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The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy. [ABSTRACT FROM AUTHOR]

Enzymes derived from microbial sources have gained increasing popularity in industrial applications over the past decades. Despite the high production cost, alkaline proteases have wide applications in industries such as tanneries, food production, and detergents. In recent years, there has been a shift towards utilizing natural carbon sources for cultivating microorganisms and extracting proteases in order to reduce production costs. This study aimed to investigate the biochemical and kinetic properties of protease enzymes obtained from Aspergillus niger cultivated in a paper waste medium and compare with the enzyme produced in a basal medium. Glucose is a more favorable carbon source compared to cellulose, so paper waste was pretreated with cellulose-degrading bacteria to convert cellulose into smaller carbohydrates. After the growth of A. niger in basal and combinational media, the enzymatic properties were compared between the extracted enzymes by using casein as substrate. The results demonstrated that A. niger could produce protease enzymes in the paper waste medium similar to the basal medium with more than 5-fold cost saving. The specific activity of the enzymes isolated from the basal and paper waste media was calculated to be 184.95 ± 10.56 U ml−1 and 169.88 ± 11.05 U ml−1, respectively. Carbon sources did not affect the optimum pH and temperature of the protease enzyme, which were found to be 8 and 37 °C, respectively. This study provides valuable insights into the production of alkaline protease from A. niger using a combinational medium (paper waste pretreated by cellulose-degrading bacteria), offering a cost-effective approach for industrial applications. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) was detected in the throat, urine, and feces but has little evidence documented of sexual transmission. Objective: Here, we aimed to diagnose the presence of COVID-19 in vaginal fluids and menses blood. Menstrual cycle duration and sexual desire were the other aims. Materials and Methods: In this cross-sectional study, 300 individuals with clinical approval of COVID-19 infection who were referred to the Alzahra hospital of Tabriz University of Medical Sciences, Tabriz, Iran were divided into mild (n = 178, partial pressure of oxygen = 91) and severe (n = 122, partial pressure of oxygen = 91) groups, also based on clinical signs and hospitalization, from January to May 2021. Demographic characteristics, menstruation, and sexual desire of individuals were recorded in the questionnaire blood sampling was done on days 2-4 for menses, and vaginal fluid after menses for polymerase chain reaction by using a Dacron tip swab. Results: Participants were studied in the mild (mean age: 43.32 ± 7.41) and severe (mean age: 47.15 ± 6.9) groups. COVID-19 infection resulted in shortening the menstrual cycle duration in the severe group (30.15 ± 2.9 vs. 25.12 ± 2.1 days, p = 0.01). Polymerase chain reaction test for vaginal fluid and menses blood was negative for all cases. Sexual desire declined in both groups, significantly. Conclusion: This virus was not present in the menses blood and vaginal fluid of women with COVID-19 infection, which proposed a low risk of virus transmission via vaginal tracts. Severe COVID-19 infection may affect the menstrual duration. [ABSTRACT FROM AUTHOR]

Background: Ovarian hyperstimulation syndrome (OHSS) is a serious life-threatening complication of infertility treatment. Vulvar edema is a disease with various causes and frequent phenomena seen in physiological and pathologic conditions like pregnancy, inflammatory disorders, tumors, idiopathic reasons, and most importantly, in the severe form of OHSS. Case Presentation: Here, we report a 26-yr-old woman with severe OHSS, recombinant follicle-stimulating hormone therapy. 8 days later, we observed a mild and asymmetrical swelling of the vulva with severe edema in the right labia. Due to the worsening of the vulvar edema even after 15 days of conservative treatment, hand massage and compressive bandaging of the vulva were performed, which caused rapid recovery within 20 min of the case. Conclusion: Treatment with a hand massage with lubricant gel followed by compressive bandaging resolved the vulvar edema immediately; it is an easy procedure without any adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Iron oxide nanoparticles (Fe2O3-NPs) are small magnetic particles that are widely used in different aspects of biology and medicine in modern life. Fe2O3-NP accumulated in the living cells due to the absence of an active system to excrete the iron ions and damages cellular organelles by high reactivity. Methods: Herein cytotoxic effects of Fe2O3-NP with a size of 50 nm on the primary culture of neonatal rat hippocampus were investigated using 2,5-diphenyltetrazolium bromide (MTT) assay. Pathophysiological signs of Alzheimer's disease such as amyloid precursor protein (APP) expression, Aß aggregation, soluble APPa, and APPß secretion were also investigated in hippocampal cells treated with various concentrations of nanoparticle (NP) for different exposure times. Results: Our results revealed that Fe2O3-NP treatment causes oxidative stress in cells which is accompanied by upregulation of the APP and Aß in a concentration-dependent manner. NP exposure also leads to more secretion of sAPPß rather than sAPPa, leading to increased activation of ß-secretase in NP-received cells. All the harmful effects accumulate in neurons that cannot be renovated, leading to neurodegeneration in Alzheimer's disease. Conclusion: This study approved iron-based NPs could help to develop Alzheimer's and related neurological disorders and explained why some of the iron chelators have therapeutic potential in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

• RhMMP-9 was expressed and purified by using recombinant E. coli bacteria. • TRZ and PRZ inhibited MMP-9 by competitive and mixed inhibition manner, respectively. • The IC 50 values of TRZ and PRZ were obtained 10.7 µM and 12.1 µM. • TRZ and PRZ quenched the intrinsic emission of MMP-9 via the static mechanism. • The structural changes were confirmed by fluorescence and CD analysis. Matrix metaloproteinase (MMP)-9, as a neuroinflammation-facilitating element, plays a significant role in neurodegenerative disorders and could be considered an inflammation control target. This study is intended to survey the effects of thioridazine (TRZ) and phenothiazines (PRZ) as neuroleptic drugs on the performance of recombinant human MMP-9 (rhMMP-9) by using experimental (ultraviolet visible (UV–vis), fluorescence, synchronous fluorescence, fluorescence resonance energy transfer (FRET) spectroscopy, circular dichroism (CD), surface plasmon resonance (SPR), and theoretical techniques (molecular docking). For this purpose, rhMMP-9 was expressed and purified by utilizing recombinant E. coli bacteria. The kinetic analysis illustrated that the different concentrations of TRZ and PRZ could considerably decrease the catalytic function of rhMMP-9 through competitive and mixed inhibition mechanisms, respectively. The results illustrated the higher affinity of TRZ-MMP-9 with an inhibitory IC 50 value of 10.7 µM in comparison with PRZ (12.1 µM) following the conformational alteration of the enzyme. In addition, hydrophobic binding and hydrogen bonds/van der Waals forces were suggested for TRZ-MMP-9 and PRZ-MMP-9, respectively. Finally, the molecular docking study demonstrated that TRZ and PRZ bind to the cavity in the catalytic and fibronectin domains, respectively, which supports the experimental data. This study provides some experimental and structural insights into the possible anti-inflammatory mechanisms of TRZ and PRZ drugs that suggest both drugs could be used as anti-MMP-9 drugs in neuroinflammatory conditions. [Display omitted] [ABSTRACT FROM AUTHOR]

