Decoding the Intricacies of Statin-Associated Muscle Symptoms.

PURPOSE OF REVIEW: Hyperlipidemia is the major cardiovascular morbidity and mortality risk factor. Statins are the first-line treatment for hyperlipidemia. Statin-associated muscle symptoms (SAMS) are the main reason for the discontinuation of statins among patients. The purpose of this review is to guide clinicians to recognize the difference between self-limited and autoimmune statin myopathy in addition to the factors that potentiate them. Finally, treatment strategies will be discussed. This review mostly focuses on new data in the past 3 years. RECENT FINDINGS: Recent findings suggest that SAMS is a complex and multifactorial condition that involves mitochondrial dysfunction, oxidative stress, and immune-mediated mechanisms. Effective management of SAMS requires a thorough evaluation of the patient's symptoms, risk factors, and medication history, as well as consideration of alternative treatment options. While statins are effective in reducing the risk of cardiovascular events, their use is associated with a range of adverse effects, including SAMS.

Synthesis, Glucosidase Inhibition, and In Silico Modeling Analysis of Highly Fluorinated 2-Imino-1,3-thiazolines in Search of Potent Antidiabetic Agents.

In the present work, 2-imino-1,3-thiazolines featuring highly fluorinated fragments were synthesized through a straightforward cyclization of diversely substituted thioureas with 2-bromo-1-(4-fluorophenyl)ethan-1-one. The target compounds were obtained in good yields, and structures were established by FTIR and 1H- and 13C NMR spectroscopic methods. The in vitro biological assay revealed that all the compounds significantly obstruct the α-glucosidase. Compound 6d (3-fluoro-N-(3-(2-fluorophenyl)-4-(4-fluorophenyl)thiazol-2(3H)-ylidene)benzamide) showed the highest antidiabetic potential with an IC50 value of 1.47 ± 0.05 µM. In addition, computational analysis revealed the binding energy of -11.1 kcal/mol for 6d which was lower than the positive standard, acarbose (-7.9 kcal/mol). Several intermolecular interactions between the active site residues and 6d highlight the significance of 2-imino-1,3-thiazoline core in attaining the potent efficacy and making these compounds a valuable pharmacophore in drug discovery.

Liver-boosting potential: chicory compound-mediated silver nanoparticles for hepatoprotection-biochemical and histopathological insights.

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20 mg/kg of body weight), fourth group (CCl4+chicory) (1.75 mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35 mg/kg), sixth group (CCl4 + chicory of 3.25 mg/kg), seventh group (CCl4 +AgNPs 1.75 mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35 mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25 mg/kg of b. wt.). Blood samples were taken 24 h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25 mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

Mutational analysis of consanguineous families and their targeted therapy against dwarfism.

Dwarfism is a medical term used to describe individuals with a height-vertex measurement that falls below two standard deviations (-2SD) or the third percentile for their gender and age. Normal development of growth is a complicated dynamic procedure that depends upon the coordination of different aspects involving diet, genetics, and biological aspects like hormones in equilibrium. Any severe or acute pathologic procedure may disturb the individual's normal rate of growth. In this research, we examined four (A-D) Pakistani consanguineous families that exhibited syndromic dwarfism, which was inherited in an autosomal recessive pattern. The genomic DNA of each family member was extracted by using phenol-chloroform and Kit methods. Whole Exome Sequencing (WES) of affected family members (IV-11, III-5, IV-4 and III-13) from each group was performed at the Department of Medical Genetics, University of Antwerp, Belgium. After filtering the exome data, the mutations in PPM1F, FGFR3, ERCC2, and PCNT genes were determined by Sanger sequencing of each gene by using specific primers. Afterward, FGFR3 was found to be a suitable drug target among all the mutations to treat achondroplasia also known as disproportionate dwarfism. BioSolveIT softwares were used to discover the lead active inhibitory molecule against FGFR3. This research will not only provide short knowledge to the concerned pediatricians, researchers, and family physicians for the preliminary assessment and management of the disorder but also provide a lead inhibitor for the treatment of disproportionate dwarfism.Communicated by Ramaswamy H. Sarma.

Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways.

Ovarian cancer is the fifth leading cause of mortality and the most lethal gynecologic malignancy among females. It may arise from atypical borderline tumors (Type I) or serous tubal intraepithelial carcinoma (Type II). The diagnosis of cancer at its early stages is difficult because of non-specific symptoms, most patients are diagnosed at the advanced stage. Several drugs and therapeutic strategies are available to treat ovarian cancer such as surgery, chemotherapy, neoadjuvant therapy, and maintenance therapy. However, the cancer cells have developed resistance to a number of available therapies causing treatment failure. This emerging chemoresistance in ovarian cancer cells is becoming an obstacle due to alterations in multiple cellular processes. These processes involve altered drug target response, drug pumps, detoxification systems, lower sensitivity to apoptosis, and altered proliferation, and are responsible for developing resistance to anticancer medicines. Various research reports have evidenced that these altered processes might play a role in the emergence of resistance. This review addresses the recent advances in understanding the underlying mechanisms of ovarian cancer resistance and covers sophisticated alternative pathways to overcome these resistance mechanisms in patients.

Identification of isobenzofuranone derivatives as promising antidiabetic agents: Synthesis, in vitro and in vivo inhibition of α-glucosidase and α-amylase, computational docking analysis and molecular dynamics simulations.

Diabetes mellitus, one of the major health challenges of the 21st century, is associated with numerous biomedical complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases and liver disorders. To control the chronic hyperglycemic condition, the development of potential inhibitors of drug targets such as α-glucosidase and α-amylase remains a promising strategy and focus of continuous efforts. Therefore, in the present work, a concise library of isobenzofuranone derivatives (3a-q) was designed and synthesized using Suzuki-Miyaura cross-coupling approach. The biological potential of these heterocyclic compounds against carbohydrate-hydrolyzing enzymes; α-glucosidase and α-amylase, was examined. In vitro inhibitory results demonstrated that the tested isobenzofuranones were considerably more effective and potent inhibitors than the standard drug, acarbose. Compound 3d having an IC50 value of 6.82 ± 0.02 µM was emerged as the lead candidate against α-glucosidase with ⁓127-folds strong inhibition than acarbose. Similarly, compound 3g demonstrated ⁓11-folds higher inhibition strength against α-amylase when compared with acarbose. Both compounds were tested in vivo and results demonstrate that the treatment of diabetic rats with α-amylase inhibitor show more pronounced histopathological normalization in kidney and liver than with α-glucosidase inhibitor. The Lineweaver-Burk plot revealed an uncompetitive mode of inhibition for 3d against α-glucosidase whereas compound 3g exhibited mixed inhibition against α-amylase. Furthermore, in silico molecular docking and dynamics simulations validated the in vitro data for these compounds whereas pharmacokinetics profile revealed the druglike properties of potent inhibitors.

Optimization of K2CO3 exposure conditions using response surface methodology for CO2 capture with 2-methylpiperazine and monoethanolamine as promoters.

In this study, the optimization of potassium carbonate (K2CO3) exposure conditions for CO2 capture with the use of 2-methypiperazine (2MPz) and monoethanolamine (MEA) as promoters was investigated. The tested operating conditions for the CO2 capture process included the pH, temperature, K2CO3 dose, gas flow rate, and pressure, and their effect on the CO2 absorption/desorption rate and CO2 absorption efficiency was assessed. Response surface methodology (RSM) was also employed to determine the equations for the optimal long-term operating conditions. The results showed that the CO2 absorption rate and efficiency increased under K2CO3 exposure with an increase in the pressure and loading rate. Moreover, for the temperature the absorption efficiency first increase and then decreases with increase in temperature, however, the with increase in temperature the faster absorption were observed with lower absorption loading rate. Furthermore, pH had a more complex effect due to its variable effects on the speciation of bicarbonate ions (HCO3-) and carbonate ions (CO32-). Under higher pH conditions, there was an increase in the concentration of HCO3-, which has a higher CO2 loading capacity than CO32-. Contouring maps were also used to visualize the effect of different exposure conditions on the CO2 absorption rate and efficiency and the role of 2MPz and MEA as promoters in the K2CO3 solution for CO2 absorption. The results showed that the mean CO2 absorption rate was 6.76 × 10-4 M/L/s with an R2 of 0.9693 for the K2CO3 solution containing 2MPz. The highest absorption rate (6.56-7.20 × 10-4 M/L/s) was observed at a temperature of 298-313 K, a pressure of >2 bar, a pH of 8-9, and a loading rate of 80-120 L/h for a concentration of 1-3 M K2CO3 and 0.05-1.5 M 2MPz. The CO2 absorption efficiency exhibited a variation of 56-70% under the same conditions.

