), and they could also decrease the level of interleukin (IL)-1ß in BV-2 cells in a dose-dependent manner. Most of the isolates showed neuroprotective effects against the injury of OGD/R-induced PC12 cells at 20 µM.

The effectiveness of cupping therapy on chronic fatigue syndrome: A single-blind randomized controlled trial.

BACKGROUND: and purpose: We investigated the effectiveness of cupping therapy with three different pressures in patients with chronic fatigue syndrome (CFS). MATERIALS AND METHODS: The participants were randomly assigned to three groups, as follows: cupping pressure of -0.02 mpa (n = 38), -0.03 mpa (n = 38), or -0.05 mpa (n = 36). Each group received cupping treatment that consisted of 10 sessions over 5 weeks (2 sessions per week). The primary outcomes were Fatigue Scale (FS-14) score and Fatigue Assessment Instrument (FAI) score after 5 and 10 sessions. The secondary outcomes were the Self-Rating Anxiety Scale (SAS) score, the Self-Rating Depression Scale (SDS) score, and the Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: There were 91 participants who completed the trial. After five sessions of treatment, the primary outcome of FS-14 score decreased by 3.20 (2.19, 4.21) in the -0.02 mpa group, by 2.39 (1.51, 3.27) in the -0.03 mpa group, and by 3.40 (2.28, 4.52) in the -0.05 mpa group (P = 0.667). After 10 sessions of treatment, the outcome of FS-14 score decreased by 5.00 (3.79, 6.21) in the -0.02 mpa group, by 4.06 (3.07, 5.05) in the -0.03 mpa group, and by 4.77 (3.52, 5.94) in the -0.05 mpa group (P = 0.929). And, the results were statistically different between 5 sessions and 10 sessions of treatment (P < 0.01). However, there were no statistical differences in FAI, SAS, SDS, and PSQI scores between the three groups after 5 sessions and 10 sessions of treatment. CONCLUSIONS: In conclusion, cupping therapy has significantly relieved fatigue symptoms and improved emotion and sleep condition of CFS patients, and 10 sessions of treatment had superior results compared with 5 sessions in each group. Moreover, in 5 sessions of treatment, cupping with high pressure showed better improvement in fatigue syndromes and sleep condition according to effective rates. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR1800017590); Ethical approval number: ChiECRCT-20180085.

Alisol A is potentially therapeutic in human breast cancer cells.

Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA­MB­231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24­acetate, alisol B and alisol B 23­acetate. Among these, alisol A significantly inhibited cell viability. Alisol A induced cell apoptosis, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA­MB­231 cells. The number of APE1­/γH2AX­/LC3­II positive cells was also significantly higher compared with that of negative control cells. All these results were dose­dependent. Cleaved caspase­3, cleaved caspase 9, Bcl­2, and p­p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3­II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy­dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.

Anti-inflammatory quinoline alkaloids from the root bark of Dictamnus dasycarpus.

Six undescribed quinoline alkaloids, named dasycarines A-E, and 18 known ones were isolated from the root bark of Dictamnus dasycarpus. All the structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, and HRMS spectroscopic data, and the absolute configurations were assigned via comparison of the calculated and experimental ECD data. (+)-Dasycarine A (1a) and (-)-Dasycarine A (1b) are a pair of enantiomers of dimeric furoquinoline alkaloid, which are the first dimeric via [2 + 2] cycloaddition of furan. The structure and absolute configuration of (-)-dasycarine A was determined via X-ray crystallography. Additionally, all the isolated compounds were tested for their inhibitory effects on NO production stimulated by LPS in BV-2 microglial cells. Three compounds showed strong inhibition with IC50 values below 5.0 µM; nine compounds exhibited inhibition with IC50 values in the range of 7.8-28.4 µM. Furthermore, we demonstrated that preskimmianine suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB) in LPS-induced BV-2 microglial cells.

Ambient air pollution and markers of fetal growth: A retrospective population-based cohort study of 2.57 million term singleton births in China.

