Mechanism of Astragalus membranaceus (Huangqi, HQ) for treatment of heart failure based on network pharmacology and molecular docking.

Heart failure is a leading cause of death in the elderly. Traditional Chinese medicine, a verified alternative therapeutic regimen, has been used to treat heart failure, which is less expensive and has fewer adverse effects. In this study, a total of 15 active ingredients of Astragalus membranaceus (Huangqi, HQ) were obtained; among them, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol were found to be linked to heart failure. Ang II significantly enlarged the cell size of cardiomyocytes, which could be partially reduced by Quercetin, Isorhamnetin, Calycosin, Kaempferol, or Formononetin. Ang II significantly up-regulated ANP, BNP, ß-MHC, and CTGF expressions, whereas Quercetin, Isorhamnetin, Calycosin, Kaempferol or Formononetin treatment partially downregulated ANP, BNP, ß-MHC and CTGF expressions. Five active ingredients of HQ attenuated inflammation in Ang II-induced cardiomyocytes by inhibiting the levels of TNF-α, IL-1ß, IL-18 and IL-6. Molecular docking shows Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol can bind with its target protein ESR1 in a good bond by intermolecular force. Quercetin, Calycosin, Kaempferol or Formononetin treatment promoted the expression levels of ESR1 and phosphorylated ESR1 in Ang II-stimulated cardiomyocytes; however, Isorhamnetin treatment had no effect on ESR1 and phosphorylated ESR1 expression levels. In conclusion, our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HQ against heart failure. Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure through regulating ESR1 expression, which provided a basis for the clinical application of HQ to regulate cardiac hypertrophy and heart failure.

Changes in the shape and function of the fetal heart of pre- and gestational diabetes mothers.

BACKGROUND: Hyperglycemia during pregnancy can affect fetal heart in many ways, including causing cardiac malformation, leading to hypertrophic cardiomyopathy and cardiac dysfunction. Echocardiographic evaluation can assist identify alterations in heart structure, morphology and function, enabling prompt monitoring and management. However, according to earlier research, the cardiac alterations are modest in hyperglycemic mothers' fetuses, and might not be detectable using conventional methods and it is also unclear whether these changes are related to the metabolism of mothers. Fetal Heart Quantification (Fetal HQ) can assess ventricular geometry and function more sensitively and thoroughly, and identify sub-clinical cardiac dysfunction. The purpose of this study was to evaluate fetal heart by Fetal HQ in fetuses of hyperglycemic mothers who either had pre-gestational or gestational diabetes and to correlate them with maternal metabolic indices. METHODS: The fetuses of 25 gestational age-matched control mothers, 48 women with gestational diabetes mellitus (GDM), and 11 women with diabetes mellitus (DM) were included in the prospective case-control research. Using fetal echocardiography and speckle tracking echocardiography (STE), the heart of the fetus was evaluated. Differences in the groups' anthropometric, metabolic, and cardiac parameters were examined. It was assessed whether maternal features, prenatal glucose, lipids, and maternal hemoglobin A1c (HbA1c) correlated with fetal cardiac parameters. RESULTS: The LV EDV and ESV were significantly higher in the GDM group as compared to the DM group (p < 0.05). The GSI% was significantly lower in the GDM group compared with the control (p < 0.05). The LV SV and CO of the GDM group were both significantly higher compared with the DM group (p < 0.05). There was a significant decrease in RV FS for segments 1-7 in GDM fetuses compared to the control (p < 0.05) and for segments 5-10 compared to DM (p < 0.05). Fetal cardiac morphology and function indices correlate with maternal pregestational weight, BMI, early pregnancy fast glucose, lipids, and glycemic control levels. CONCLUSIONS: Fetuses exposed to gestational diabetes have altered heart morphology and function that is linked to maternal metabolic parameters, which presents a special indication for performing geometry and function cardiac assessment. Fetal HQ can be employed to evaluate the fetal cardiac shape and function in fetuses exposed to gestational diabetes.

Utility of the novel fetal heart quantification (fetal HQ) technique in diagnosing ventricular interdependence and biventricular dysfunction in a case of prenatally diagnosed Uhl's anomaly.

Uhl's anomaly is characterized by complete or partial absence of right ventricular myocardium. We describe a case of prenatally diagnosed Uhl's anomaly with biventricular dysfunction which was quantified with speckle tracking echocardiography using a novel fetal heart quantification (fetal HQ) technique.