Fabrication and evaluation of anticancer potential of diosgenin incorporated chitosan-silver nanoparticles; in vitro, in silico and in vivo studies.

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 µg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.

Probiotics and their Beneficial Health Effects.

Probiotics are living microorganisms that are present in cultured milk and fermented food. Fermented foods are a rich source for the isolation of probiotics. They are known as good bacteria. They have various beneficial effects on human health including antihypertensive effects, antihypercholesterolemic effects, prevention of bowel disease, and improving the immune system. Microorganisms including bacteria, yeast, and mold are used as probiotics but the major microorganisms that are used as probiotics are bacteria from the genus Lactobacillus, Lactococcus, Streptococcus, and Bifidobacterium. Probiotics are beneficial in the prevention of harmful effects. Recently, the use of probiotics for the treatment of various oral and skin diseases has also gained significant attention. Clinical studies indicate that the usage of probiotics can alter gut microbiota composition and provoke immune modulation in a host. Due to their various health benefits, probiotics are attaining more interest as a substitute for antibiotics or anti-inflammatory drugs leading to the growth of the probiotic market.

One-dimensional modeling of heterogeneous catalytic chemical looping steam methane reforming in an adiabatic packed bed reactor.

Hydrogen production via chemical looping steam methane reforming (CL-SMR) is among the most promising current technologies. This work presents the development in gPROMS Model Builder 4.1.0® of a 1D model of an adiabatic packed bed reactor used for chemical looping reforming (CLR). The catalyst used for this process was 18 wt. % NiO with the support of Al2O3. A brief thermodynamic analysis using Chemical Equilibrium Application (CEA) was carried out to identify the optimum operating conditions. The model was simulated for 10 complete CL-SMR cycles. The effects of variations in temperature, pressure, gas mass velocity, nickel oxide concentration, reactor length, and particle diameter were studied to investigate the performance of the CL-SMR process under these variations. A parametric analysis was carried out for different ranges of conditions: temperatures from 600 to 1,000 K, pressure from 1 to 5 bar, gas mass velocity between 0.5 and 0.9 kg·m-2 s-1, nickel oxide concentration values between 0.1 and 1 mol·m-3, particle diameters between 0.7 and 1 mm, and fuel reactor (FR) lengths between 0.5 and 1.5 m. At the optimum temperature (950 K), pressure (1 bar), and steam-to-carbon molar ratio (3/1), with an increase in particle diameter from 0.7 to 1 mm, an 18% decrease in methane conversion and a 9.5% increase in hydrogen yield were observed. Similarly, with an increase in FR length from 0.5 m to 1.5 m, a delay in the temperature drop was observed.

Identification of potential inhibitors targeting yellow fever virus helicase through ligand and structure-based computational studies.

Yellow fever is a flavivirus having plus-sensed RNA which encodes a single polyprotein. Host proteases cut this polyprotein into seven nonstructural proteins including a vital NS3 protein. The present study aims to identify the most effective inhibitor against the helicase (NS3) using different advanced ligand and structure-based computational studies. A set of 300 ligands was selected against helicase by chemical structural similarity model, which are similar to S-adenosyl-l-cysteine using infiniSee. This tool screens billions of compounds through a similarity search from in-built chemical spaces (CHEMriya, Galaxi, KnowledgeSpace and REALSpace). The pharmacophore was designed from ligands in the library that showed same features. According to the sequence of ligands, six compounds (29, 87, 99, 116, 148, and 208) were taken for pharmacophore designing against helicase protein. Subsequently, compounds from the library which showed the best pharmacophore shared-features were docked using FlexX functionality of SeeSAR and their optibrium properties were analyzed. Afterward, their ADME was improved by replacing the unfavorable fragments, which resulted in the generation of new compounds. The selected best compounds (301, 302, 303 and 304) were docked using SeeSAR and their pharmacokinetics and toxicological properties were evaluated using SwissADME. The optimal inhibitor for yellow fever helicase was 2-amino-N-(4-(dimethylamino)thiazol-2-yl)-4-methyloxazole-5-carboxamide (302), which exhibits promising potential for drug development.Communicated by Ramaswamy H. Sarma.

