Acute vaping exacerbates microbial pneumonia due to calcium (Ca2+) dysregulation.

As electronic cigarette (E-cig) use, also known as "vaping", has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel syndrome based on single-cell sequencing technology.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

Efficacy and safety of Huaier granules combined with chemotherapy for gastric cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Huaier granules, the aqueous product of Huaier (Trametes robiniophila Murr.) extract, are a broad-spectrum anti-tumor drug and have been widely used for the treatment of gastric cancer (GC). The aim of this study is to systematically investigate the efficacy and safety of Huaier granules combined with chemotherapy in the treatment of GC. METHODS: Three English databases and four Chinese databases will be searched from its inception to July 2020. Two methodological trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.2 and stata 14.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Huaier granules combined with chemotherapy is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/9BVJD.

Traditional Chinese biomedical preparation (Huaier Granule) for breast cancer: a PRISMA-compliant meta-analysis.

Huaier Granule, a type of traditional Chinese biomedical preparation (TCBP), is considered to be a promising adjuvant therapy for breast cancer. Although an analysis of the published literature has been performed, the exact effects and safety of Huaier Granule remains controversial. Therefore, a wide-ranging systematic search of electronic databases from which to draw conclusions was performed. Data from 27 trials, including 2562 patients with breast cancer were analyzed. The results indicated that, compared with conventional treatment alone, the combination of conventional treatment and Huaier Granule markedly improved patients' overall response (P=0.02) and quality of life (P<0.00001), and significantly prolonged 2-year (P=0.02), 3-year (P<0.0001) and 5-year (P=0.004) overall survival rates, and 1-year (P=0.003), 2-year (P<0.00001), 3-year (P<0.00001) and 5-year (P=0.03) disease-free survival. The immune function of patients was also significantly enhanced after combined intervention treatment, indicated by clearly increased percentages of CD3+ (P=0.05), CD4+ (P<0.00001) and natural killer cells (P<0.0001), and CD4+/CD8+ ratio (P<0.00001). The incidence of myelosuppression (P=0.001) and hepatotoxicity (P=0.05) was lower in breast cancer patients treated with Huaier Granule, whereas other adverse events did not differ significantly between the two groups (P>0.05). In summary, results of this meta-analysis suggest that the combination of conventional treatment and Huaier Granule is more effective for the treatment of breast cancer than conventional treatment alone.

Trametes robiniophila Murr in the treatment of breast cancer.

Breast cancer is the leading cause of cancer death among women across the world. Trametes robiniophila Murr (Huaier), a traditional herbal medicine, has been used in China to protect human health for about 1600 years. Recent years, Huaier had been proven to be effective for multiple types of malignancies. This systematic review focused on breast cancer treatment, summarizing the curative function of Huaier aqueous extract and polysaccharides in preclinical researches. Huaier could markedly inhibit breast cancer progression with low toxicity, enhance immune response and increase the sensitivity to radiation and chemotherapy. The therapeutic effect of Huaier granule in clinical studies was also included. This review amalgamated the current studies and highlighted the promising role of Huaier and its polysaccharides as complementary alternative medicine in breast cancer treatment.

A Quantile-Based g-Computation Approach to Addressing the Effects of Exposure Mixtures.

BACKGROUND: Exposure mixtures frequently occur in data across many domains, particularly in the fields of environmental and nutritional epidemiology. Various strategies have arisen to answer questions about exposure mixtures, including methods such as weighted quantile sum (WQS) regression that estimate a joint effect of the mixture components. OBJECTIVES: We demonstrate a new approach to estimating the joint effects of a mixture: quantile g-computation. This approach combines the inferential simplicity of WQS regression with the flexibility of g-computation, a method of causal effect estimation. We use simulations to examine whether quantile g-computation and WQS regression can accurately and precisely estimate the effects of mixtures in a variety of common scenarios. METHODS: We examine the bias, confidence interval (CI) coverage, and bias-variance tradeoff of quantile g-computation and WQS regression and how these quantities are impacted by the presence of noncausal exposures, exposure correlation, unmeasured confounding, and nonlinearity of exposure effects. RESULTS: Quantile g-computation, unlike WQS regression, allows inference on mixture effects that is unbiased with appropriate CI coverage at sample sizes typically encountered in epidemiologic studies and when the assumptions of WQS regression are not met. Further, WQS regression can magnify bias from unmeasured confounding that might occur if important components of the mixture are omitted from the analysis. DISCUSSION: Unlike inferential approaches that examine the effects of individual exposures while holding other exposures constant, methods like quantile g-computation that can estimate the effect of a mixture are essential for understanding the effects of potential public health actions that act on exposure sources. Our approach may serve to help bridge gaps between epidemiologic analysis and interventions such as regulations on industrial emissions or mining processes, dietary changes, or consumer behavioral changes that act on multiple exposures simultaneously. https://doi.org/10.1289/EHP5838.