One-step solvent thermal synthesis of 3D networked MOF composites for preparation of an ultrasensitive chemosensor for hydroquinone and catechol.

Pharmaceuticals and personal care products (PPCPs) have a significant impact on the environment and human health, due to their sometimes toxic and carcinogenic characteristics. Therefore, an innovative chemosensor was constructed for ultrasensitive determination of two typical PCCPs (hydroquinone (HQ) and catechol (CC)) in several minutes. The homemade chemosensor (UiO-67@GO/MWCNTs) consisted of MOF(UiO-67), graphene oxide (GO), and multi-walled carbon nanotubes (MWCNTs) composites; it was a networked, structurally sparse, porosity-rich, homogeneous octahedral composite, and had ultra-high electrical conductivity, which provided lots of active adsorption sites, promote charge transfer, and enrich lots of molecules to be measured in a few minutes. The prepared electrochemical sensor showed good long-term stability, applicability, reproducibility, and immunity to interference for the determination of HQ and CC, with a wide linear range of response of 5.0 ~ 940 µM for both HQ and CC, and a low limit of detection with satisfactory recoveries. In addition, a new strategy of using MOF composites as the basis for electrochemical determination of organic small molecules was established, and a new platform was constructed for the quantitative determination of organic small molecules in various environmental samples.

Mercury risk assessment scenarios: exposure from fish dietary behaviors of Katingan River Basin community.

Katingan River has been contaminated by mercury from ASGM activities since the early 2000s. This study aims to assess the risk of mercury exposure from Katingan fish consumption and analyze relationships between exposure variables. We proposed two risk assessment scenarios based on mercury analysis of 74 fish samples and fish consumption questionnaire. The risk assessment result revealed that estimated daily intakes (EDIs) of Scenario 2 were generally 3-4 times higher than Scenario 1. The statistical test results showed significant differences (p < 0.05) in EDI values between scenarios, indicating that variations in fish consumption influenced the mercury intake. Three different health reference-based values (HRVs) were applied in estimating the hazard quotient (HQ) and it influenced the HQ results (p < 0.05), for both scenarios. The relationship analysis between variables presented a strong non-linear correlation between EDI and hair mercury level for both scenarios, but a weak relationship between age and hair mercury level.

Phosphorus-Containing Polybenzoxazine Aerogels with Efficient Flame Retardation and Thermal Insulation.

Bisphenol A type benzoxazine (Ba) monomers and 10-(2, 5-dihydroxyphenyl)-10- hydrogen-9- oxygen-10- phosphine-10- oxide (DOPO-HQ) were employed to prepare flame retardant and heat insulated polybenzoxazine (PBa) composite aerogels. The successful preparation of PBa composite aerogels was confirmed by Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The thermal degradation behavior and flame-retardant properties of the pristine PBa and PBa composite aerogels were investigated with thermogravimetric analysis (TGA) and cone calorimeter. The initial decomposition temperature of PBa decreased slightly after incorporating DOPO-HQ, increasing the char residue amount. The incorporation of 5% DOPO-HQ into PBa led to a decrease of 33.1% at the peak of the heat-release rate and a decrease of 58.7% in the TSP. The flame-retardant mechanism of PBa composite aerogels was investigated by SEM, Raman spectroscopy, and TGA coupled with infrared spectrometry (TG-FTIR). The aerogel has advantages such as a simple synthesis procedure, easy amplification, lightweight, low thermal conductivity, and good flame retardancy.

Occurrence and exposure risk assessment of organochlorine pesticides in two waterbird species from Honghu Lake Wetland, Central China.

