The induction of tau aggregation is restricted by sulfamethoxazole and provides new information regarding the use of the drug.

The aggregation of tau protein in the form of paired helical filament (PHF) leads to the breakdown of microtubule structure and the development of neurodegenerative disorders, such as Alzheimer's disease. Therefore, inhibiting tau protein aggregation is a potential strategy for preventing the progression of these disorders. In this study, sulfamethoxazole (SMZ), an antibiotic that easily crosses the blood-brain barrier and interacts with tau protein, was tested for its ability to inhibit tau aggregation in vitro. Various multi-spectroscopic techniques including XRD, LDH cytotoxicity colorimetric assay, and microscopic imaging were employed. The results showed that SMZ effectively interacts with tau protein through hydrogen and van der Waals interactions. It also effectively inhibited tau protein aggregation in vitro and significantly reduced toxicity in the SH-SY5Y neuroblastoma cell line. Molecular docking and MD simulation results suggested that SMZ may reduce tau protein aggregation by interacting with the PHF6 motif. Overall, these findings indicate that SMZ has therapeutic potential as a tau protein aggregation inhibitor, at least under in vitro conditions. These findings suggest that SMZ has potential as a treatment for neurodegenerative disorders involving tau protein aggregation. However, further research is needed to confirm these results and assess the effectiveness of SMZ in animal models and clinical trials.Communicated by Ramaswamy H. Sarma.

Identification of novel metallo-ß-lactamases inhibitors using ligand-based pharmacophore modelling and structure-based virtual screening.

Metallo-ß-lactamases (MBLs) are a group of enzymes that hydrolyze the most commonly used ß-lactam-based antibiotics, leading to the development of multi-drug resistance. The three main clinically relevant groups of these enzymes are IMP, VIM, and NDM. This study aims to introduce potent novel overlapped candidates from a ZINC database retrieved from the 200,583-member natural library against the active sites of IMP-1, VIM-2, and NDM-1 through a straightforward computational workflow using virtual screening approaches. The screening pipeline started by assessing Lipinski's rule of five (RO5), drug-likeness, and pan-assay interference compounds (PAINS) which were used to generate a pharmacophore model using D-captopril as a standard inhibitor. The process was followed by the consensus docking protocol and molecular dynamic (MD) simulation combined with the molecular mechanics Poisson-Boltzmann Surface Area (MM-PBSA) method to compute the total binding free energy and evaluate the binding characteristics. The absorption, distribution, metabolism, elimination, and toxicity (ADMET) profiles of the compounds were also analyzed, and the search space decreased to the final two inhibitory candidates for B1 subclass MBLs, which fulfilled all criteria for further experimental evaluation.Communicated by Ramaswamy H. Sarma.

Natural Immunosuppressants as a Treatment for Chronic Insomnia Targeting the Inflammatory Response Induced by NLRP3/caspase-1/IL-1ß Axis Activation: A Scooping Review.

Chronic insomnia is an inflammatory-related disease with an important pathological basis for various diseases which is a serious threat to a person's physical and mental health. So far, many hypotheses have been proposed to explain the pathogenesis of insomnia, among which inflammatory mechanisms have become the focus of scientific attention. In this regard, the aim of the present scooping review is to evaluate the potential benefits of natural compounds in treatment of chronic insomnia targeting nucleotide-binding oligomerization domain (NOD)-like receptor-pyrin-containing protein 3 (NLRP3)/caspase-1/IL-1ß axis as one of the most important activators of inflammatory cascades. The data show that compounds that have the potential to cause inflammation induce sleep disorders, and that inflammatory mediators are key molecules in regulating the sleep-related activity of neurons. In the inflammatory process of insomnia, the role of NLRP3 in the pathogenesis of insomnia has been gradually considered by researchers. NLRP3 is an intracellular sensor that recognizes the widest range of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). After identification and binding to damage factors, NLRP3 inflammasome is assembled to activate the caspase-1 and IL-1ß. Increased production and secretion of IL-1ß may be involved in central nervous system dysregulation of physiological sleep. The current scooping review reports the potential benefits of natural compounds that target NLRP3 inflammasome pathway activity and highlights the hypothesis which NLRP3 /caspase-1/IL-1ß may serve as a potential therapeutic target for managing inflammation and improving symptoms in chronic insomnia.