A 2:1:1 MAX phase, V2AlC, composited with Al2O3 is prepared using spark plasma sintering (SPS). To obtain a sample with suitable physical and mechanical properties, an especial current rate regime is carried out for SPS. Different final temperatures of the synthesis (1000, 1200, 1400, and 1500°C) are considered (named S1000, S1200, S1400, and S1500, respectively). Phase analysis, physical and mechanical properties characterizations, and morphology of the samples are performed to determine the quality of the samples. The best characterizations belong to the samples of S1400 and S1500. Bending strengths about 325 and 316 MPa are obtained for the samples of S1400 and S1500, respectively. Regarding the total MAX phases formation and strength, the optimum sample is S1400. However, regarding bulk density, wear resistance, and hardness, S1500 has an advantage over the S1400. The advantages of S1500, as well as its larger grain size, are attributed to the better sintering of Al2O3. [ABSTRACT FROM AUTHOR]

Bacteria-derived outer membrane vesicles (OMVs) can be engineered to incorporate foreign antigens. This study explored the potential of ClearColi™-derived OMVs as a natural adjuvant and a carrier (recombinant OMVs or rOMVs) for development of an innovative therapeutic vaccine candidate harboring HIV-1 Nef and Nef-Tat antigens. Herein, the rOMVs containing CytolysinA (ClyA)-Nef and ClyA-Nef-Tat fusion proteins were isolated from ClearColi™ strain. The presence of Nef and Nef-Tat proteins on their surface (rOMV Nef and rOMV Nef-Tat) was confirmed by western blotting after proteinase K treatment. Immune responses induced by Nef and Nef-Tat proteins emulsified with Montanide® ISA720 or mixed with OMVs, and also rOMV Nef and rOMV Nef-Tat were investigated in BALB/c mice. Additionally, the potency of splenocytes exposed to single-cycle replicable (SCR) HIV-1 virions was assessed for the secretion of cytokines in vitro. Our findings showed that the rOMVs as an antigen carrier (rOMV Nef and rOMV Nef-Tat) induced higher levels of IgG2a, IFN-γ and granzyme B compared to OMVs as an adjuvant (Nef + OMV and Nef-Tat + OMV), and also Montanide® ISA720 (Nef + Montanide and Nef-Tat + Montanide). Moreover, IFN-γ level in splenocytes isolated from mice immunized with rOMV Nef-Tat was higher than other regimens after exposure to SCR virions. Generally, ClearColi™-derived rOMVs can serve as potent carriers for developing effective vaccines against HIV-1 infection. • Conferring advantage in stimulation of immune responses by linkage of Nef antigen to Tat. • Inducing Th1 and Th2-skewed immunity by Montanide® and Clearcoli™ OMV, respectively as an adjuvant. • Observing the highest secretion of humoral and cellular immunity by rOMV Nef and rOMV Nef-Tat. • Eliciting significantly more total IgG, IgG2a, IFN-γ and Granzyme B by rOMV Nef-Tat than rOMV Nef. • Higher IFN-γ by rOMV Nef-Tat -immunized mice after exposure to SCR virions than other regimens. [ABSTRACT FROM AUTHOR]

Despite the regulatory role of Tau protein in the stabilization and assembly of microtubules, this protein has an important function in the protection and stabilizing of DNA molecules in the cell nucleus. In the present study, it has been indicated that glycation of lysine residues (Lys-267, Lys-274, and Lys-280) in the microtubule-binding domain (MBD) can considerably decrease its binding affinity to DNA molecules. The structural analysis also confirmed that the decreased glycated tau-DNA complex's stability was due to structural modification of this protein after the glycation process. The study of hippocampal cells under hyperglycemic conditions showed that near to 70% of Tau proteins glycated in these cells, although the expression of Tau remained unaffected. The assessment of H3K9me2, as a marker for binding of Tau to pericentromeric heterochromatin (PCH), indicated that localization of Tau protein on PCH was remarkably decreased at high glucose conditions relative to the controls. It is suggested that increasing the structural stability of Tau protein limits the ability of this protein for DNA binding, while the molecular and physical barrier of glycated Lys residues should not be neglected. [ABSTRACT FROM AUTHOR]

Background: Advanced age is associated with a decline in the natural oocytes, low oocyte yield, and also increases the assisted reproductive technology (ART) failure rate, and consequently resulted in a pregnancy rate decrease. Platelet-rich plasma (PRP) is one of the proposed therapeutic strategies for women with poor ovarian response (POR). Because of the autologous source of PRP, the lowest risks of disease transmission, immunogenic and allergic reactions have been expected. This study aimed to evaluate the single-dose intraovarian injection of autologous PRP in poor ovarian reserve. Materials and Methods: We conducted a clinical trial study in the Al-Zahra hospital and Milad Infertility Clinic, Tabriz, Iran (April and May, 2021). A total of thirty-five women with a POR and mean age 40.68 ± 0.34 enrolled in this study. After injection of autologous PRP into the ovaries, the number of oocytes, antral follicles, and level of estradiol, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteal hormone (LH), FSH/LH ratio also were evaluated while, these parameters were evaluated before PRP administration. Results: At the 2-month follow-up, women treated with PRP showed a significant elevation in the number of oocytes (3.68 ± 0.24, P=0.0043) and embryos (3.17 ± 0.14, P=0.0001), as well as in the estradiol levels (404.1 ± 16.76 vs. 237.7 ± 13.14, P=0.0003). Conclusion: Single PRP injection is effective and might be a promising therapeutic approach in the patients with POR to conceive with their own oocytes, although further evidence is required to assess the influence of PRP on the live birth rate. [ABSTRACT FROM AUTHOR]

Objective: Sustained inflammation, which could be promoted by Aß aggregation and tau hyperphosphorylation, is a critical player in Alzheimer's disease (AD) pathogenesis. In the first phase, this study was designed to evaluate the anti-inflammatory properties of Ecballium elaterium (EE), as a Mediterranean therapeutic plant, and its effects on biochemical and behavioral signs of nucleus basalis of Meynert lesioned (NBML) rats, as an approved model of AD. In the second phase, we investigated the effect of EE on nuclear factor (NF)-κB pathway which is responsible for encoding proteins involved in the inflammatory cascade. Materials and Methods: Animals were divided randomly into four groups as following: control, NBML rats (AD), AD rats that were treated by high- and low-dose EE. Prostaglandins (PGs) levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Cyclooxygenase-2 (COX-2) and acetylcholinesterase (AChE) levels were assessed by fluorometric kit and Elman method, respectively. Behavioral signs were evaluated by Morris Water Maze (MWM) test and inflammatory proteins content was analyzed by immunoblotting method. Results: According to the results, treatment of NBML rats with EE fruit juice reduced PGs and cytokines more than 2-fold in comparison with AD rats through inhibition of COX-2 enzyme. Attenuation of inflammatory response in NBML rats was accompanied by reduced AChE activity (about 3-fold) and improved learning ability. Interestingly, EE reduced NF-κB expression for about 3-fold which resulted in a more than 10-fold increase in IκBa/P-IκBa ratio. Conclusion: Our results confirmed the TNF-a/cytokines/NF-κB/COX-2 pathway involves as the main inflammatory response in NBML rats. We also provided biochemical and behavioral evidence which introduces EE as an anti-inflammatory adjuvant to improve pathophysiological signs in patients suffering from AD and related dementia. [ABSTRACT FROM AUTHOR]