Monitoring and evaluating bird exposure to hazardous pollutants in wetlands are receiving considerable attention. In this study, the occurrence of 18 organochlorine pesticides (OCPs) in the muscle of bean geese (Anser fabalis) and common teals (Anas crecca) collected from Honghu Lake Wetland (HLW), Central China was studied. Additionally, an exposure risk assessment model was applied to obtain risk levels of OCPs to these birds through three oral routes (food intake, water drinking and soil ingestion). The results suggested that the most abundant OCPs detected in the muscle of waterbirds were DDTs (7.68-602 ng/g lipid weight), followed by HCHs (1.39-89.8 ng/g lipid weight). A significant difference (p < 0.05) existed between two species, but most of OCPs exhibited no statistically relationship with age or gender (p > 0.05). The compositional patterns of OCPs combined with ratios of certain metabolites to their parent compounds indicated that all OCPs in the HLW were largely from historical usage except heptachlor. The exposure risk assessment revealed that common teals with lighter weight had greater exposure risks than bean geese. Of the OCPs analyzed, DDTs could probably cause harm to target birds studied here. Exposure via food intake was identified to be significant while soil ingestion and water drinking contributed least, but they should still be concerned.

Histone demethylase JMJD2D promotes the self-renewal of liver cancer stem-like cells by enhancing EpCAM and Sox9 expression.

Cancer stem-like cells (CSCs) contribute to the high rate of tumor heterogeneity, metastasis, therapeutic resistance, and recurrence. Histone lysine demethylase 4D (KDM4D or JMJD2D) is highly expressed in colon and liver tumors, where it promotes cancer progression; however, the role of JMJD2D in CSCs remains unclear. Here, we show that JMJD2D expression was increased in liver cancer stem-like cells (LCSCs); downregulation of JMJD2D inhibited the self-renewal of LCSCs in vitro and in vivo and inhibited the lung metastasis of LCSCs by reducing the survival and the early lung seeding of circulating LCSCs. Mechanistically, JMJD2D promoted LCSC self-renewal by enhancing the expression of CSC markers EpCAM and Sox9; JMJD2D reduced H3K9me3 levels on the promoters of EpCAM and Sox9 to enhance their transcription via interaction with ß-catenin/TCF4 and Notch1 intracellular domain, respectively. Restoration of EpCAM and Sox9 expression in JMJD2D-knockdown liver cancer cells rescued the self-renewal of LCSCs. Pharmacological inhibition of JMJD2D using 5-c-8HQ reduced the self-renewal of LCSCs and liver cancer progression. Collectively, our findings suggest that JMJD2D promotes LCSC self-renewal by enhancing EpCAM and Sox9 expression via Wnt/ß-catenin and Notch signaling pathways and is a potential therapeutic target for liver cancer.

Dynamic pressure-flow curve analysis of the native heart and left ventricular assist device for full and partial bypass conditions.

BACKGROUND: During left ventricular assist device (LVAD) support, the external work performed by the native heart combines with the work performed by the rotary LVAD to provide cyclic flow through the LVAD and, in some conditions, through the aortic valve. In this study, a balance of external work was developed and validated for both full and partial bypass conditions that includes valve opening and aortic compliance. METHODS: The theory assumes a steady-state contribution of external work from the rotary LVAD and a dynamic portion from the heart. Cyclic flow may be ejected through either the LVAD or ascending aorta, and an energy absorption term accounts for aortic compliance. Mock loop studies were performed for LV ejection fractions of 10%-28% combined with HeartMate II LVAD support at 8 and 11 krpm to produce a range of full and partial bypass conditions. The external work of the LVAD and native heart was computed from the experimental pressure-flow (H-Q) relations and compared to the theory. RESULTS: Native heart contraction produces a counterclockwise loop in the pressure-flow relation of the LVAD which increased with ejection fraction, and during full bypass conditions the external work was preserved in the total systemic flow. During partial bypass conditions, forward flow through the ascending aorta was accompanied by a reversal during aortic valve closure resulting in a reduction in energy in the downstream flow. CONCLUSIONS: The study presents a balance of external work during full and partial bypass LVAD support. Experimental data validated the additional terms corresponding to forward flow and aortic compliance that contribute to the system balance. This expanded theory can be applied to LVAD design and control to improve pulsatility and aortic valve biomechanics.

The effect of gracilis tendon harvesting in addition to semitendinosus tendon harvesting on knee extensor and flexor strength after anterior cruciate ligament reconstruction.