Synthesis, in silico, in vitro and in vivo studies of novel natural-based arylidenes curcumin as potential glycohydrolase digestive enzymes inhibitors.

Diabetes is one of the most common metabolic diseases in humans and the use of herbal medicines is of great clinical importance to inhibit carbohydrate-hydrolyzing enzymes and reduce blood glucose levels in diabetic patients. Inhibition of glycosidase activity is an effective way to treat and prevent diabetes. Therefore, in this study, curcumin-based benzaldehyde derivatives were synthesized and used as influential agents in the treatment of diabetes with inhibitory properties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Glu) and α-amylase (α-Amy) as significant therapeutic targets for reducing postprandial hyperglycemia. Overall, the findings showed that due to the specific inhibitory activity against α-Glu in comparison with α-Amy, as well as more stability and antioxidant activity than curcumin, C5 and C8 derivatives are potentially important anti-diabetic drugs, not only to decrease glycemic index but also to limit the activity of the main production pathways of reactive oxygen species (ROS) in diabetic patients.Communicated by Ramaswamy H. Sarma.

Design, synthesis, spectroscopic characterizations, antidiabetic, in silico and kinetic evaluation of novel curcumin-fused aldohexoses.

Curcumin (bis-α,ß-unsaturated ß-diketone) plays an important role in the prevention of numerous diseases, including diabetes. Curcumin, as an enzyme inhibitor, has ideal structural properties including hydrophobic nature, flexible backbone, and several available hydrogen bond (H-bond) donors and acceptors. In this study, curcumin-fused aldohexose derivatives 3(a-c) were synthesized and used as influential agents in the treatment of diabetes with inhibitory properties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Gls) and α-amylase (α-Amy) which are known to be significant therapeutic targets for the reduction of postprandial hyperglycemia. These compounds were isolated, purified, and then spectrally characterized via FT-IR, Mass, 1H, and 13C NMR, which strongly confirmed the targeted product's formation. Also, their inhibitory properties against α-Gls and α-Amy were evaluated spectroscopically. The Results indicated that all compounds strongly inhibited α-Amy and α-Gls by mixed and competitive mechanisms, respectively. The intrinsic fluorescence of α-Amy was quenched by the interaction with compounds 1 and 3b through a dynamic quenching mechanism, and the 1 and 3b/α-Amy complexes were spontaneously formed, mainly driven by the hydrophobic interaction and hydrogen bonding. Fourier transform infrared spectra (FT-IR) comprehensively verified that the binding of compounds 1 and 3b to α-Amy would change the conformation and microenvironment of α-Amy, thereby inhibiting the enzyme activity. Docking and molecular dynamics (MD) simulations showed that all compounds interacted with amino acid residues located in the active pocket site of the proteins. In vivo studies confirmed the plasma glucose diminution after the administration of compound 3b to Wistar rats. Accordingly, the results of the current work may prompt the scientific communities to investigate the possibility of compound 3b application in the clinic.

Synthesis and Potential Antidiabetic Properties of Curcumin-Based Derivatives: An In Vitro and In Silico Study of α-Glucosidase and α-Amylase Inhibition.

BACKGROUND: Over the past twenty years, the prevalence of diabetes as one of the most common metabolic diseases has become a public health problem worldwide. Blood glucose control is important in delaying the onset and progression of diabetes-related complications. α-Glycosidase (α- Glu) and α-amylase (α-Amy) are important enzymes in glucose metabolism. Diabetic control through the inhibition of carbohydrate hydrolyzing enzymes is established as an effective strategy. METHODS: In this study, curcumin-based benzaldehyde derivatives with high stability, bioavailability, and favorable efficiency were synthesized. RESULTS: The results showed that L13, L8, and L11 derivatives have the highest inhibitory effect on α-Glu with IC50 values of 18.65, 20.6, and 31.7 µM and, also L11, L13, and L8 derivatives have the highest inhibitory effect on α-Amy with IC50 value of 14.8, 21.8, and 44.9 µM respectively. Furthermore, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition. CONCLUSION: L13, compared to the other compounds, exhibited acceptable inhibitory activity against both enzymes. The L13 derivative could be an appropriate candidate for further study through the rational drug design to the exploration of a new class of powerful anti-diabetic drugs considering the antioxidant properties of the synthesized compounds. The derivative helps reduce the glycemic index and limits the activity of the major reactive oxygen species (ROS) producing pathways.

