Groundwater quality assessment and modeling utilizing water quality index and GIS in Kabul Basin, Afghanistan.

Groundwater stands as a unique source of water supply in Kabul city, Afghanistan. In this investigation, 35 samples of groundwater were comprehensively analyzed to determine its hydrogeochemical characterizations, quality, water types, and its acceptability as drinking sources. A portable digital multiparameter instrument (LAB MAN Scientific instrument) was used to measure the total dissolved solids (TDS), hydrogen potential (pH), and electrical conductivity (EC). Total hardness, chloride, and bicarbonate were examined via a titrimetric approach. Sodium, calcium, magnesium, and potassium concentrations were measured with a flame photometer. Fluoride was determined by using a digital portable multiparameter. UV-VIS spectrophotometers were employed to count sulfate and nitrate concentrations. The distribution pattern of measured parameters and the Water Quality Index (WQI) in groundwater were spatially modeled utilizing the ArcGIS tool. The findings provide insight into the main anions and cations, which are found in ascending sequence F < NO3 < SO4 < Cl < HCO3 and K < Ca < Na < Mg, respectively. Based on the measurements of ion concentrations, bicarbonate (71.4%), chloride (14.28%), nitrate (2.85%), magnesium (80%), sodium (82.85%), calcium (5.71%), and potassium (17.14%) were all determined to be over the World Health Organization (WHO) limits of drinking water. Using the Piper trilinear diagram, two significant hydrochemical facies (CaNaHCO3 and NaHCO3) were discovered. Based on the mathematical model of WQI outputs, 88.57% of the research region has excellent to good water, whereas 11.43% has poor to very poor water.

Loss of WD2 subdomain of Apaf-1 forms an apoptosome structure which blocks activation of caspase-3 and caspase-9.

Split luciferase complementary assay has been used to investigate the effect of WD domain deletion on Apaf-1 oligomerization. Apaf-1 is an adaptor molecule in formation of apoptosome that activates caspase-9, an activation that is a key event in the mitochondrial cell death pathway. Structural studies suggest that normally Apaf-1 is held in an inactive conformation by intramolecular interactions between Apaf-1's nucleotide binding domain and one of its WD40 domains (WD1). In the prevailing model of Apaf-1 activation, cytochrome c binds to sites in WD1 and in Apaf-1's second WD40 domain (WD2), moving WD1 and WD2 closer together and rotating WD1 away from the nucleotide binding domain. This allows Apaf-1 to bind dATP or ATP and to form the apoptosome, which activates caspase-9. This model predicts that cytochrome c binding to both WD domains is necessary for apoptosome formation and that an Apaf-1 with only WD1 will be locked in an inactive conformation that cannot be activated by cytochrome c. Here we investigated the effect of removing one WD domain (Apaf-1 1-921) on Apaf-1 interactions and caspase activation. Apaf-1 1-921 could not activate caspase-9, even in the presence of cytochrome c. These data show that a single WD domain is sufficient to lock Apaf-1 in an inactive state and this state cannot be altered by cytochrome c.

The long-term effects of Δ9-tetrahydrocannabinol on microtubule dynamicity in rats.

Studies reported that Δ9-tetrahydrocannabinol (Δ9-THC) is an essential drug as an anti-cancer, neuroprotective, anti-inflammatory, and immune-modulatory agent. However, the mechanism by which Δ9-THC causes these events remains to be elucidated. We attempted to investigate the in vivo studies of Δ9-THC on brain microtubule dynamicity, and acetylcholinesterase (AChE) activity. The microtubule polymerization, secondary and tertiary structures of α/ß-tubulins, as well as the AChE activity, were evaluated in the experimental groups. The significantly lowest optical density and initial rate of polymerization was observed in THC 3 mg/kg, THC 9 mg/kg, and THC 18 mg/kg treated groups. The content of secondary and tertiary structures of α/ß-tubulins was significantly affected in treated groups. The AChE activity was significantly lower in treated groups in a dose-dependent manner. These data highlight the microtubule dynamicity as a molecular target for Δ9-THC, which affects memory dysfunction. However, Δ9-THC can be inhibited the AChE activity and provide an improved therapeutics for neurodegenerative diseases.

Mounting evidence validates Ursolic Acid directly activates SIRT1: A powerful STAC which mimic endogenous activator of SIRT1.