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca2+ homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments. [ABSTRACT FROM AUTHOR]

Donepezil (DPZ) is a well-known drug for Alzheimer's disease that inhibits acetylcholinesterase activity (AChE). In the present study, the inhibitory effect of DPZ on non-enzymatic glycated-AChE (GLY-AChE) was studied by different experimental and simulation techniques. The initial investigation revealed that glycation process could reduce AChE activity approximately 60% in the pure enzyme and 38% in the extracted crude AChE from neural cells cultured in the presence of high glucose (HG) concentration. It is suggested that glycation of lysine residues on the structure of AChE could change the conformation of the active site (Trp-86 and His-447) in a way that the orientation of acetylcholine interrupted. The further studies indicated that DPZ is although a strong inhibitor for the native enzyme, it is not able to affect the GLY-AChE activity. The K D values of AChE-DPZ and GLY-AChE-DPZ complexes were estimated to be 1.88 × 10−9 and 2.10 × 10−6, respectively. The stability assessment showed that AChE-DPZ complex is more stable than the glycated complex. Our results indicate that, glycation process could impact on the conformation of the residues involved in the DPZ binding cavity on α-helix domain. Therefore, DPZ is not able to bind its specific cavity to induce its inhibitory effects on GLY-AChE. [ABSTRACT FROM AUTHOR]

Objectives: Uncontrolled cell proliferation was caused by multiple deficient pathways that inhibition of one pathway may result to activate an alternative pathway. Therefore, combination of drugs which targeted multiple pathways could be beneficial to overcome drug resistance. Ciprofloxacin (CPF) cytotoxicity was widely investigated on cancer cell lines, and results revealed hepatoma‐derived Hep G2 cells are relatively resistant. So, this study aimed to increase CPF cytotoxicity by rational design of a supplement which targeted Ca2+ homoeostasis as major hub in unchecked proliferation. Methods: Cells were treated by CPF and/or pilocarpine (PILO), and cell cycle distribution, caspases activity and regulatory proteins were evaluated. Key findings: MTT and flow cytometry analysis confirmed administration of CPF + PILO causes more cytotoxicity. CPF‐exposed cells accumulated in S phase due to DNA damages while PILO + CPF imposed G0 stage arrest through cyclin D1 and P‐Akt downregulation. Caspase 8 was activated in cells treated by CPF but accompaniment of PILO with CPF led to activation of caspase 9, 8 and 3 and ROS overproduction. Conclusions: Ciprofloxacin imposed mitochondrial‐independent apoptosis while PILO + CPF caused mitochondrial‐dependent and independent apoptosis simultaneously. Consequently, coadministration of PILO and CPF causes intense cytotoxic effects through targeting the mitochondria, DNA gyrase enzyme and other unknown mechanisms. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an advanced neurodegenerative disorder greatly accompanied by cognitive deficits, oxidative stress, inflammation, amyloid plaques deposition, and acetylcholinesterase (AChE) hyper-activation. Growing evidence suggests natural compounds with antioxidant and anti-inflammatory features improve pathophysiological signs of AD. The present study was designed to investigate the effects of Delphinidin (25, 50 mg/kg) as an anthocyanidin on spatial memory impairment and AD hallmarks such as hippocampal AChE activity, amyloid plaques deposition, oxidative stress and expression of amyloid precursor protein (APP), AChE, and amyloid beta (Aβ) proteins in nucleus basalis of Meynert (NBM) lesioned rats as the most prevalent animal model of AD. Interestingly, Delphinidin-treated animals showed a significant decrease in escape latency and distance moved. Furthermore, in probe test, NBM lesioned rats treated with both doses of Delphinidin spent more time in the target quadrant zone in Morris water maze task. It could also interact with catalytic site of AChE enzyme and inhibits acetylcholine hydrolysis in in vitro and in vivo conditions. In addition, Delphinidin could scavenge additional produced reactive oxygen molecules dose dependently. Our immunoblotting analysis confirmed high dose of Delphinidin reduced AChE, APP and Aβ contents in AD model. Staining of hippocampus tissue revealed that Delphinidin treatment decreased amyloid plaques formation in NBM lesion rats. It seems that Delphinidin is a plate-like molecule intercalated between β-plated sheets related to Aβ molecules and inhibited amyloid fibril formation. Altogether, Delphinidin and Delphinidin-rich fruits could be suggested as a therapeutic adjuvant in AD and other related cognitive disorders. [ABSTRACT FROM AUTHOR]

Outer membrane vesicles (OMVs) are spherical nanoparticles released from gram-negative bacteria. OMVs were originally classified into native 'nOMVs' (produced naturally from budding of bacteria) and non-native (produced by mechanical means). nOMVs and detergent (dOMVs) are isolated from cell supernatant without any detergent cell disruption techniques and through detergent extraction, respectively. Growth stages and conditions e.g. different stress factors, including temperature, nutrition deficiency, and exposure to hazardous chemical agents can affect the yield of OMVs production and OMVs content. Because of the presence of bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins and the vesicle structure, OMVs have been developed in many biomedical applications. OMVs due to their size can be phagocytized by APCs, enter lymph vessels, transport antigens efficiently, and induce both T and B cells immune responses. Non-engineered OMVs have been frequently used as vaccines against different bacterial and viral infections, and various cancers. OMVs can also be used in combination with different antigens as an attractive vaccine adjuvant. Indeed, foreign antigens from target microorganisms can be trapped in the lumen of nonpathogenic vesicles or can be displayed on the surface through bacterial membrane protein to increase the immunogenicity of the antigens. In this review, different factors affecting OMV production including time of cultivation, growth media, stress conditions and genetic manipulations to enhance vesiculation will be described. Furthermore, recent advances in various biological applications of OMVs such as vaccine, drug delivery, cancer therapy, and enzyme carrier are discussed. Generally, the application of OMVs as vaccine carrier in three categories (i.e., non-engineered OMVs, OMVs as an adjuvant, recombinant OMVs (rOMVs)), as delivery system for small interfering RNA and therapeutic agents, and as enzymes carrier will be discussed. • Describing non-engineered OMV-based vaccines for different bacterial infections. • Explaining the role of OMVs as an attractive adjuvant for vaccine development. • Application of OMVs in combination with different adjuvants to enhance immunity. • Discussing the role pf ClyA and Hbp for rOMVs construction. • Delivering proteins, small interfering RNA, drugs, and enzymes by OMVs. [ABSTRACT FROM AUTHOR]

