In spring 2013, groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by perfluoroalkyl substances (PFAS) from a PFAS manufacturing plant active since the ...late 1960s. Residents were exposed to high concentrations of PFAS, particularly perfluorooctanoic acid (PFOA), through drinking water until autumn 2013. A publicly funded health surveillance program is under way to aid in the prevention, early diagnosis, and treatment of chronic disorders possibly associated with PFAS exposure.
The objectives of this paper are:
) to describe the organization of the health surveillance program,
) to report serum PFAS concentrations in adolescents and young adults, and
) to identify predictors of serum PFAS concentrations in the studied population.
The health surveillance program offered to residents of municipalities supplied by contaminated waterworks includes a structured interview, routine blood and urine tests, and measurement of 12 PFAS in serum by high-performance liquid chromatography-tandem mass spectrometry. We studied 18,345 participants born between 1978 and 2002, 14-39 years of age at recruitment. Multivariable linear regression was used to identify sociodemographic, lifestyle, dietary, and reproductive predictors of serum PFAS concentrations.
The PFAS with the highest serum concentrations were PFOA median
, interquartile range (IQR) 19.3-84.9, perfluorohexanesulfonic acid (PFHxS) (median
, IQR 1.9-7.4), and perfluorooctanesulfonic acid (PFOS) (median
, IQR 2.6-5.8). The major predictors of serum levels were gender, municipality, duration of residence in the affected area, and number of deliveries. Overall, the regression models explained 37%, 23%, and 43% of the variance of PFOA, PFOS, and PFHxS, respectively.
Serum PFOA concentrations were high relative to concentrations in populations with background residential exposures only. Interindividual variation of serum PFAS levels was partially explained by the considered predictors. https://doi.org/10.1289/EHP5337.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new ...cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. Curcumin analogues like IND-4, FLLL, GO-Y030 and C086 have demonstrated to produce greater cytotoxicity when experimentally studied and study results from many have been suggested to be the same. Combination of curcumin with therapeutic cancer agents like tolfenamic acid, 5-fluorouracil, resveratrol and dasatinib showed improved cytotoxicity and chemotherapeutic effect. The results propose that employment of curcumin with novel drug delivery systems like liposome, micelles and nanoparticle have been performed which could improve the therapeutic efficacy against colon cancer. The present review highlights the mechanism of action, synergistic effect and novel delivery methods to improve the therapeutic potential of curcumin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been ...consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters.
Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20-64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals.
We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47-4.71), HDL-C (β: 1.13, 95% CI: 0.92-1.33) and LDL-C (β: 3.14, 95% CI: 2.65-3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5-4.58), HDL-C (ψ: 1.07, 95% CI 20.87-1.27) and LDL-C (ψ: 2.71, 95% CI 2.23-3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender.
The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.
This paper focuses on evaluating stress intensity factors (SIFs), for a curved beam of circular cross section with an external ring crack, applying an approach on the basis of estimating the strain ...energy release rate. The out of plane vibration of the beam is investigated. This approach requires an additional factor namely correction factor, on the basis of the energy release zone slope to approximate the SIFs. The initial curvature of the beam, however, adds some complication in using this factor. The second part of this study is investigating a numerical approach namely differential quadrature element method (DQEM) to gain the natural frequencies of the cracked beam. This method is applied to show the application of the SIFs to calculate the compliance of the cracked section for modeling the crack. The other method which is used to obtain the natural frequencies is the finite element method (FEM). The results of these two methods are found to be in good agreement, which shows the precision of the stress intensity factors of the cracked beam.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Endometriosis is a chronic inflammatory disease associated with the growth and proliferation of endometrial‐like tissues outside the uterus. Although the exact etiology and mechanism of ...the pathogenesis of the disease have not been fully elucidated, the immune system cells and the mediators produced by them can be named as effective factors in the onset and progression of the disease.
Aims
We aim to attempt to review studies on the role of the immune system in endometriosis to better understand the pathogenesis of endometriosis.
Content
Abundant production of inflammatory mediators by neutrophils and macrophages and reduced cytotoxicity of defined cells promote endometriosis at the early stages of the disease. Following an increase in the inflammation of the environment, the body takes compensatory mechanisms to reduce inflammation and establish homeostasis. For this purpose, the body produces remodeling and anti‐inflammatory factors leading to slow conversion of the inflammatory environment into a non‐inflammatory environment with proliferative and immunosuppressive properties. Environmental conditions induce M2 macrophages, TH2 cells, and Tregs differentiation, promoting disease progression by producing angiogenic and immunosuppressive factors. However, the exact molecular mechanism involved in changing inflammatory to non‐inflammatory conditions is not yet fully understood.