Preparation and investigation of a novel combination of Solanum nigrum-loaded, arabinoxylan-cross-linked ß-cyclodextrin nanosponges for the treatment of cancer: in vitro, in vivo, and in silico evaluation.

Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability. Methods: In this study, Solanum nigrum, an effective medicinal plant, loaded arabinoxylan cross-linked ß-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters. Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, -29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 µg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that ß-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = -10.1 Kcal/mol). Conclusion: Therefore, findings of current study elucidated the therapeutic potential of ß-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs.

Urease inhibitory potential of pyridine-containing triazolothiadiazole and triazolothiadiazine scaffolds for the treatment of ulceration and kidney stone: in vitro screening, kinetics mechanism, and in silico computational analysis.

The hyperactivity of urease enzyme leads to various complications including gastritis and peptic ulcer. A diverse variety of natural and synthetic inhibitors have shown a tremendous potential to inhibit the urease enzyme, thus decreasing the hyperactivity and reducing the risk for the development of urinary calculi and other similar problems. Therefore, we herein report a family of fused heterocycles such as triazolothiadiazoles (4a-h, 5a-f) and triazolothiadiazines (6a-h) as potential antiurease agents with IC50 values in the range 10.41-41.20 µM. Several compounds were identified as potential lead candidates. Among them, compounds 4e and 4f from triazolothiadiazole series showed the highest inhibitory potential with IC50 values of 11.62 ± 0.34 and 10.35 ± 0.14 µM), respectively, whereas 6e from triazolothiadiazine series emerged as the most potent inhibitor with an IC50 value of 10.41 ± 0.13 µM. These compounds exhibited two-fold strong inhibitory efficacy against urease as compared to standard inhibitor, thiourea (IC50 = 22.48 ± 0.67 µM). The mechanistic insights from kinetics experiments for compounds 4e, 4f, and 6e revealed the competitive mode of inhibition with Ki values of 8.65 ± 0.004, 7.04 ± 0.012, and 8.31 ± 0.007 µM, respectively. The in vitro results were further explored through in silico computational docking analysis which reflects that binding of ligands with Ni ions and His492 play a crucial role in urease inhibition. In silico predicted physicochemical properties and ADME profile reflect drug-like nature of these molecules.Communicated by Ramaswamy H. Sarma.

Direct Growth of Nitrogen-Doped Carbon Quantum Dots on Co9S8 Passivated on Cotton Fabric as an Efficient Photoelectrode for Water Treatment.

Heterogeneous growth of photocatalysts on different porous substrates is a solution to avoid secondary pollution caused by composite photocatalysts themselves. However, the heterogeneous growth of composite photocatalysts with nitrogen-doped carbon quantum dots (NCQDs) inclusions-introduced during synthesis-impedes the direct growth on the substrate. To overcome this problem, NCQDs were grown on a Co9S8 (NCQDs-G@Co9S8) layer, decorated on cotton fabric. This optimal coupling mode of NCQDs and Co9S8 showed 54% degradation, compared to 33% dye degradation via NCQDs-doped Co9S8 (NCQDs-D@Co9S8). The change in the crystal structure and its lower loading on fabric results in significantly lower performance of NCQDs-D@Co9S8. Even with the combination of both surface growth and doping (NCQDs-DG@Co9S8), the performance was still limited to 42%. In addition, the optimum growth concentration of NCQDs on Co9S8 was observed for 7.5 w/w %, resulting in 92% photocatalytic activity (PCA) in 80 min. Comparing different surface states formed in NCQDs using different solvents, water-based surface states (oxygen-rich surface) are most suitable for the dye degradation. NCQDs-G@Co9S8 also offers 67% Cr-VI reduction to Cr-III, showing its suitability for both inorganic and organic compounds. Better electrode performance was related to suitable charge separation of the composite, where -OH groups mainly contribute in the photocatalytic dye degradation..