The hippocampus is a part of the brain's medial temporal lobe that is located under the cortex. It belongs to the limbic system and helps to collect and transfer information from short-term to long-term memory, as well as spatial orientation in each mammalian brain hemisphere. After more than two centuries of research in brain asymmetry, the hippocampus has attracted much attention in the study of brain lateralization. The hippocampus is very important in cognitive disorders, related to seizures and dementia, such as epilepsy and Alzheimer's disease. In addition, the motivation to study the hippocampus has increased significantly due to the asymmetry in the activity of the left and right hippocampi in healthy people, and its disruption during some neurological diseases. After a general review of the hippocampal structure and its importance in related diseases, the asymmetry in the brain with a focus on the hippocampus during the growth and maturation of healthy people, as well as the differences created in patients at the molecular, functional, and physiological levels are discussed. Most previous work indicates that the hippocampus is lateralized in healthy people. Also, lateralization at different levels remarkably changes in patients, and it appears that the most complex cognitive disorder is caused by a new dominant asymmetric system. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose Phenytoin is a major anticonvulsant drug that is effective to improve arrhythmia and neuropathic pain. According to early works, phenytoin affected cell membrane depolarization by sodium channel blocking, guanylyl and adenylyl cyclase suppression that cause to intracellular Na+ and Ca2+ downregulation. This study was aimed to clarify some ambiguities in pathophysiological action of phenytoin by in vitro and molecular docking analyses. Methods In this study intracellular free Ca2+ of primary culture of embryonic mouse hippocampus evaluated via Fura 2 as fluorescent probe. The effects of phenytoin on ADP ribosyl cyclase activity was assessed by recently developed fluorometric assay. Molecular docking simulation was also implemented to investigate the possible interaction between phenytoin and CD38. Results Our results confirmed phenytoin competitively inhibits cyclase activity of CD38 (IC50= 8.1 µM) and reduces cADPR content. cADPR is a Ca2+-mobilising second messenger which binds to L-type calcium channel and ryanodine receptors in cell and ER membrane and increases cytosolic free Ca2+. Ca2+ content of cells decreased significantly in the presence of phenytoin in a dose dependent manner (IC50 = 12.74 µM). Based on molecular docking analysis, phenytoin binds to deeper site of CD38 active site, mainly via hydrophobic interactions and consequently inhibits proper contact of substrate with catalytic residues specially Glu 226, Trp 186, Thr221. Conclusion Taken together, one of the anticonvulsant mechanisms of phenytoin is Ca2+ inhibition from CD38 pathway, therefore could be used in disorders that accompanied by CD38 over production or activation such as heart disease, depression, brain sepsis, airway disease, oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Purpose: Manganism is a cognitive disorder take places in peoples are exposed to environmental manganese pollution. Overexposure to manganese ion (Mn2+) mainly influences central nervous system and causes symptoms that increase possibility of hippocampal damages. Methods: In this study rats were administrated by two different doses of MnCl2 and behavioral and physiological consequences were evaluated. We also investigated effects of E. Amoenum on Mn2+-imposed toxicity by behavioral, biochemical, immunoblotting and histological studies on hippocampus tissue. Results: Results showed metal overexposure increases oxidative stress mainly by lipid peroxidation and reactive oxygen species overproduction. Histological studies and caspase 3 analyses by immunoblotting revealed Mn2+ induced apoptosis from mitochondrial-dependent pathway in the presence of low metal dose. This study provides evidence that oral administration of E. amoenum extract inhibited manganese neurotoxicity by oxidative stress attenuation and apoptosis reduction that lead to improved depression like behavior. Plant extract also increased catecholamine content in Mn2+ treated hippocampus. Conclusion: As molecular and pathophysiological effects of E. amoenum, it could be considered as a pre-treatment for Parkinson and Parkinson like disorders in high-risk people. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder greatly accompanied by oxidative stress and acetylcholine reduction in synaptic cleft that leads to dementia. Previously approved there is correlation between nucleus basalis of Meynert (NBM) degeneration and loss of memory, learning ability and thought. The aim of this study was to investigate improving effects of Echium amoenum aqueous extract on memory deficient, pathophysiological and oxidative damages imposed by NBM lesion in rats as documented AD model. Results showed NBM destruction causes hash oxidative stress that possibly leads to neurodegeneration in hippocampus tissue. Orally administration of plant extract significantly reduced oxidative stress by reactive molecules scavenging that resulted to decrease lipid peroxidation also. Plant extract treatment inhibited acetylcholine esterase enzyme (more than 5 folds) in hippocampus tissue related to NBM lesioned rats. Histological studies approved NBM lesion causes harsh neurodegeneration in hippocampus tissue possibly by acetylcholine reduction that was compensated by plant extract protective effects. Interestingly improving effects of plant in molecular level causes improved spatial learning ability in Morris water maze test. By considering pathophysiological and molecular similarities between AD and NBM lesion model, E. amoenum could be used as a therapeutic adjuvant in patients suffering from Alzheimer or similar cognitive disorders. [ABSTRACT FROM AUTHOR]

Molecular markers within or close to genes of interest play essential roles in marker-assisted selection. PCRbased markers have been developed for numerous traits in different plant species including several genes conferring resistance to viruses in potato. In the present work, rapid and reliable approaches were developed for the simultaneous detection of Ryadg and Ry-fsto, Ns, and PLRV.1 genes conferring resistance to Potato virus Y, Potato virus S and Potato leafroll virus, respectively, on the basis of previously published and newly modified markers. The sequence characterized amplified region (SCAR) markers for Ryadg, Ns and PLRV1 and the newly modified cleaved amplified polymorphic sequences (CAPS) marker for Ry-fsto were amplified in one PCR reaction which could simply characterize Ryadg and PLRV.1 resistance. Additional digestion of amplicons with EcoRV and MfeI for genotyping the Ry-fsto and Ns resistance genes, respectively, was needed. The effectiveness of genotyping in triplex and tetraplex PCRs was tested on 35 potato varieties used for potato seed production and breeding programs. [ABSTRACT FROM AUTHOR]

There is a paucity of research on medication de-prescribing. Currently, the field of child psychiatry offers more evidence on how to start children and adolescents on medication than on how long to treat them, and how to best discontinue the medication. Evidence-based and clinically rooted treatment plans for how to discontinue medicine are just as important to develop as effective treatment plans in how to start medicine. This article serves to provide some guiding principles in the appropriate and safe discontinuation of psychotropic medicines for children and adolescents. [ABSTRACT FROM AUTHOR]