Implications
Due to the common characteristics of endometriotic cells and cancer cells, most potential treatment options for endometriosis have been suggested due to the results of these methods in the treatment of cancer. In this pathway, immune system cells and soluble mediators can be used as targets.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Nowadays, increasing awareness of environment and fossil fuels protection stimulates intensive research on clean and renewable sources of energy. Production of hydrogen from water through ...solar-driven splitting reactions is one of the most promising approaches in the field of photoelectrochemistry (PEC). In this work we have fabricated well-aligned, highly-ordered, smooth-mouth TiO2 nanotube arrays (TNAs) in a two-step anodization process of titanium foil, which were then used as photoelectrodes for PEC water splitting. It demonstrates for the first time correspondence between non-linear component characteristics of multiscale rough surface and crystalline structure of annealed TNAs measured at various fabrication stages and their photoelectrochemical response. The as-anodized TNAs with isotropic surface (deduced from AFM and SEM images) and largest figure of merit (according to their PEC performance) were annealed at 450 °C in air. Scale-invariant descriptors of the surface structure of the deposits involved: fractal dimension, corner frequency, roughness, size of nanostructures and their dominant habits. Moreover, X-ray diffraction data processed using the Rietveld method confirmed co-existence of various oxides, for example: TiO2 in the form of anatase, TiO and Ti3O5 phases in the TNAs under study pointing that previous well-established mechanisms of the TNA growth were to certain degree incomplete.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Glucokinase is a key enzyme which converts glucose into glucose‐6‐phosphate in the liver and pancreatic cells of the human. In the liver, glucokinase promotes the synthesis of glycogen, and in the ...pancreas, it helps in glucose‐sensitive insulin release. It serves as a “glucose sensor” and thereby plays an important role in the regulation of glucose homeostasis. Due to this activity, glucokinase is considered as an attractive drug target for type 2 diabetes. It created a lot of interest among the researchers, and several small molecules were discovered. The research work was initiated in 1990. However, the hypoglycemic effect, increased liver burden, and loss of efficacy over time were faced during clinical development. Dorzagliatin, a novel glucokinase activator that acts on both the liver and pancreas, is in the late‐stage clinical development. TTP399, a promising hepatoselective GK activator, showed a clinically significant and sustained reduction in glycated hemoglobin with a low risk of adverse effects. The successful findings generated immense interest to continue further research in finding small molecule GK activators for the treatment of type 2 diabetes. The article covers different series of GK activators reported over the past decade and the structural insights into the GK‐GK activator binding which, we believe will stimulate the discovery of novel GK activators to treat type 2 diabetes.
2‐D interaction diagram with crucial interactions between glucokinase and glucokinase activator.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Coronaviruses, which were discovered in 1968, can lead to some human viral disorders, like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome-related (MERS), and, recently, ...coronavirus disease 2019 (COVID-19). The coronavirus that leads to COVID-19 is rapidly spreading all over the world and is the reason for the deaths of thousands of people. Recent research has revealed that there is about 80% sequence homology between the coronaviruses that cause SARS and COVID-19. Considering this fact, we decided to collect the maximum available information on targets, structures, and inhibitors reported so far for SARS-CoV-1 that could be useful for researchers who work on closely related COVID-19. There are vital proteases, like papain-like protease 2 (PL2pro) and 3C-like protease (3CLpro), or main protease (Mpro), that are involved in and are essential for the replication of SARS coronavirus and so are valuable targets for the treatment of patients affected by this type of virus. SARS-CoV-1 NTPase/helicase plays an important role in the release of several non-structural proteins (nsps), so it is another essential target relating to the viral life cycle. In this paper, we provide extensive information about diverse molecules with anti-SARS activity. In addition to traditional medicinal chemistry outcomes, HTS, virtual screening efforts, and structural insights for better understanding inhibitors and SARS-CoV-1 target complexes are also discussed. This study covers a wide range of anti-SARS agents, particularly SARS-CoV-1 inhibitors, and provides new insights into drug design for the deadly SARS-CoV-2 virus.
Since the coronaviruses that cause COVID-19 and SARS-CoV-1 share 80% structural similarity, we present a comprehensive review of the diverse molecular inhibitors of SARS-CoV-1. This will help to accelerate drug discovery for deadly coronavirus diseases.
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IJS, KILJ, NUK, UL, UM, UPUK
Metal pollution in aquatic ecosystems has created concern due to its toxicity, environmental stability and ability to transfer into the food chain, and monitoring the metal source is one way to ...decrease the environmental impact. The present study aimed to investigate metal concentrations of Al, Fe, Mg, P, As, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, V and Zn, their spatial distribution, origin of the contaminants, contamination factor (CF), pollution load index (PLI), enrichment factor (EF), and geoaccumulation index (I
) in surface sediments of the Amir-Kalayeh wetland. Using statistical methods such as Pearson correlation coefficient, cluster analysis and factor analysis, the natural or anthropogenic origin of these elements was determined. According to the results, As, Cd, Mn, Mo And Pb have CFs higher than 1, which means they have contaminated the area. In this research, PLI was 0.9, which means the sediments of Amir-Kalayeh wetland are not polluted. The highest EF belongs to Mn and Mo. Determining I
showed that none of the metals in Amir-Kalayeh wetland are within the pollution range. However, the enrichment of elements in the sediments shows that continuous monitoring and managing of metal pollution source in this wetland is an essential step.
This study aimed at exploring the extent of likely sources of heavy metal pollution in sediments of the Khajeh Kory riverbed in the north of Iran. In order to assess the heavy metal contamination, ...samples from surface sediments in 10 stations covering the river were collected and analysed to determine heavy metal contents including Cd, Cu, Ni, Pb, Zn, Mn, Co, Al, and Fe. Three guidelines were applied to assess the heavy metal contamination. Compared with the global average values, the calculated enrichment factors indicated high values for Fe, Mn, Cd, Co, and Cu, and very high values for Pb and Zn. The results obtained from principal component analysis revealed that the geogenic and anthropogenic sources were the main causes of the widespread enrichment of heavy metals in the riverbed sediments. The results suggested that the riverbed sediments were contaminated with heavy metals, which contribute to the freshwater toxicity in the ecosystem of the Khajeh Kory River.
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