INTRODUCTION: Anterior cruciate ligament (ACL) reconstruction using hamstring tendons may involve harvesting of the gracilis tendon in addition to the semitendinosus tendon (ST) depending on the size of the ST graft. However, the effect of gracilis harvesting in addition to ST harvesting on muscle strength, such as the hamstring-to-quadriceps (HQ) ratio, remains unclear. Hence, this study aimed to investigate the effect of gracilis harvesting on subsequent knee muscle strength. MATERIALS AND METHODS: Eighty-two patients who underwent ACL reconstruction were included in this retrospective study. They were divided into the following two groups depending on the tendon graft used for ACL reconstruction: the ST group (41 patients) and the semitendinosus tendon/gracilis tendon (STG) group (41 patients). The isokinetic peak torque of the knee extensor and flexor was measured using a BIODEX dynamometer at a velocity of 60°/s and 180°/s, respectively, 3 and 6 months after ACL reconstruction. The groups were compared in terms of the limb symmetry index (LSI) and HQ ratio. RESULTS: The significant difference in the knee flexor of the LSI at 6 months after ACL reconstruction was as follows: ST group, 120.3 ± 28.3 vs STG group, 105.6 ± 19.0 (p < 0.01) at 60°/s and ST group, 122.9 ± 35.2 vs STG group, 106.2 ± 24.6 (p = 0.02) at 180°/s. There were significant differences in the HQ ratio at 180°/s as follows: ST group, 0.67 ± 0.15 vs STG group, 0.60 ± 0.13 (p < 0.01) at 3 months and ST group, 0.67 ± 0.13 vs STG group, and 0.59 ± 0.12 (p < 0.01) at 6 months after ACL reconstruction. CONCLUSIONS: Gracilis tendon harvesting may contribute to a decrease in knee flexor strength and HQ ratio with fast contraction. Thus, the need for gracilis tendon harvesting in ACL reconstruction should be carefully considered. LEVEL OF EVIDENCE: III.

Comparing the relative robustness of byproduct removal by wash and by elution in column chromatography for the purification of a bispecific antibody.

For recombinant antibody purification, removal of product-related impurities usually relies on the two polishing steps post Protein A chromatography. A certain impurity may bind weaker or tighter to a particular type of column than the target antibody, and this forms the basis for separation. For impurities that bind weaker, they can be removed by pre-elution wash under appropriate conditions. For impurities that bind stronger, they can be separated by using a suitable condition that selectively elutes the product. In this study, with a bispecific antibody case, we compared the relative robustness of byproduct removal by wash and by elution using two different types of chromatography. The data suggest that elution-enabled byproduct clearance is more robust than wash-enabled clearance, and the former approach provides consistent impurity clearance over a relatively wide range of loading density.

Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study.

BACKGROUND: Due to metabolic changes in the second trimester and the increasing number of pregnant women with obesity and advanced maternal age, the incidence of gestational diabetes mellitus (GDM) remains high. This study aimed to evaluate the effects of GDM on fetal cardiac morphology and function, and to determine whether these changes increase with increasing estimated fetal weight (EFW). METHODS: Fifty-eight women with GDM (GDM group) and 58 women with a healthy pregnancy (control group) were included in this prospective observational cohort study. Each group included subgroups of 31 pregnant women with a gestational age between 24+0 weeks and 27+6 weeks as well as 27 pregnant women with a gestational age between 28+0 weeks and 40+0 weeks. For all fetuses, a cine of 2-3 s in the four-chamber view was obtained, and online speckle-tracking analysis was performed using the GE Automatic Fetal Heart Assessment Tool (fetal HQ; General Electric Healthcare Ultrasound, Zipf, Austria) to measure the global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), 24-segment sphericity index (SI), and 24-segment end-diastolic diameter of the left ventricle (LV) and right ventricle (RV). Data were analyzed using the independent t-test and Wilcoxon rank-sum test, as applicable. RESULTS: The GDM group (mean HbA1c value was 5.3 ± 0.57 mmol/L) showed a lower GSI value than the control group (1.21 vs. 1.27, P = 0.000), which indicated a rounder shape of the heart. In addition, fetuses in the GDM group demonstrated significant impairment in cardiac function compared to those in the control group (LV-GLS: -18.26% vs. -22.70%, RV-GLS: -18.52% vs. -22.74%, LV-FAC: 35.30% vs. 42.36%, RV-FAC: 30.89% vs. 36.80%; P = 0.000 for all). Subgroup analyses according to gestational age (24+0-27+6 weeks and 28+0-40+0 weeks) showed that the statistical differences were retained between the GDM and control groups in each subgroup. CONCLUSIONS: Fetuses of women with GDM present with signs of biventricular systolic dysfunction according to deformation analysis using fetal HQ. Additionally, the heart had a rounder shape in the GDM group than in the control group. This study showed that fetal HQ can be used to assess fetal cardiac morphology and function easily and quickly, and the effects of GDM on fetal cardiac morphology and function appeared from the second trimester. Thus, whether earlier and stricter clinical intervention was necessary remained to be further studied. Furthermore, future studies will need to supplement the effects of blood glucose levels on GLS, FAC, GSI, and 24-segment SI. Additionally, the long-term follow-up after birth should also be improved to observe the influence of changes in the indicators on the prognosis.