The hippocampus is a complex brain structure and undergoes severe sclerosis and gliosis in temporal lobe epilepsy (TLE) as the most common type of epilepsy. The key features of the TLE may be reported in chronic animal models of epilepsy, such as pilocarpine model. Therefore, the current study was conducted in a rat pilocarpine model of acquired epilepsy. Two-dimensional gel electrophoresis based proteomic technique was used to compare the proteome map of the left and right hippocampus in both control and epileptic rats. Generally, 95 differentially expressed spots out of 1300 spots were identified in the hippocampus proteome using MALDI-TOF-TOF/MS. Within identified proteins, some showed asymmetric expression related to the mechanisms underlying TLE imposed by pilocarpine. Assessment of lateralization at the molecular level demonstrated that expression of proteins involved in dopamine synthesis was significantly more in the right hippocampus than the left one. In the epileptic model, reduction in dopamine pathway proteins was accompanied by an increase in the expression of proteins involved in polyamine synthesis, referring to a new regulating mechanism. Our results revealed changes in the laterality of protein expression due to pilocarpine-induced status epilepticus that could present some new proteins as potential candidates for antiepileptic drug design. Biological significance In the current study, two-dimensional gel electrophoresis (2-DE) based proteomic technique was used to profile changes in the left and right hippocampus proteome after pilocarpine induced status epilepticus. Spots of proteome maps for two hemispheres were excised and identified with MALDI-TOF-TOF/MS. Analysis of proteome map of the left and right hippocampus revealed a lateralization at the molecular level, in which the expression of proteins involved in dopamine synthesis and release were significantly more in right hippocampi than the left ones in the normal rats. Also, the expression of proteins involved in polyamine synthesis significantly increased in epileptic hippocampus (considerably higher in right hippocampi), whilst the proteins which included in dopamine pathways were decreased. Our results revealed changes in the laterality of protein expression due to pilocarpine-induced status epilepticus that could present some new proteins as potential candidates for antiepileptic drug design. [ABSTRACT FROM AUTHOR]

Medicago sativa Linn. or alfalfa (Leguminosae) has been used traditionally as an effective cure for CNS, heart and metabolic disorders and digestive aids. Alfalfa is a resistant plant against stress due to small antioxidant molecules and enzymes. Our previous work demonstrated that 100 μg/ml of 50 nm size Fe 2 O 3 -NP causes harsh oxidative stress in HepG2 cells and 100 mg/kg of same nanoparticle causes extreme damage in rat's liver. Therefore it can be used as a useful model for invivo and invitro studies of oxidative stress. This study assessed the effects of two concentration of alfalfa on the mentioned invivo and invitro damage. Our results showed alfalfa reduced reactive oxygen species (ROS) production and enhanced reduced glutathione (GSH) that cause reduction of DNA fragmentation and prevent apoptosis pathway so improve viability of the cells. Results also showed alfalfa decreased hepatic enzymes penetrating and lipid peroxidation in rat's liver. Note that Fe 2 O 3 -NP potentially has widespread biological application but its usage is limited due to bio incompatibility. A suitable antioxidant compound that reduce nanoparticle side effects can be used as an effective adjuvant with iron oxide nanoparticle (and may be other nanomaterials) in biological applications. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson's disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat's brain by MnCl² injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days. [ABSTRACT FROM AUTHOR]

Unintended consequences of participating in research studies are not well characterized, particularly in veterans who are frequent study participants. Our objective, then, was to assess the rate of and variables associated with distress resulting from veterans' participation in a study on a sensitive subject. Veterans Administration (VA) hospital out-patients were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Distress--upset requiring clinical intervention--was assessed, as were sociodemographic characteristics, post-traumatic stress disorder (PTSD), depression, and locus of control (LOC). Three hundred fifty-one veterans participated. Forty-three (12%) became distressed. Modeling indicated distress was associated with minority status (odds ratio [OR] -- 5.72, 95% confidence interval [CI] = 1.59, 20.58), PTSD (OR = 2.66, 95% CI -- 1.12, 6.29), and external LOC (OR = 6.27, 95% CI = 2.82, 13.90). Distress related to study participation was high in this veteran sample. Higher rates in some subgroups suggested that some individuals may not be able to accurately anticipate risk for harm in sensitive studies. [ABSTRACT FROM AUTHOR]

Protein-protein interactions are involved in many biological processes and cellular functions and they are interesting therapeutic targets is several diseases for drug design and development. In the present study, the possible effects of caffeine (CF) as mostly consumed psychoactive substances in the modern life on tau-tau interactions were studied by localized surface plasmon resonance (LSPR) method. The obtained data indicated that tau monomers have high affinity to bind to the immobilized tau proteins on the surface of LSPR sensor chip of the gold nanoparticles (LSPR-AuNPs) and the LSPR peak was red-shifted from 598 ± 1.5 nm to 629 ± 0.1 nm. However, it was shown that the binding affinity of CF-tau complex was remarkably reduced. These results revealed that the binding of CF molecules on free tau monomers could potentially interrupt the interaction of tau-tau proteins. Circular dichroism (CD) and FTIR spectroscopy was applied to analyze the secondary structure of tau protein in the absence or presence of different amounts of CF. The results showed that CF can induce more random coil structure to the protein and also increase its structural stability. Docking studies and molecular dynamics simulations elucidated that CF not only can possibly provide a molecular and physical barrier for tau-tau interaction by binding to the microtubule binding domain, but also it decreases the stability of tau dimer, which were supported by experimental data. [Display omitted] • Tau proteins were immobilized covalently on the surface of LSPR sensor chip of the gold nanoparticles (LSPR-AuNPs). • Caffeine (CF) can reduce the binding affinity of tau monomers to the immobilized tau proteins on the surface of LSPR-AuNPs. • CF molecules could potentially interrupt the interaction of tau-tau proteins. • CF is able to induce more random coil on the secondary structure of tau protein and also increase its structural stability. [ABSTRACT FROM AUTHOR]

In the present work, physio-biochemical and DNA methylation analysis were conducted in wheat (Triticum aestivum L.) cultivars "Bolani" (drought-tolerant) and "Sistan" (drought-sensitive) during drought treatments: well-watered (at 90% field capacity (FC)), mild stress (at 50% FC, and severe stress (at 25% FC). During severe stress, O 2 •− and H 2 O 2 content in cultivar Sistan showed significant increase (by 1.3 and 2.5-fold, respectively) relative to cultivar Bolani. In Bolani, the increased levels of radical scavenging activity (by 32%), glycine betaine (GB) (by 11.44%), proline (4-fold), abscisic acid (by 63.76%), and more stability of relative water content (RWC) (2-fold) were observed against drought-induced oxidative stress. Methylation level significantly decreased from 70.26% to 60.64% in Bolani and from 69.06% to 59.85% in Sistan during stress, and higher decreased tendency was related to CG and CHG in Bolani but CG in Sistan under severe stress. Methylation patterns showed that the highest polymorphism in Bolani was mainly as CG. As the intensity of stress increased, the enhanced physio-biochemical responses of Bolani cultivar were accompanied by a more decrease in the number of unchanged bands. According to heat map analysis, the highest difference (84.38%) in methylation patterns was observed between control and severe stress. Multivariate analysis using principal component analysis (PCA) showed a cultivar-specific methylation during stress and that methylation changes between cultivars are much higher than that of within a cultivar. Higher methylation to demethylation in Bolani (30.06 vs. 22.12%) compared to that of cultivar Sistan (23.21 vs. 30.15%) indicated more demethylation did not induce tolerance responses in Sistan. Sequencing differentially methylated fragments along with qRT-PCR analysis showed the efficient role of various DNA fragments, including demethylated fragments such as phosphoenol pyruvate carboxylase (PEPC), beta-glucosidase (BGlu), glycosyltransferase (GT), glutathione S-transferase (GST) and lysine demethylase (LSD) genes and methylated fragments like ubiquitin E2 enzyme genes in the development of drought tolerance. These results suggested the specific roles of DNA methylation in development of drought tolerance in wheat landrace. • DNA methylation links drought tolerance of wheat to metabolic acclimation. • During drought, methylation levels of Bolani outpaced demethylation and in Sistan the opposite happens. • The decreased tendency in methylation level was higher under severe stress compared to mild stress. • Drought tolerance was related to DNA methylation inducing positive/negative regulation of genes transcriptional activity. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is the key enzyme for the virus gene replication and the most important target for antiviral therapy. Toxicity, drug resistance and side effects have led to search for new antiviral agents. Farnesiferol C (FC) is a well-known biologically active sesquiterpene coumarin derivative from genus Ferula. The current study was designed to examine the impacts of FC on the structure and function of HIV-1 RT, using some theoretical and experimental methods. FC inhibited HIV-1RT activity via mixed inhibition mechanism (IC 50 = 30 μM). Spectroscopic data showed some conformational changes in the secondary as well as tertiary structure of HIV-1RT following the interaction with FC. Results showed that FC could quench the intrinsic fluorescence emission of HIV-1RT through static quenching mechanism. Thermodynamic parameters revealed that hydrogen bondings and van der Waals forces are the major forces in the binding reaction and the low equilibrium constants (K D) value obtained from surface plasmon resonance data, confirmed the high affinity of FC for HIV-1RT. Molecular docking studies indicated that FC interacts with enzyme through hydrophobic pocket. Taken together, the outcomes of this research revealed that, sesquiterpene coumarines can be used to design natural remedies as anti-HIV agents. [ABSTRACT FROM AUTHOR]