Industrial wastewater irrigation increased higher heavy metals uptake and expansins, metacaspases, and cystatin genes expression in Parthenium and maize.

Industrial wastewater irrigation of agricultural crops can cause a lot of environmental and health problems in developing countries due to heavy metals deposition in agricultural soils as well as edible plant consumption by human beings. Therefore, this study was conducted to find out the heavy metals concentration in industrial wastewater and soil irrigated with that wastewater. In addition, the aim was to determine the impact of industrial wastewater irrigation on Parthenium hysterophorus and Zea mays genes involved in growth improvement and inhibition. For this purpose, plant samples from agriculture fields irrigated with wastewater from Hattar Industrial Estate (HIE) of Haripur, Pakistan, and control plants from non-contaminated soil irrigated with tape water were collected after 15 and 45 days of germination. Heavy metals concentration in the collected plant samples, wastewater, and soil was determined. The results revealed that the soil of the sample collection site was predominantly contaminated with Cr, Pb, Ni, Cu, Co, Zn, and Cd up to the concentrations of 38.98, 21.14, 46.01, 155.73, 12.50, 68.50, and 7.01 mg/kg, respectively. The concentrations of these heavy metals were found to surpass the permissible limit in normal agricultural soil. Expansins, cystatins (plant growth enhancers), and metacaspases (plant growth inhibitor) gene expression were studied through reverse transcription polymerase chain reaction. The results showed that the expression of these genes was higher in samples collected from wastewater-irrigated soils as compared to control. The expression of these genes was observed in 45 days old samples, 15 days old samples, and control. Taken together, this study suggests the use of Parthenium and maize for phytoremediation and that they should not be used for eating purposes if irrigated with industrial wastewater.

Evaluation of Organic and Inorganic Foulant Interaction Using Modified Fouling Models in Constant Flux Dead-End Operation with Microfiltration Membranes.

The goal of this study was to elucidate the interaction of complex feed solutions under modified membrane fouling models for constant flux operation. The polyvinylidene fluoride membrane (PVDF) was tested for three types of solutions containing inorganic foulants (Al, Mn, and Fe), organic foulants, and suspended solids at 0.5 mM Ca2+ ionic strength. The membrane's performance was evaluated by measuring the increase in transmembrane pressure (TMP) during two different filtration scenarios: continuous filtration lasting 1 h and cyclic filtration lasting 12 min, with 3 min backwashing cycles included. Statistical analysis (linear regression results (R2), p-value) was used to verify the fouling model propagation along with the determination of the contributing constant of each fouling model. An increasing TMP percentage of 164-302%, 155-300%, and 208-378% for S1 (HA + Ca2+), S2 (inorganics + kaolin + Ca2+), and S3 (HA + inorganics + kaolin + Ca2+) was recorded for 1 h filtration, respectively. Furthermore, a five percent increase in irreversible resistance was noted for the S3 solution due to the strong adsorption potential of foulants for the PVDF membrane caused by the electrostatic and hydration forces of foulants. In addition to that, the participation equation elucidated the contribution of the fouling model and confirmed that complete blocking and cake layer contribution were dominant for the S1 and S3 solutions, while standard blocking was dominant for the S2 solution with a high significance ratio. Moreover, R2 and cyclic filtration analysis also confirmed the propagation of these fouling models. The statistical confirmation and regression results analysis of the modified model gave comparative results and satisfied the filtration mechanism and can be used for the constant flux dead filtration analysis of water treatment.

Purinergic Signaling and its Role in the Stem Cell Differentiation.