Source characterization and health risks of BTEX in indoor/outdoor air during winters at a terai precinct of North India.

BTEX are the consistently found air contaminants in indoor and outdoor environments. In order to investigate the exposure levels of BTEX, the indoor and outdoor air was analyzed during winter season at homes located at four selected sites of Gorakhpur, Uttar Pradesh, India, which comprised residential, roadside, industrial and agricultural areas. BTEX were sampled with a low-flow pump (SKC model 220). Samples were extracted with CS2 and the aromatic fraction was subjected to GC-FID. Mean indoor concentration of BTEX was highest at the agricultural (70.9 µg m-3) followed by industrial (30.0 µg m-3), roadside (17.5 µg m-3) and residential site (11.8 µg m-3). At outdoor locations, the mean BTEX levels were highest at the roadside (22.0 µg m-3) followed by industrial (18.7 µg m-3), agricultural (11.0 µg m-3) and residential site (9.1 µg m-3). The I/O ratios were greater than 1 at all the sites except roadside site, where I/O ratios for toluene, ethylbenzene and xylene were less than unity. Poor correlation between indoor and outdoor levels at each site further indicated the dominance of indoor sources. Factor analysis followed by one-way analysis of variance depicts that the presence of BTEX compounds at all the sites indicate a mixture of vehicular and combustion activities. For benzene, the ILTCR values exceeded the safe levels, whereas ethylbenzene was nearby to the recommended level 1 × 10-6. The HQ values were above unity for agricultural (indoors) and industrial (outdoors) as an exception to all the other sites which indicted the value below unity.

Revealing drinking water quality issues and possible health risks based on water quality index (WQI) method in the Shanmuganadhi River basin of South India.

The aim of the study is to address the issues and associated health risks due to consumption of high-fluoride water supplied for drinking in a rural part of Shanmuganadhi River basin, Tamil Nadu, India. In this study, 61 groundwater samples were gathered from various tube and open wells and analysed for fluoride and other physicochemical parameters. The abundance of cations is Na+ > Ca2+ > Mg2+ > K+, and that of anions is HCO3- > SO42- > Cl- > F-. The fluoride concentration in drinking groundwater varied from 0.10 to 3.3 mg/l. According to the WHO standards, about 26% of the samples were unfit for drinking requirements (16 out of 61 samples) Water quality index (WQI) method was adopted to categorize the water into different classes to understand its suitability for drinking requirements. WQI signified that nearly 52% of the samples denoted poor, very poor and not suitable categories, whereas 48% of samples denoted good and excellent categories for consumption. Health risks associated with high-fluoride drinking water were assessed for various age groups of inhabitants such as children, teens and adults. The hazard quotient estimated based on the oral intake ranged from 0.00E+00 to 5.50E+00, from 0.00E+00 to 4.22E+00 and from 0.00E+00 to 3.45E+00 for children, teens and adults, respectively. It suggested that the health risks are associated with 75%, 59% and 43% of samples, respectively, among children, teens and adults. Therefore, children are more inclined towards risk than teens and adults in this region based on the intake of fluoride-rich drinking water. To improve the present scenario, groundwater should be either treated before drinking water supply or must be artificially recharged to lower the concentration of ions.

Health risk assessment of heavy metals exposure via consumption of crops grown in phosphogypsum-contaminated soils.