This study tested whether gradually increasing whole red or white wheat in menu items enhanced consumption by school-aged children. Whole red or white wheat content of buns and rolls served twice weekly in two suburban schools was increased over the school year from 0% to 91% in 16 and 7 incremental steps for red and white wheat, respectively. Levels of whole wheat were determined based on difference-threshold tests with a panel of trained judges. Consumption as measured by plate waste on a school-wide basis did not differ statistically from the 0% level of whole wheat until reaching the 91% level for red and 67.5% level for white wheat (a drop from ∼74% to ∼ 57% consumption). Consumption of buns and rolls regardless of wheat type or level varied with the type of accompanying menu items. Taste ratings for a subsample of ∼90 children in grades 3-6 at each school dropped slightly from the beginning to end of the school year for whole red wheat samples while ratings for whole white wheat samples did not change. A survey conducted with another subsample of 96 children in grades 4-6 in one school showed that most children had positive beliefs about health benefits of whole grain foods, liked whole grain foods and felt somewhat sure they could eat these foods in difficult situations. A gradual increase in whole wheat content in menu items resulted in favorable consumption by children. This project was funded by NIDDK and ConAgra Foods. [ABSTRACT FROM AUTHOR]

• Criteria A and B of AMPD are strongly correlated in the non-Western samples. • Five-factor frameworks of personality/temperament significantly predict Criterion A. • Criterion A is more strongly predicted by Criterion B than other personality frameworks. • Psychoticism is the strongest predictor of both intrapersonal and interpersonal functioning. We aimed to understand which of the three personality frameworks including Criterion B of the DSM-5 model, Five-Factor Model (FFM), and affective temperaments was most overlapping with both intrapersonal and interpersonal dysfunctions (Criterion A). This cross-sectional study consisted of N = 496 people from western Iran. Pearson correlation and regression techniques were used for data analysis. Although all dimensional personality frameworks were related to both personality dysfunctions, Criterion B was a stronger predictor above and beyond the other frameworks. Our findings do not support the replacement of Criterion B by traditional personality and temperament constructs. The significant incremental validity of both the FFM and affective temperaments beyond the DSM-5 model addresses potential complementary constructs to enhance Criterion B to explain Criterion A. [ABSTRACT FROM AUTHOR]

Scheme: representation of the optical sensor (SPR) fabrication process for the recognition of interaction between AChE and PPZ/TRZ. [Display omitted] • Acetylcholinesterase (AChE) is a therapeutic target for Alzheimer's disease. • The binding of PPZ/TRZ-AChE was studied using SPR and molecular docking methods. • SPR data demonstrated a higher affinity of TRZ towards AChE in comparison with PPZ. • Thermodynamic data showed that hydrogen and hydrophobic bonds were dominant. • The molecular docking results were in agreement with the experimental results. Alzheimer's disease (AD) causes dementia in most elderly individuals with cognitive and behavioral problems due to cholinergic synapse dysfunction. Thioridazine (TRZ) and perphenazine (PPZ) likely affect the acetylcholine (ACh) receptor and acetylcholinesterase (AChE) in the central nervous system (CNS) and improve the cholinergic system. This study aimed to determine the inhibitory effects of TRZ and PPZ on AChE using surface plasmon resonance (SPR) and molecular docking techniques to gain insight into the possible interaction mechanism between these medications and the enzyme. The SPR results indicated a high affinity of TRZ/PPZ to AChE (K D < 1 × 10−6 M). According to SPR results, increasing temperature decreases PPZ's binding strength to AChE while increasing the affinity of TRZ. Thermodynamic parameters demonstrated that hydrophobic interactions and hydrogen bonding are the main intermolecular forces between TRZ/PPZ and AChE. The results of the docking analysis were in good agreement with the experimental data, confirming only one binding site on AChE for TRZ and PPZ. PPZ showed a strong attachment to AChE due to its large negative binding energy (−10.58 kcal/mol). PPZ showed lower IC 50 values toward AChE and TRZ, indicating a greater inhibitory effect on AChE. [ABSTRACT FROM AUTHOR]

The present study investigates the in vitro and in vivo effect of acacetin (4'-methoxy-5,7-dihydroxyflavone) on chronic lymphocytic leukemia (CLL) B-lymphocytes and mitochondria. CLL B-lymphocytes and healthy B-lymphocytes were obtained from CLL patients and healthy donors, respectively. Mitochondria were isolated from B-lymphocytes of both groups. Xenografts in severe combined immune deficient mice were used to examine the toxicity and anti CLL activity of acacetin. We evaluated and compared the mechanism of action of acacetin on CLL and healthy B-lymphocytes and their mitochondria. We have found that acacetin (10 μM) can selectively induce apoptosis on CLL B-lymphocyte (25% at 24 h) by directly targeting mitochondria, through increased reactive oxygen species (ROS) formation, MMP collapse, MPT, release of cytochrome c, caspase 3 activation, and finally apoptosis, while sparing normal healthy B-lymphocytes unaffected at similar concentrations. Besides, oral administration of acacetin showed a potent in vivo anticancer activity in CLL xenograft mouse models. Our in vivo findings indicate that acacetin accumulates and kills CLL B-lymphocyte in a rather selective way through targeting cancerous mitochondria and ROS formation, which ends in CLL therapy. Finally, we can recommend acacetin as a promising compound for further drug development assays for the CLL treatment. [ABSTRACT FROM PUBLISHER]