Purinergic signaling is a mechanism in which extracellular purines and pyrimidines interact with specialized cell surface receptors known as purinergic receptors. These receptors are divided into two families of P1 and P2 receptors, each responding to different nucleosides and nucleotides. P1 receptors are activated by adenosine, while P2 receptors are activated by pyrimidine and purines. P2X receptors are ligand-gated ion channels, including seven subunits (P2X1-7). However, P2Y receptors are the G-protein coupled receptors comprising eight subtypes (P2Y1/2/4/6/11/12/13/14). The disorder in purinergic signaling leads to various health-related issues and diseases. In various aspects, it influences the activity of non-neuronal cells and neurons. The molecular mechanism of purinergic signaling provides insight into treating various human diseases. On the contrary, stem cells have been investigated for therapeutic applications. Purinergic signaling has shown promising effect in stem cell engraftment. The immune system promotes the autocrine and paracrine mechanisms and releases the significant factors essential for successful stem cell therapy. Each subtype of purinergic receptor exerts a beneficial effect on the damaged tissue. The most common effect caused by purinergic signaling is the proliferation and differentiation that treat different health-related conditions.

Discovery of druggable potent inhibitors of serine proteases and farnesoid X receptor by ligand-based virtual screening to obstruct SARS-CoV-2.

The coronavirus, a subfamily of the coronavirinae family, is an RNA virus with over 40 variations that can infect humans, non-human mammals and birds. There are seven types of human coronaviruses, including SARS-CoV-2, is responsible for the recent COVID-19 pandemic. The current study is focused on the identification of drug molecules for the treatment of COVID-19 by targeting human proteases like transmembrane serine protease 2 (TMPRSS2), furin, cathepsin B, and a nuclear receptor named farnesoid X receptor (FXR). TMPRSS2 and furin help in cleaving the spike protein of the SARS-CoV-2 virus, while cathepsin B plays a critical role in the entry and pathogenesis. FXR, on the other hand, regulates the expression of ACE2, and its inhibition can reduce SARS-CoV-2 infection. By inhibiting these four protein targets with non-toxic inhibitors, the entry of the infectious agent into host cells and its pathogenesis can be obstructed. We have used the BioSolveIT suite for pharmacophore-based computational drug designing. A total of 1611 ligands from the ligand library were docked with the target proteins to obtain potent inhibitors on the basis of pharmacophore. Following the ADMET analysis and protein ligand interactions, potent and druggable inhibitors of the target proteins were obtained. Additionally, toxic substructures and the less toxic route of administration of the most potent inhibitors in rodents were also determined computationally. Compounds namely N-(diaminomethylene)-2-((3-((1R,3R)-3-(2-(methoxy(methyl)amino)-2-oxoethyl)cyclopentyl)propyl)amino)-2-oxoethan-1-aminium (26), (1R,3R)-3-(((2-ammonioethyl)ammonio)methyl)-1-((4-propyl-1H-imidazol-2-yl)methyl)piperidin-1-ium (29) and (1R,3R)-3-(((2-ammonioethyl)ammonio)methyl)-1-((1-propyl-1H-pyrazol-4-yl)methyl)piperidin-1-ium (30) were found as the potent inhibitors of TMPRSS2, whereas, 1-(1-(1-(1H-tetrazol-1-yl)cyclopropane-1­carbonyl)piperidin-4-yl)azepan-2-one (6), (2R)-4-methyl-1-oxo-1-((7R,11S)-4-oxo-6,7,8,9,10,11-hexahydro-4H-7,11-methanopyrido[1,2-a]azocin-9-yl)pentan-2-aminium (12), 4-((1-(3-(3,5-dimethylisoxazol-4-yl)propanoyl)piperidin-4-yl)methyl)morpholin-4-ium (13), 1-(4,6-dimethylpyrimidin-2-yl)-N-(3-oxocyclohex-1-en-1-yl)piperidine-4-carboxamide (14), 1-(4-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(3,5-dimethylisoxazol-4-yl)propan-1-one (25) and N,N-dimethyl-4-oxo-4-((1S,5R)-8-oxo-5,6-dihydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-3(2H,4H,8H)-yl)butanamide (31) inhibited the FXR preferentially. In case of cathepsin B, N-((5-benzoylthiophen-2-yl)methyl)-2-hydrazineyl-2-oxoacetamide (2) and N-([2,2'-bifuran]-5-ylmethyl)-2-hydrazineyl-2-oxoacetamide (7) were identified as the most druggable inhibitors whereas 1-amino-2,7-diethyl-3,8-dioxo-6-(p-tolyl)-2,3,7,8-tetrahydro-2,7-naphthyridine-4­carbonitrile (5) and (R)-6-amino-2-(2,3-dihydroxypropyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (20) were active against furin.