BACKGROUNDS: Evidence is scarce on the relation between maternal exposure to ambient air pollution during pregnancy and fetal growth in developing countries. Moreover, the current evidence is inconsistent. We aimed to investigate the association of trimester-specific exposure to air pollution with risk of being born small for gestational age (SGA) and birth weight-markers of fetal growth-among Chinese term births. METHODS: This retrospective population-based cohort study consisted of 2,567,457 singleton term live-births from January 1, 2014 to December 31, 2017 across 123 Chinese districts and counties. Personal exposure to ambient air pollutants including carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), particulate matter with aerodynamic diameter < 2.5 µm (PM2.5), and PM10 was assigned using the inverse distance weighting spatial interpolation algorithm. Generalized estimating equations (GEE) logistic regression models were performed to estimate the associations between trimester-specific exposure to air pollution and risk of SGA or low birth weight (LBW), and GEE linear regression to examine the associations between the exposure and term birth weight, adjusting for maternal demographics, maternal cigarette smoking status during pregnancy, mode of delivery, gravidity, gestational age, year and month of conception, neonate's sex, and meteorological factors. Stratified and sensitivity analyses were also performed. RESULTS: When mother exposed to ambient air pollutants over the entire pregnancy, per IQR increment (0.122 mg/m3) in ambient CO concentrations was associated with higher risk of SGA (odds ratio (OR) = 1.04, 95% confidence interval (CI): 1.02, 1.05) and reduced birth weight among term births (-5.95 g, 95% CI: -8.01, -3.89). This association was also pronounced in the second and third trimesters. Term birth weight was negatively associated with per IQR increase of O3 (-3.52 g, 95% CI: -6.23, -0.81), PM2.5 (-5.93 g, 95% CI: -8.36, -3.49) and PM10 (-7.78 g, 95% CI: -10.41, -5.16) during the entire pregnancy, respectively. No significant association was detected between maternal exposure to air pollutants and term LBW. Effect estimates of heterogeneity suggested that maternal age and infant sex modified the impact of air pollution on birth weight. CONCLUSIONS: The findings suggest that maternal exposure to air pollution during pregnancy is adversely affecting fetal growth. Further studies are warranted to integrate these findings and take clinical or public health interventions in pregnancy.

Glucoconjugated Monoterpene Indole Alkaloids from Uncaria rhynchophylla.

Twenty-six glucoconjugated monoterpene indole alkaloids, including 12 new compounds, rhynchophyllosides A-L (1-12), and 14 known ones, 13-26, were obtained from the hook-bearing stems of Uncaria rhynchophylla (Miq.) Miq. ex Havil. Their structures were unambiguously elucidated by analyses of UV, MS, NMR, ECD, and single-crystal X-ray diffraction data. The ESI-MSn behavior of the new glucoalkaloids was also elucidated. Although comprising the same glucosyl moiety, the aglycone skeletons and glucosidic numbers and linkage varied greatly, implying the diversity in biosynthetic pathways. This is the first report of such structurally diverse glucoconjugated monoterpene indole alkaloids from U. rhynchophylla. Compound 1 represents a new subtype of oxindole alkaloid with a seven-membered D-ring, 10 is a rare monoterpene indole alkaloid with the glucosyl moiety located at C-9, 4 and 5 are the first two oxindole alkaloid diglycosides, and 11 and 12 represent the first two examples of alkaloids with a quinolone nucleus from the genus Uncaria. Compound 10 exhibited moderate acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 10.5 µM. Molecular docking was performed to explore the binding mode of inhibitor 10 at the active site of AChE.

Overexpression Of hsa-miR-664a-3p Is Associated With Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Via Targeting FHL1.

Background: Chronic obstructive pulmonary disease (COPD) is recognized as a chronic lung disease with incomplete reversible airflow limitation, but its pathophysiology was still not clear. This study aimed at investigating regulatory roles of special miRNA-mRNA axis in COPD development. Methods: Differentially expressed miRNAs and downstream mRNAs were screened from the Gene Expression Omnibus (GEO) dataset by using the LIMMA package in R software. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct a co-expression network for COPD. The correlation of dysregulated miRNA(s) and COPD was analyzed, and miRNAs with significant differences were validated in peripheral blood mononuclear cells (PBMCs) from COPD patients by real-time PCR. Regulatory roles of candidate miRNAs and targeted mRNAs were investigated in vitro study. Results: Thirteen modules of co-expressed miRNAs and mRNAs were constructed from a selected cohort with WGCNA. Turquoise module with 12 differentially expressed miRNAs and 120 mRNAs was significantly correlated with COPD. The expression of hsa-miR-664a-3p, an upregulated miRNA in the module, was increased both in lung tissue and PBMCs from COPD patients, whereas that targeted four and a half LIM domains 1 (FHL1) gene was decreased and positively correlated with forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC%) (r = 0.59, p < 0.01). In vitro, luciferase activity assay revealed FHL1 as a target of hsa-miR-664a-3p and it could be directly downregulated by overexpression of hsa-miR-664a-3p. Furthermore, cigarette smoke extract could increase hsa-miR-664a-3p level and decrease FHL1 level in Beas-2B cells. Conclusion: The present study validated significant upregulation of hsa-miR-664a-3p in COPD patients, and its target gene FHL1 was downregulated and positively correlated with FEV1/FVC%; both hsa-miR-664a-3p and FHL1 could be regulated by cigarette smoke extract. Results of bioinformatic analyses and expanded validation suggest that the axis from hsa-miR-664a-3p to FHL1 might play a key role in cigarette smoke-induced COPD, and the exact mechanism should be confirmed in further studies.