The management of phosphogypsum (PG) heap, located south of the Sfax city in Tunisia, has been going on for decades. But dumping this solid waste still poses environmental problems. Even though valorized as amendment to agriculture soils, the sanitary impact of this practice is not seriously considered. To assess the risk of the transference of contaminants from PG to agricultural soil-plants food chain, a wild plant species Salicornia arabica grown in PG-contaminated field and tomato (Lycopersicon esculentum) and oat (Avena sativa) grown in laboratory using different rates (10, 20 and 30%) of PG amendment, were tested. The cadmium, lead, chromium, nickel, copper and zinc concentrations in soils and plants were determined by atomic absorption spectrometry and by inductively coupled plasma-mass spectrometry, respectively. Measurements showed that Ni, Cu and Pb levels in the amended soils were below international standards except for Cd and Cr which exceeded Chinese, FAO/WHO and European allowable standard limits. Gathered results showed that the more the PG rate increases, the more the bioconcentration factors of heavy metals increased in plants, particularly in the roots. This is a prospective study assuming direct or indirect exposure scenario of different human cohorts by consuming varied common food stuffs. The Human Exposure to Soil Pollutants evaluation and United State Environment Protection Agency models were adopted for the hazard quotient calculation to assess the acceptability of sanitary risk related to each metal. The direct and indirect health risk assessments varied in the decreasing order: children, adolescents and then adults. Therefore, the PG amendment must not exceed the rate of 10%.

Pesticide Residues and Health Risk Assessment in Tomatoes and Lettuces from Farms of Metropolitan Region Chile.

Over the last years, the detection of pesticide residues in the official food surveillance programs of Chile has been increased, mainly in fresh vegetables such as tomatoes and lettuces. The Metropolitana Region of Chile presents the highest detections in the country. The lack of evaluations of toxicological risks in human health have increased uncertainty of the potential effects of pesticides exposures in the Chilean population. This research aims to determinate health risks assessment of pesticide residues associated to tomatoes and lettuces produced in Metropolitana Region. The findings of this study reveal that tomatoes and lettuces cultivated in the MR show more than 50% of samples with one or multiple pesticides residues. From the total samples, 16% were over the Chilean Maximum Residue Levels (MRLs). The main pesticides detected in tomatoes and lettuces were methamidophos, methomyl, difenoconazole, cyprodinil and boscalid. The results obtained using the official data of the Ministry of Health of Chile (MINSAL) compared to the World Health Organization (WHO), describe relevant risks through the Estimated Daily Intakes (EDI), Hazard Quotients (HQ) and Hazard Index (HI) for the Chilean population due to high concentrations of methamidophos, methomyl and cyprodinil. More restrictions for the use of methamidophos, methomyl, difenoconazole, cyprodinil and boscalid and effective control programs should be implemented in order to mitigate the impacts on the Chilean population.

Evaluation of heavy metals in cosmetic products and their health risk assessment.

Heavy metals' contamination in cosmetic products is a serious threat. Present study was conducted to evaluate the concentrations of heavy metals (HMs) in various brands of cosmetic products with special emphasis on their health risk assessment. Five heavy metals including Cd, Cr, Fe, Ni and Pb were quantified in different brands of lotions, foundations, whitening creams, lipsticks, hair dyes and sunblock creams using atomic absorption spectrometry. Risk to the consumer's health was determined using systemic exposure dosage (SED), margin of safety (MoS), hazard quotient (HQ), hazard index (HI) and lifetime cancer risk (LCR). On comparative basis, different brands of sunblock creams depicted highest concentration of Ni, Pb and Cr (7.99 ± 0.36, 6.37 ± 0.05 and 0.43 ± 0.01 mg/kg, respectively), whereas lipsticks had elevated levels of Fe at 12.0 ± 1.8 mg/kg, and Cd was maximum in lotions (0.26 ± 0.02 mg/kg). Multivariate analysis revealed strong associations among Cr, Ni and Pb, while Cd and Fe showed disparity in distribution and sources of contamination. MoS, HQ and HI values were within the permissible limit apart from for lotions and sunblock creams, while LCR value was higher than the permissible limit in all cosmetic products except lipsticks. Regular use of these products can cause serious threat to human health, particularly skin cancer on long time exposure. Therefore, continuous monitoring of cosmetic products, particularly with reference to HMs adulteration should be adopted to ensure the human safety and security.

Antiplatelet, antioxidative, and anti-inflammatory effects of hydroquinone.