Quercetin Attenuates Acute Lung Injury Caused by Cigarette Smoke Both In Vitro and In Vivo.

Cigarette smoke is highly toxic and is a major risk factor for airway inflammation, oxidative stress, and decline in lung function-the starting points for chronic obstructive pulmonary disease. Quercetin is a potent dietary antioxidant that displays anti-inflammatory activities. The goal of this study was to evaluate the effects of quercetin on reducing the redox imbalance and inflammation induced by short-term cigarette smoke exposure. In vitro, 25 and 50 µM quercetin attenuated the effects of cigarette smoke extract (increased generation of reactive oxygen species and nitric oxide) on J774A.1 cells (macrophages). We further examined the effects of quercetin in vivo. Male C57Bl/6 mice that received 10 mg/kg/day of quercetin via orogastric gavage before exposure to five days of cigarette smoke demonstrated reduced levels of leukocyte, oxidative stress, histological pattern changes of pulmonary parenchyma, and lung function alterations compared to the group that did not receive quercetin. These results suggest that quercetin may be an effective adjuvant for treating the effects of cigarette smoke exposure.

Factors affecting the outcome of endoscopic dilatation in refractory post-corrosive oesophageal stricture in Egyptian children: a single-centre study.

BACKGROUND: An important complication of corrosive ingestion is oesophageal stricture. Improvements in endoscopes and accessories have supported an increase in the number of patients who are conservatively treated with endoscopic dilations. In this study, we aimed to detect factors affecting the outcome of endoscopic dilatation for refractory post-corrosive oesophageal stricture. METHODS: This study was carried out in the Paediatric Endoscopy Unit in the Children's Hospital and included 100 children older than 2 years of age of both sexes who had an established diagnosis of post-corrosive oesophageal stricture on repeated endoscopic dilatation sessions. The duration of the condition was more than 6 months, and dilatation failed to achieve a diameter of 14 mm during the first five sessions at 2-week intervals (refractory), excluding other causes of oesophageal stricture. RESULTS: Males represented 63% of patients. The mean age of enrolled children was 5.9 ± 2.6 years; 90% of patients ingested an alkaline corrosive substance (potash). The total number of dilatation sessions ranged from 16 to 100, with a mean number of sessions ranging from 37.2 ± 14.9. Fifty-four patients (54%) were well controlled by regular endoscopic dilatation with good clinical and endoscopic outcomes, and no more dilatations were needed. CONCLUSION: Endoscopic dilation is an effective method for managing refractory post-corrosive oesophageal strictures that require a long follow-up period. There are a lot of factors affecting the outcome.