Ursolic Acid (UA), a pentacyclic triterpenoid compound, plays a vital role in aging process. However, the role of UA in the regulation of aging and longevity is still controversial as we have previously demonstrated that UA increases SIRT1 protein level in aged-mice. Here, we reveal that UA directly activates SIRT1 in silico, in vitro and in vivo. We have identified that UA binds to outer surface of SIRT1 and leads to tight binding of substrates to enzyme in comparison with Resveratrol (RSV) and control. Furthermore, our results indicate that UA drives the structure of SIRT1 toward a closed state (an active form of enzyme). Interestingly, our experimental findings are in agreement with the molecular dynamic results. Based on our data, UA increases the affinity of enzyme for both substrates with decreasing Km value, while enhances the Vmax of enzyme. Additionally, we have determined that UA heightened SIRT1 catalytic efficiency by 2 folds compared with RSV. Thereby, to identify the endogenous activator of SIRT1, UA was administrated to aged-mice and then the tissues were isolated. According to our results, it can be concluded that UA increases SIRT1 activity and mimics Lamin A and AROS behavior in the living cells.

Apoptosome formation upon overexpression of native and truncated Apaf-1 in cell-free and cell-based systems.

Apaf-1 is a cytosolic multi-domain protein in the apoptosis regulatory network. When cytochrome c releases from mitochondria; it binds to WD-40 repeats of Apaf-1 molecule and induces oligomerization of Apaf-1. Here in, a split luciferase assay was used to compare apoptosome formation in cell-free and cell-based systems. This assay uses Apaf-1 tagged with either N-terminal fragment or C-terminal fragment of P. pyralis luciferase. In cell based-system, the apoptosome formation is induced inside the cells which express Apaf-1 tagged with complementary fragments of luciferase while in cell-free system, the apoptosome formation is induced in extracts of the cells. In cell-free system, cytochrome c dependent luciferase activity was observed with full length Apaf-1. However, luciferase activity due to apoptosome formation was much higher in cell based system compared to cell-free system. The truncated Apaf-1 which lacks WD-40 repeats (ΔApaf-1) interacted with endogenous Apaf-1 in a different fashion compared to native form as confirmed by different retention time of eluate in gel filtration and binding to affinity column. The interactions between endogenous Apaf-1 and ΔApaf-1 is stronger than its interaction with native exogenous Apaf-1 as indicated by dominant negative effect of ΔApaf-1 on caspase-3 processing.

Efficacy of Intravenous Paracetamol Versus Intravenous Morphine in Acute Limb Trauma.

BACKGROUND: Efficient pain management is one of the most important components of care in the field of emergency medicine. OBJECTIVES: This study was conducted to compare intravenous paracetamol and intravenous morphine sulfate for acute pain reduction in patients with limb trauma. PATIENTS AND METHODS: In a randomized double-blinded clinical trial, all patients (aged 18 years and older) with acute limb trauma and a pain score of greater than 3/10 in the emergency department were recruited; they received either 1 g intravenous paracetamol or 0.1 mg/kg intravenous morphine sulfate over 15 minutes. The primary outcome was the pain score measured on a numerical rating scale at 0, 15 and 30 minutes after commencing drug administration. The requirement for rescue analgesia and the frequency of adverse reactions were also recorded. RESULTS: Sixty patients randomly received either IV paracetamol (n = 30) or IV morphine (n = 30). The mean reduction in numerical rating scale pain intensity scores at 30 minutes was 3.86 (± 1.61) for paracetamol, and 2.16 (± 1.39) for morphine. However, pain relief was significantly higher in the paracetamol group compared to the morphine group (P < 0.001). Four patients in the paracetamol group and 15 patients in the morphine group needed rescue analgesia and the difference was significant (P = 0.05). CONCLUSIONS: Intravenous paracetamol appears to provide better analgesia than intravenous morphine in acute limb trauma. Further larger studies are required.

Comparison of Toxicity of CdSe: ZnS Quantum Dots on Male Reproductive System in Different Stages of Development in Mice.