Platelets play crucial roles in thrombosis and hemostasis through platelet activation and aggregation that are crucial in cardiovascular diseases. Hydroquinone (HQ) and its derivatives are present in many dermatological creams, paints, motor fuels, air, microorganisms, and plant products like wheat bread, fruit, coffee, and red wine. The effect of HQ on humans is not clear. In this study, we found that HQ (>25 µM) inhibited arachidonic acid (AA)-induced platelet aggregation. HQ suppressed AA-induced thromboxane B2 production of platelets. HQ (>10 µM) also attenuated ex vivo platelet-rich plasma aggregation. HQ prevented the interleukin (IL)-1ß-induced 8-isoprostane, and PGE2 production, but not IL-8 production of pulp cells. These results indicate that HQ may have an antiplatelet effect via inhibition of thromboxane production. HQ has antioxidative and anti-inflammatory effects, and possible inhibition of COX. Exposure and consumption of HQ-containing products, food or drugs may have antiplatelet, antioxidative, and anti-inflammatory effects.

E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by hydroquinone.

Hydroquinone (HQ), one of the most significant metabolic activation products of benzene in an organism, can cause hematological toxicity, such as acute myeloid leukemia. It is a clear carcinogen that can cause changes in the disorder of cell cycle and cell growth. However, its molecular mechanisms remain unclear. E4 transcription factor 1 (E4F1), an important transcription factor, participating in the regulation of cell cycle may be related to the occurrence of tumor. Here, we examined the HQ-induced malignant transformed TK6 cells (TK6-HT) to illustrate the role of E4F1 in carcinogenesis. The present study showed that both the expressions of E4F1 messenger RNA and protein increased obviously in TK6-HT, preliminarily indicating that E4F1 is associated with HQ-induced carcinogenesis. To further explore the role of E4F1, we established E4F1 silencing TK6-HT (pLVX-shE4F1) and its control cells (pLVX-shNC) using lentiviral short hairpin RNA (shRNA) interference expression plasmid vector pLVX-shRNA. Flow cytometry and cell counting kit-8 assay were used to determine the effects of E4F1 silencing on cell cycle and cell growth, respectively. E4F1 silencing inhibited cell growth in TK6-HT. The results from flow cytometry indicated that the inhibitory effect on cell growth may be the results of the E4F1 silencing-induced accumulation in G2/M compared with TK6-HT-shNC. Meanwhile, levels of DNA damage (γ-H2AX), proteins of Rb and phosphorylated Rb, and reactive oxygen species were increased in TK6-HT-shRNA2 cells, which is the critical reason of cell-cycle arrest. In conclusion, E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by HQ.

Targeted 8-hydroxyquinoline fragment based small molecule drug discovery against neglected botulinum neurotoxin type F.

OBJECTIVES: Botulinum neurotoxins are highly potent biological warfare agents. The unavailability of countermeasures against these neurotoxins has been a matter of extensive research. However, no clinical therapeutics has come to existence till date. The 8-hydroxyquinoline (8-HQ) scaffold is established privileged compound and its potential as drug candidate against BoNTs is recently being explored. METHODS: In present work, three course studies were performed involving in silico, in vitro and in vivo cascade to screen 8-HQ small molecule inhibitors against BoNT/F intoxication. ~800 molecules obtained from open repositories were screened in silico and commercially obtained twenty-four 8-HQ derived small molecule inhibitors were evaluated against rBoNT/F light chain through fluorescence thermal shift (FTS) assay. Selected compounds were further evaluated through endopeptidase assay. Further binding affinity analysis was done through surface plasmon resonance (SPR) based Proteon™ XPR 36 system. Finally, the in vivo efficacy of these compounds was evaluated in mice model. RESULTS: Three compounds NSC1011, NSC1014 and NSC84094 were found to be highly inhibitory after screening of 8-HQ compounds through FTS assay and endopeptidase assay. SPR based protein-small molecule interaction studies showed highest affinity binding of NSC1014 (KD: 5.58E-06) with BoNT/F-LC. NSC1011, NSC1014, and NSC84094 displayed IC50 of 30.47 ±â€¯6.24, 14.91 ±â€¯2.49 and 17.39 ±â€¯2.74 µM, respectively, in endopeptidase assay. NSC1011 and NSC1014 displayed marked extension of survival time in mice model. CONCLUSION: NSC1011 and NSC1014 have emerged as promising drug candidate against BoNT/F intoxication displaying higher potential than previously reported compounds.