Target lipidomics approach to reveal the resolution of inflammation induced by Chinese medicine combination in Liu-Shen-Wan against realgar overexposure to rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Liu-Shen-Wan (LSW) is one of the popular over-the-counter drugs in Asia, which contains realgar (As4S4), used for the treatment of upper respiratory tract inflammation and skin infections. However, the safety and potential risk of this arsenic remain unknown. AIM OF THE STUDY: The aim of this study was to determine total arsenic in tissue and investigate effects of regular dose and overdose LSW exposure on rat liver. MATERIALS AND METHODS: We used a target lipidomics approach to quantify inflammatory eicosanoids and employed ICP-MS to determine total arsenic in tissue. RESULTS: The results showed that oral administration of 8 and 40 mg/kg LSW (1 and 5 fold human-equivalent dose) induced light changes of liver lipidomic profile in rats, which was associated with anti-inflammatory function of LSW. In our recent report, we observed that 41 and 134 mg/kg realgar (40 and 132 fold human-equivalent dose) stimulated rat liver inflammation through up-regulation of pro-inflammatory LOX-derived, CYP-derived HETEs and COX-derived PGs. However, we found that LSW in the form of drug combination, containing 41 and 134 mg/kg realger, could not stimulate these similar inflammatory responses in rats, although the liver total arsenic levels of the realger and LSW groups were same. CONCLUSION: The downregulation of pro-inflammatory response showed that the LSW containing realger is safer than realger alone administrated to rats. These results suggested that Chinese medicines combination could reduce realgar-derived arsenic toxicity in rats.

Ethnopharmacological activity of Hedera nepalensis K. Koch extracts and lupeol against alloxan-induced type I diabetes

In this study, we investigated the protective effects of Hedera nepalensis crude extract, its fractions and lupeol in alloxan-induced diabetic rats. Lupeol and n-hexane (HNN) fraction significantly reduced the blood glucose level by increasing insulin level in time dependent manner, and also significantly increased amylase and lipase activity in diabetic rats. Elevated levels of alanine transaminases (ALT), aspartate transaminases (AST), thiobarbituric acid reactive substances (TBARS), nitrite, hydrogen peroxide (H2O2), total bilirubin and total protein in blood serum were efficiently restored to normal levels. Suppressed enzymatic activity of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and peroxidase (POD) were also restored to their normal levels. Kidney functions were also restored to normal level after treatment with HNN and lupeol. HNN fraction and lupeol of H. nepalensis prevented oxidative stress in alloxan-induced diabetic rats. This study signifies the importance of H. nepalensis and lupeol in ameliorating diabetes by inducing insulin secretion in diabetic model rats.

Complex contaminant mixtures and their associations with intima-media thickness.

BACKGROUND: The burden of cardiovascular disease (CVD) morbidity and mortality is higher among Indigenous persons, who also experience greater health disparities when compared to non-Indigenous Canadians, particularly in remote regions of Canada. Assessment of carotid intima-media thickness (cIMT), a noninvasive screening tool and can be used as biomarker to assess increased CVD risk. Few studies have examined environmental contaminant body burden and its association with cIMT. METHODS: Data from the Environment-and-Health Study in the Eeyou Istchee territory of northern Québec, Canada was used to assess complex body burden mixtures of POPs, metals and metalloids among (n = 535) Indigenous people between 15 and 87 years of age with cIMT. First, Principal Component Analysis (PCA) was used to reduce the complexity of the contaminant data. Second, based on the underlying PCA profiles from the biological data, we examined each of the prominent principal component (PC) axes on cIMT using multivariable linear regression models. Lastly, based on these PC axes, cIMT was also regressed on summed (Σ) organic compound concentrations, polychlorinated biphenyl, perfluorinated compounds, respectively, ∑10 OCs, ∑13 PCBs, ∑3PFCs, and nickel. RESULTS: Most organochlorines and PFCs loaded primarily on PC-1 (53% variation). Nickel, selenium, and cadmium were found to load on PC-5. Carotid-IMT was significantly associated with PC-1 ß = 0.004 (95 % CI 0.001, 0.007), and PC-5 ß = 0.013 (95 % CI 0.002, 0.023). However, the association appears to be greater for PC-5, accounting for 3% of the variation, and mostly represented by nickel. Results show that that both nickel, and ∑3PFCs were similarly associated with cIMT ß = 0.001 (95 % CI 0.0003, 0.003), and ß = 0.001 (95 % CI 0.0004, 0.002), respectively. But ∑10OCs was significantly associated with a slightly greater ß = 0.004 (95 % CI 0.001, 0.007) cIMT change, though with less precision. Lastly, ∑13PCBs also increased ß = 0.002 (95 % CI 0.0004, 0.003) cIMT after fully adjusting for covariates. CONCLUSION: Our results suggest that environmental contaminants are associated with cIMT. This is important for the Cree from the Eeyou Istchee territory who may experience higher body burdens of contaminants than non-Indigenous Canadians.

Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial.

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.

Preventive effect of purgative manna on neonatal jaundice: A double blind randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Cotoneaster nummularioides Pojark manna (Shir-e-Khesht) is popular in Persian medicine. Different effects of some Cotoneaster species manna include antibacterial, antioxidant, anticancer, and hepatoprotective effects, as well as bilirubin serum levels reduction. Cotoneaster species manna is used in many parts of Iran as a laxative and accelerates the passage of meconium. Neonatal jaundice has relatively costly and sometimes invasive therapeutic interventions, which its prevention from becoming severe cases can be a priority in neonatal medicine. AIM OF THE STUDY: The aim of this study was to evaluate the effectiveness of an herbal product (Purgative Manna, native to Iran and Asian countries) in preventing severe cases of jaundice and reducing total bilirubin levels in neonates. MATERIALS AND METHODS: This randomized double-blind controlled clinical trial included full-term babies. Four hundred and forty-five (445) eligible neonates were assigned to two groups using the block balanced randomization method; 222 neonates received the Purgative Manna product as drops, and 223 neonates received placebo drops. The neonates received a dose of 5 drops per kilogram of neonatal weight (divided into three doses per day) for three days. The treatment period was three days, and a 24-h (three times) examination was performed to measure the initial outcome of the trial (i.e., the total serum bilirubin level). The secondary outcomes of this trial were the need for hospitalization due to jaundice and/or phototherapy from 4 to 14 days after birth, the frequency of defecation within 24 h, and the triple complications of diarrhoea, dehydration symptoms, and abdominal colic. RESULTS: In this study, 220 neonates in the Purgative Manna product group and 222 neonates in the placebo group completed their interventions within the predicted period of the study. At the end of study, the total bilirubin level in the Purgative Manna treated group was significantly lower than that of the placebo group. The difference between the mean total bilirubin levels of the two groups was approximately 2.1 mg/dl on the third day after treatment, with an effect size of 0.79 (95% CI: 0.06-0.98). The relative risk for reducing the need for hospitalization or phototherapy in the group treated with Purgative Manna drops was 0.26, compared with the placebo group. The risk of occurrence of severe jaundice or phototherapy in the Purgative Manna group was 75% lower than that of the placebo group. The median frequency of defecation in the intervention group at three time intervals in the first, second and third days after treatment was 1-2 times more than that of the comparison group (p < 0.001). CONCLUSIONS: Meanwhile, considering the fact that one in every eight neonates who used the product avoided having a severe and high-risk case of jaundice or the need for phototherapy intervention (even through an exchange transfusion), the use of Purgative Manna drops can be recommended; however, further study is necessary.

Effects of Exposure to Carbon Dioxide in Potash Miners.

Potash miners can become exposed to carbon dioxide (CO2) during the blasting of basalt intrusions or loading and transporting the blasted salt. In a cross-shift study, we compared physiological effects of acute exposure to elevated CO2 concentrations in miners after long-term exposure to evaluate the possible health risks. A group of 119 miners was assessed by clinical examination, lung function tests, and blood gas content directly before and after the shift. A cumulative CO2 exposure was measured using personal monitors. The miners were categorized as low (<0.1 vol.%, n = 83), medium (<0.5 vol.%, n = 26), and high (>0.5 vol.%, n = 10) CO2 exposed subjects. We found no significant differences among the three groups. Lung function testing revealed no conspicuous findings, and chronic health effects were not observed in the miners either. In conclusion, no significant adverse effects could be found in potash miners exposed to elevated CO2 concentrations. Therefore, the mining authorities allow potash mining operations for 4 h at ambient CO2 up to 1.0 vol.% and for 2 h at CO2 not exceeding 1.5 vol.% per shift.

Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.

OBJECTIVE: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function. METHODS: AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed. RESULTS: Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function. CONCLUSIONS: ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.

Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial.

OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.

Exposure to Mixtures of Pollutants in Mexican Children from Marginalized Urban Areas.