BACKGROUND: Quantum dots (QDs) are new types of fluorescent materials for biological labeling. QDs toxicity study is an essential requirement for future clinical applications. Therefore, this study aimed to evaluate cytotoxic effects of CdSe: ZnS QDs on male reproductive system. MATERIALS AND METHODS: In this experimental study, the different concentrations of CdSe: ZnS QDs (10, 20 and 40 mg/kg) were injected to 32 male mice (adult group) and 24 pregnant mice (embryo group) on day 8 of gestation. The histological changes of testis and epididymis were studied by a light microscopy, and the number of seminiferous tubules between two groups was compared. One-way analysis of variance (one-way Anova) using the Statistical Package for the Social Sciences (SPSS, SPSS Inc., USA) version 16 were performed for statistical analysis. RESULTS: In adult group, histological studies of testis tissues showed a high toxicity of CdSe: ZnS in 40 mg/kg dose followed by a decrease in lamina propria; destruction in interstitial tissue; deformation of seminiferous tubules; and a reduction in number of spermatogonia, spermatocytes, and spermatids. However, there was an interesting result in fetal testis development, meaning there was no significant effect on morphology and structure of the seminiferous tubules and number of sperm stem cells. Also histological study of epididymis tissues in both groups (adult and embryo groups) showed no significant effect on morphology and structure of tubule and epithelial cells, but there was a considerable reduction in number of spermatozoa in the lumen of the epididymal duct in 40 mg/kg dose of adult group. CONCLUSION: The toxicity of QDs on testicular tissue of the mice embryo and adult are different before and after puberty. Due to lack of research in this field, this study can be an introduction to evaluate the toxicity of QDs on male reproduction system in different stages of development.

The effect of aerobic exercise on hepatotoxicity induced by intratracheal instillation of iron oxide nanoparticles in Wistar rats.

Iron oxide nanoparticles (IONPs) can cause significant health problems due to their unique physicochemical properties and environmental characteristics. They are found as ultrafine particles in ambient air. After inhalation, these particles move from the lung to phagocytosis tissues, especially the liver. The aim of present study was to investigate the effect of concurrent aerobic exercise and IONPs on liver enzymes and histological hepatic appearance. 48 rats were divided into six groups: experimental 1 (aerobic exercise), experimental 2 (nanoparticle, anesthesia), experimental 3 (aerobic exercise, nanoparticles, anesthesia), placebo 4 (distilled water, anesthesia), placebo 5 (aerobic exercise, anesthesia), and control group. In groups 2 and 3, 40 mg/kg/b.w. of IONPs was injected via intratracheal installation every other day for 14 days. Groups 1, 3, and 5 [corrected] run on treadmill for 30 minutes with the intensity of 35-40% VO2max (maximal oxygen consumption) every day. ALT was increased in group 1 but decreased in groups 2 and 3. AST was not significant in any of the groups, while ALP was reduced significantly in groups 2 and 3 (p < 0.05). Histological examination of the liver showed that, in groups 2 and 3, hepatic cells were damaged and also the congestion, inflammation, mononuclear cell infiltration, and ballooning degeneration were occurred. Tissue injuries in group 3 were less than those of group 2. These findings indicated that hepatotoxicity was caused by iron oxide nanoparticles; however, low-intensity aerobic exercise could decrease the damage somewhat.

The effects of Artemisia deserti ethanolic extract on pathology and function of rat kidney.

OBJECTIVES: Medicinal plants played an important role in human health. The kidney is a major organ for elimination the additional materials of body. Some of metabolic waste products are excreted through the kidneys, give us useful information about kidney health. Therefore, the aim of this research was to study the effects of A. deserti flowering tips extract on kidney. MATERIALS AND METHODS: Three groups of animal were studied. Wistar rats were divided into three groups. Group 1 was injected with saline, group 2 and 3 were injected with extract, 100 mg/kg and 200 mg/kg, respectively. The animals were anesthetized, blood samples were collected 2 days after the last injection, then urea, uric acid and creatinine levels were assayed. Also, the kidney histology was studied. RESULTS: No significant changes in urea and uric acid were observed. But, creatinine concentration was changed significantly in group 3 compared to other groups. The extract caused histologic changes in the kidney, including, glomerular atrophy, congestion of inflammatory cells and degeneration of the renal tubules. CONCLUSION: The results showed that A. deserti extract was able to damage the kidney tissue. However, the reason for these histopathological changes remains to be clarified.

Magnetic nanoparticles supported ionic liquids improve firefly luciferase properties.

Ionic liquids as neoteric solvents, microwave irradiation, and alternative energy source are becoming as a solvent for many enzymatic reactions. We recently showed that the incubation of firefly luciferase from Photinus pyralis with various ionic liquids increased the activity and stability of luciferase. Magnetic nanoparticles supported ionic liquids have been obtained by covalent bonding of ionic liquids-silane on magnetic silica nanoparticles. In the present study, the effects of [γ-Fe2O3@SiO2][BMImCl] and [γ-Fe2O3@SiO2][BMImI] were investigated on the structural properties and function of luciferase using circular dichroism, fluorescence spectroscopy, and bioluminescence assay. Enzyme activity and structural stability increased in the presence of magnetic nanoparticles supported ionic liquids. Furthermore, the effect of ingredients which were used was not considerable on K(m) value of luciferase for adenosine-5'-triphosphate and also K(m) value for luciferin.