Antioxidant and glycohydrolase inhibitory behavior of curcumin-based compounds: Synthesis and evaluation of anti-diabetic properties in vitro.

Naturally occurring anti-diabetic compound curcumin can prevent diabetes complications due to antioxidant and anti-inflammatory properties as well as the attenuation of postprandial hyperglycemia. In this line, we have synthesized thirteen curcumin based derivatives (L1-L13) by multi-component reaction, characterized by IR, 1HNMR, 13C NMR, MS, elemental analysis and evaluated for possible antioxidant properties and α-glucosidase (α-Glu) and α-amylase (α-Amy) inhibitory potential. The curcumin-based pyrano[2,3-d]pyrimidine derivatives could inhibit α-Glu and α-Amy enzyme activity which showed desirable antioxidant activity. Furthermore, among the series, L5, L12, L9, L10, L8 and L11 were identified as more potent inhibitors of α-Glu enzyme than curcumin and the compounds of L12, L4, L9, L5, L10, L8, L13, and L11 were the stronger inhibitors of the α-Amy enzyme in vitro. Besides, among them, L12 had the lowest IC50 for the inhibition of both enzymes. Since strong inhibitors for pancreatic α-Amy result in the progression of severe gastrointestinal side effects, the inhibitors that show the lower α-Amy/α-Glu inhibitory ratio have attracted much attention in medicinal chemistry. Besides, considering antioxidant characteristics of synthesized compounds, the L7 derivative with the highest antioxidant activity and the lowest "α-Amy/α-Glu inhibitory" ratio could be an appropriate candidate for further study through the rational drug design to the exploration of a new class of powerful anti-diabetic drugs.

Molecular Characterization of Animal Fasciola spp. Isolates from Kermanshah, Western Iran.

BACKGROUND: We evaluated the genetic diversity of samples identified morphologically as Fasciola spp. from sheep, cattle and goat from Kermanshah Province, western Iran using PCR-RFLP method. METHODS: We used PCR-RFLP analysis of ribosomal ITS1 fragment using RsaI restriction enzyme to investigate the genetic characteristics of Fasciola species obtained from different hosts (16 sheep, 28 cattle, 4 goats). The species of Fasciola were confirmed by sequencing the 700 bp region of ribosomal ITS1 gene. RESULTS: In Kermanshah, F. hepatica was present in 96% of the samples, F. gigantica was found only in two cattle sample. No hybrid forms were detected in the present study. CONCLUSION: Our results contribute to clarify the dark spots of Fasciola genotyping in different parts of Iran.

Patient safety in tehran university of medical sciences' general hospitals, iran.

BACKGROUND: It is important to focus on creating opportunities for patients' participation at all levels of health systems in order to promote their ability to improve patient safety and quality of services. The general aim of this study was to determine patient safety level in Tehran University of Medical Sciences' (TUMS) general hospitals, Tehran, Iran from patients' perspective and to determine the contributory factors on their perspective. METHODS: This was a cross-sectional study. In the spring 2011, the list of clinical departments of the six general hospitals affiliated to TUMS was obtained through the Website of TUMS. By using stratified random sampling, the sample size was calculated 300 patients. Data were collected by using a structured questionnaire and its validity and reliability were acceptable. Descriptive statistics, linear regression and logistic regression were used for analyzing the data. RESULTS: Totally, 60% of patients were female. Patient safety was evaluated high by 60% of respondents. The unmarried or educated or employed individuals tend to score lower than others. CONCLUSION: TUMS's general hospitals are enough safe from patients' perspective, patient safety should be improved. In clinical governance, contributing patients' perspective to the improvement of patient safety reforms is critical in generating new models of good practice.