Human serum albumin (HSA) shows the sequence homology and structural similarity with bovine serum albumin (BSA). Therefore, here, the interaction of natural phenolic antioxidants, ellagic acid (ELA), and its derivatives–urolithins A (ULA) and B (ULB)–with BSA was investigated. The results of surface plasmon resonance (SPR) indicated a high affinity of ELA, ULA, and ULB to BSA, with K D value < 1 × 10−6 M. The K D values of binding of the studied compounds to BSA increased with temperature, revealing a reduction in affinity with an increase in temperature. Fluorescence data showed that the quenching of BSA by tested compounds occurred via a static quenching. However, the affinity of ELA for BSA was higher than that of ULA and ULB, which may be because of the presence of a large number of hydroxyl groups in its structure. The assessment of the antioxidant activity of BSA and BSA–ELA/ULA/ULB complexes using the DPPH assay indicated that the DPPH scavenging activity of BSA increased after complex formation with ELA/ULA/ULB in the following order: BSA–ELA > BSA-ULA > BSA-ULB > BSA, which was due to their structural differences. The results of the docking analysis were in agreement with the experimental results. [Display omitted] • Binding of ellagic acid and its derivatives (urolithins A and B) to bovine serum albumin (BSA) was investigated. • Fluorescence spectroscopic data revealed the static mode of quenching. • The thermodynamic parameter suggested that the van der Waals forces and hydrogen bonds were dominant. • Molecular docking studies were in good agreement with experimental analysis. [ABSTRACT FROM AUTHOR]

We assessed detainee abuse acceptance and variables associated with it, Outpatients from a veterans' hospital were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Three questionnaire versions differed in the final line of each version's scenarios, describing abuse either as: soldier initiated, superior ordered, or wrong by a "whistleblower" soldier. Three hundred fifty-one veterans participated, 80% with service during the Vietnam War. Zero tolerance for abuse--"completely unacceptable" regardless of who the detainee was--increased with abuse severity (16% for exposure, 31% for humiliation, and 48% for rape of detainee) and with soldier initiation. The strongest, most consistently significant odds were of depressed veterans, veterans with comorbid depression/post-traumatic stress disorder, and men being approximately 2, 3, and 4 to 20 times more tolerant of abuse than those without depression/post-traumatic stress disorder and women, respectively. There may be potential value to using similar scenario-based questionnaires to study active duty military perceptions of detainee abuse. Results may inform prevention policies. [ABSTRACT FROM AUTHOR]

Objectives: The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count <100 cells/mm3 and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. Methods: This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count <100 cells/mm3, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). Results: Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (p value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (p < 0.02). Conclusions: We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count <100 mm3/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD. [ABSTRACT FROM AUTHOR]

In the present study the binding of diversin (DIV), a prenylated coumarin isolated from Ferula diversivittata , to bovine serum albumin (BSA) was investigated using surface plasmon resonance (SPR), spectrofluorimetry, and molecular docking approaches. Following the activation of carboxylic groups, via NHS/EDC, BSA was immobilized on the carboxymethyl dextran (CMD) hydrogel coated Au sensor, and was used for real-time monitoring of the interactions between DIV and BSA. K D value of DIV binding to BSA increased with increasing temperature, confirmed that the affinity between BSA and DIV decreases with rising temperature. In addition, the fluorescence and synchronous fluorescence spectroscopic data revealed that the intrinsic emission intensity of BSA was quenched via a dynamic mechanism. In addition, the micro-region around BSA tyrosine residue was changed upon interaction with DIV. The thermodynamic parameter findings suggested that the hydrophobic interactions were dominant in the binding and formation of the BSA and DIV complex. The molecular docking outputs indicated that there is only one binding site on BSA for DIV, in agreement with experimental data, and DIV bind BSA in subdomain IB. Unlabelled Image • The interaction of diversin-BSA was investigated using various spectroscopic methods. • Surface plasmon resonance data revealed interaction between BSA and diversin. • Fluorescence spectroscopic data revealed the dynamic mode of quenching. • The thermodynamic parameter suggested that the hydrophobic interactions were dominant. [ABSTRACT FROM AUTHOR]

Abstract: CuS (CS) and Cu1‐xZnxS (CZS) nanoparticles (NPs) were synthesized for the first time by a hydrothermal method from decomposition of tris(thiourea) copper (I) sulphate complex with zinc nitrate hydrate for 8 hours at 140 °C. The products have been identified by using X‐Ray diffraction analysis (XRD). These XRD patterns showed that the CS and CZS nanoparticles have a well‐ordered covellite structure with high purities. Field emission scanning electron microscope (FESEM) showed that by increasing dopant concentration, the size of Cu1‐xZnxS (x=0.01, 0.05, 0.1) nanoparticles is increased. Optical properties and band gaps were calculated with diffuse reflectance spectra (DRS) and photoluminescence (Pl), so nanoparticles with high dopant concentration (x=10%) had less band gap values. In photocatalyst studies, the CZS (x=10%) species can remove 95% Methylene Blue (MB) in the presence of H2O2 under UV light in 90 minutes. Furthermore, the CZS (x=1% ‐ 10%) NPs have excellent potential to eliminate of Hep G2 cancer cells. [ABSTRACT FROM AUTHOR]

Abstract Water molecules play a vital role in efficient drug binding to its target. Thiazolidinediones (TZDs), a class of anti-diabetic drugs, are widely used for treatment of type 2 diabetes mellitus. In the present study, the possible contribution of water molecules to the binding of TZDs to catalase, a potential target in the liver, was investigated by different experimental and theoretical methods. These studies indicated that TZDs could significantly improve the catalase catalytic function with a significant contribution from water molecules. As a probe for the differential number of released water molecules during the catalase transition from E to E* states, the activity of TZDs-catalase complexes was demonstrated to be mainly dependent on water activity. However, free catalase decomposed the substrate more independently. In addition, the spectrofluorimetry studies showed that the binding of TZDs to catalase needed the release of water molecules from the enzyme's binding pocket. The thermodynamic studies indicated that the binding enthalpy and entropy of TZDs for catalase were decreased with lower water activity. The favorable process contributes to release of water molecules from the binding pocket through the formation of hydrophobic interactions between catalase and TZDs in an enthalpic manner. Molecular docking simulations confirmed that the depletion of water molecules from the binding cavity is essential for effective interactions between TZDs and catalase. Graphical abstract Image 1 Highlights • Water molecules play an essential role in the efficient binding. • The depletion of water molecules is essential for the effective binding. • Thiazolidinediones could improve catalase activity. • The hydrophobic moiety of thiazolidinediones plays main role in the binding process. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate drug resistance patterns among Iranian people living with HIV who have taken antiretroviral therapy for 9–15 months. Methods: A cross-sectional study was conducted between December 2015 and May 2016. Two hundred fifty-two blood samples were collected from all eligible HIV-infected patients at fourteen healthcare settings, located in major provinces in Iran. The samples were examined for presence of drug resistance strains and viral load level. Moreover, a phylogenetic tree, using neighbor joining, was constructed and HIV subtypes were determined. Results: The most common subtypes were CRF35-AD (47.6%) and A1 (42.8%), followed by 45_CPX (4.8%) and C (4.8%). The resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors was reported as 19.2, 19.2, and 10.3%, respectively. M184I/V mutation was the most frequent (31.6%) mutation among NRTI-based regimens. Moreover, K103E/N was the most frequent (34.2%) NNRTI mutation. Conclusions: This is the first study to illuminate the emergence of the CPX genotype among Iranian patients. The drug resistance rate of NNRTIs was similar to that of NRTIs. By assessing drug resistance, it is possible to evaluate the efficacy of treatment and patient adherence to treatment. [ABSTRACT FROM AUTHOR]