BACKGROUND: Exposure to contaminant mixtures in developing countries is an important public health issue. Children are identified as the most susceptible group to adverse health effects due to the exposure. OBJECTIVE: The aim of this study was to conduct a screening for mixture pollutants in Mexican children in urban marginalized communities. METHODS: We analyzed children (aged 6-12 years old) who resided in four urban marginalized communities in San Luis Potosi, Mexico: i) Bellas Lomas (BEL), a site with vehicular traffic; ii) Tercera Chica (TC), a site with brick kilns; Iii) Rincon de San Jose (SJR), a site with a hazardous waste landfill; and (iv) Morales (MOR) a metallurgical zone with copper-arsenic and electrolytic zinc smelters. Polycyclic Aromatic Hydrocarbons (1-hydroxypyrene (1-OHP)), benzene (trans, trans-muconic acid (t,t-MA), manganese, arsenic and fluoride were quantified in urine and lead in blood samples. FINDINGS: Our results indicate that median exposures to manganese were 4.4, 5.2, 5.8 and 6.3 µg/L for BEL, TC, SJR and MOR, respectively. For BEL, fluoride was present at a higher concentration with 2.3 mg/L followed by MOR, TC and SJR with 1.7, 1.5 and 1.2 mg/L respectively. The highest concentrations of arsenic that were found were 11 µg/L in MOR and lead concentration was reported between 4.2 and 6.8 µg/dL, in BEL, TC and MOR. 1-OHP and t,t-MA were higher in TC (0.23 µmol/mol creatinine (cr), 429.7 µg/g cr, respectively) followed by SJR (0.09 µmol/mol cr, 427.4 µg/g cr), MOR (0.03 µmol/mol cr, 258.6 µg/g cr) and BEL (0.06 µmol/mol cr, 220.6 µg/g cr). CONCLUSION: Considering the large number of people, especially children, exposed to multiple pollutants, it is important to design effective intervention programs that reduce exposure and the resultant risk in the numerous urban marginalized communities in Mexico.

Carcinogenicity of smokeless tobacco: Evidence from studies in humans & experimental animals.

A Working Group of the Monographs programme of the International Agency for Research on Cancer has classified smokeless tobacco as carcinogenic to humans (Group 1). This review article summarizes the data that support the evaluations of sufficient evidence in humans and in experimental animals for the carcinogenicity of smokeless tobacco whether used alone or with betel quid. It also identifies compounds of smokeless tobacco relevant to carcinogenicity (prominently tobacco-specific nitrosamines) and addiction (nicotine). The epidemiological evidence is summarized for oral cancer, other cancers associated with smokeless tobacco and oral potentially malignant lesions with a focus on analytical studies from the SEARO Region. Studies on cancer in experimental animals are summarized with a focus on studies applying smokeless tobacco products typical for the regions, such as mishri and naswar.

An obesogenic diet enriched with blue mussels protects against weight gain and lowers cholesterol levels in C57BL/6 mice.

Obesity is linked to several health complications, such as cardiovascular disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of the prime causes for health complications. We have previously shown that blue mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA) and increase the mRNA expression of peroxisome-proliferator activated receptor and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in vitro. However, the in vivo effects of BM on obesity and metabolic regulation are not known. We hypothesized that dietary intake of BM will prevent weight gain and improve lipid profile of C57BL/6 mice fed a high-fat diet (HFD). Mice were fed a HFD supplemented with 5% w/w BM (BM-HFD) for 4 weeks, and then switched to a HFD for 4 weeks. Mice fed a BM-HFD showed significantly lower body weight gain and abdominal fat, compared to the HFD. Furthermore, a BM-HFD significantly reduced plasma and hepatic total and low-density lipoprotein (LDL)-cholesterol, compared to HFD. The decrease in cholesterol levels coincided with inhibition of hepatic sterol regulatory element-binding protein-2 and HMG-CoA reductase mRNA expression, and an increase in LDL-receptor gene expression in the BM-HFD group, compared to the HFD group. In conclusion, our findings have established that BM reduces body weight gain in mice. BM may have potential to lower cholesterol levels by inhibiting cholesterol synthesis, thereby protecting against obesity and perhaps heart disease.