We investigated the effect of chrysin on isolated normal and chronic lymphocytic leukemia (CLL) B-lymphocytes and their isolated mitochondria. We report that a selective and significant increase in cytotoxicity, intracellular reactive oxygen species, mitochondrial membrane potential collapse, ADP/ATP ratio, caspase 3 activation and finally apoptosis in chrysin-treated CLL B- lymphocytes. Also we determined that chrysin selectively inhibits complex II and ATPases in cancerous mitochondria. In this study we proved that the ability of chrysin to promote apoptosis in CLL B-lymphocytes performed by selectively targeting of mitochondria. Our findings may provide a potential therapeutic approach for using chrysin to target mitochondria in CLL B-lymphocytes. [ABSTRACT FROM PUBLISHER]

Background: Increasing the accessibility of antiretroviral therapy (ART) has caused the emergence of drug resistance in patients receiving ART and in naïve patients. The aim of this study was to evaluate HIV subtype and drug resistance between naïve patients and ART-experienced patients. Methods: Blood samples were collected from 78 antiretroviral and naïve HIV-1 patients; antiretroviral-resistant mutations and subtyping were then determined by sequencing pol regions. Results: Phylogenetic analysis revealed that 96.1% of sequences belong to the CRF35-AD subtype. Transmitted drug resistance was determined in 14% of drug-naïve patients and 40% of ART-experienced patients. Conclusion: The findings of this study illustrated the importance of resistance testing before and during ART treatment. This study can be used to set up a best medicine strategy in Iranian guidelines. [ABSTRACT FROM AUTHOR]

The growing incidence and transmission of drug resistant HIV-1 strains due to widespread use of antiretroviral therapy (ART) can jeopardize the success of first-line ART. While there is a known moderate prevalence of transmitted drug resistance (TDR) among newly infected Iranians, no data exist about the rate of these primary resistance mutations among the ART-naïve, chronically infected individuals who are, in fact, the main candidates for ART initiation. To address this issue, we collected blood samples from 40 ART-naïve injection drug-users (IDUs) with chronic HIV-1 infection (seroconversion time ranging from 2 to 9 years) living in Sanandaj, Iran, followed by sequencing of the protease and reverse-transcriptase regions from their HIV-1 genome. Phylogenetic analyses of the sequenced regions revealed that all samples were CRF35_AD. Transmitted resistance mutations were interpreted as surveillance drug-resistant mutations (SDRMs) based on the world health organization (WHO) algorithm. The frequency of SDRMs to any class of antiretroviral drugs was 15%, which included mutations to nucleoside reverse transcriptase inhibitors (NRTIs, 10%), with M41L and M184V as the most common (5%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs, 5%), with K103N as the only detected mutation (5%). Although not in the WHO SDRMs list, several minor protease inhibitor resistant mutations listed in the International Antiviral Society-USA panel were identified, of which M36I, H69K, L89M/V/I (each one 100%) and K20R/T (92.5%) can be considered as polymorphic signatures for CRF35_AD.The relatively high rate of TDR mutations in our study raises concerns about the risk of treatment failure in chronically infected IDUs of Sanandaj city. These results suggest that routine resistance testing should be considered before the therapy initiation in this area. Additional surveillance studies are required to generalize this deduction to other cities of Iran. [ABSTRACT FROM AUTHOR]

Identification and registration of new rice varieties are very important to be free from environmental effects and using molecular markers that are more reliable. The objectives of this study were, first, the identification and distinction of 40 rice varieties consisting of local varieties of Iran, improved varieties, and IRRI varieties using PIC, and discriminating power, second, cluster analysis based on Dice similarity coefficient and UPGMA algorithm, and, third, determining the ability of microsatellite markers to separate varieties utilizing the best combination of markers. For this research, 12 microsatellite markers were used. In total, 83 polymorphic alleles (6.91 alleles per locus) were found. In addition, the variation of PIC was calculated from 0.52 to 0.9. The results of cluster analysis showed the complete discrimination of varieties from each other except for IR58025A and IR58025B. Moreover, cluster analysis could detect the most of the improved varieties from local varieties. Based on the best combination of markers analysis, five pair primers together have shown the same results of all markers for detection among all varieties. Considering the results of this research, we can propose that microsatellite markers can be used as a complementary tool for morphological characteristics in DUS tests. [ABSTRACT FROM AUTHOR]

Unintended consequences of participating in research studies are not well characterized, particularly in veterans who are frequent study participants. Our objective, then, was to assess the rate of and variables associated with distress resulting from veterans' participation in a study on a sensitive subject. Veterans Administration (VA) hospital outpatients were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Distress--upset requiring clinical intervention--was assessed, as were sociodemographic characteristics, post-traumatic stress disorder (PTSD), depression, and locus of control (LOC). Three hundred fifty-one veterans participated. Forty-three (12%) became distressed. Modeling indicated distress was associated with minority status (odds ratio [OR] = 5.72, 95% confidence interval [CI] = 1.59, 20.58), PTSD (OR = 2.66, 95% CI = 1.12, 6.29), and external LOC (OR = 6.27, 95% CI = 2.82, 13.90). Distress related to study participation was high in this veteran sample. Higher rates in some subgroups suggested that some individuals may not be able to accurately anticipate risk for harm in sensitive studies. [ABSTRACT FROM AUTHOR]

We assessed detainee abuse acceptance and variables associated with it. Outpatients from a veterans' hospital were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Three questionnaire versions differed in the final line of each version's scenarios, describing abuse either as: soldier initiated, superior ordered, or wrong by a "whistleblower" soldier. Three hundred fifty-one veterans participated, 80% with service during the Vietnam War. Zero tolerance for abuse--"completely unacceptable" regardless of who the detainee was--increased with abuse severity (16% for exposure, 31% for humiliation, and 48% for rape of detainee) and with soldier initiation. The strongest, most consistently significant odds were of depressed veterans, veterans with comorbid depression/post-traumatic stress disorder, and men being approximately 2, 3, and 4 to 20 times more tolerant of abuse than those without depression/post-traumatic stress disorder and women, respectively. There may be potential value to using similar scenario-based questionnaires to study active duty military perceptions of detainee abuse. Results may inform prevention policies. [ABSTRACT FROM AUTHOR]