Managing Weed-Crop Interactions Enhances Chickpea (Cicer arietinum L.) Chemical Components.

Chickpea (Cicer arietinum L.) is a major pulse crop worldwide, renowned for its nutritional richness and adaptability. Weeds are the main biotic factor deteriorating chickpea yield and nutritional quality, especially Asphodelus tenuifolius Cav. The present study concerns a two-year (2018-19 and 2019-20) field trial aiming at evaluating the effect of weed management on chickpea grain quality. Several weed management practices have been here implemented under a factorial randomized complete block design, including the application of four herbicides [bromoxynil (C7H3Br2NO) + MCPA (Methyl-chlorophenoxyacetic acid) (C9H9ClO3), fluroxypyr + MCPA, fenoxaprop-p-ethyl (C18H16ClNO5), pendimethalin (C13H19N3O4)], the extracts from two allelopathic weeds (Sorghum halepense and Cyperus rotundus), two mulches (wheat straw and eucalyptus leaves), a combination of A. tenuifolius extract and pendimethalin, and an untreated check (control). Chickpea grain quality was measured in terms of nitrogen, crude protein, crude fat, ash, and oil content. The herbicides pendimethalin (Stomp 330 EC (emulsifiable concentrate) in pre-emergence at a rate of 2.5 L ha-1) and fenoxaprop-p-ethyl (Puma Super 7.5 EW (emulsion in water) in post-emergence at a rate of 1.0 L ha-1), thanks to A. tenuifolius control, showed outstanding performance, providing the highest dietary quality of chickpea grain. The herbicides Stomp 330 EC, Buctril Super 40 EC, Starane-M 50 EC, and Puma Super 7.5 EW provided the highest levels of nitrogen. Outstanding increases in crude protein content were observed with all management strategies, particularly with Stomp 330 EC and Puma Super 7.5 EW (+18% on average). Ash content was highly elevated by Stomp 330 EC and Puma Super 7.5 EW, along with wheat straw mulching, reaching levels of 2.96% and 2.94%. Crude fat content experienced consistent elevations across all treatments, with the highest improvements achieved by Stomp 330 EC, Puma Super 7.5 EW, and wheat straw mulching applications. While 2018-19 displayed no significant oil content variations, 2019-20 revealed the highest oil content (5.97% and 5.96%) with herbicides Stomp 330 EC and Puma Super 7.5 EW, respectively, followed by eucalyptus leaves mulching (5.82%). The results here obtained are of key importance in the agricultural and food sector for the sustainable enhancement of chickpea grain's nutritional quality without impacting the environment.

Role of inorganic foulants in the aging and deterioration of low-pressure membranes during the chemical cleaning process in surface water treatment: A review.

Low-pressure membrane (LPM) filtration, including microfiltration (MF) and ultrafiltration (UF), is a promising technology for the treatment of surface water for drinking and other purposes. Various configurations and operational sequences have been developed to ensure the sustainable provision of clean water by overcoming fouling problems. In the literature, various periodic physical and/or chemical approaches to the cleaning of LPMs have been reported, but little data is available on the aging of MF/UF membranes that results from the interaction between the foulants and the cleaning agent. Periodic physical cleaning of the membrane is expected to return the membrane to its original performance capacity, but it only recovers to a certain level because the remaining foulants cause irreversible fouling. Chemical cleaning can then be employed to recover the membrane from this irreversible fouling but, in the process, it can cause irrecoverable damage to the membrane. In this review, the foulants responsible for irrecoverable damage to MF/UF membranes are summarized, and their interaction with cleaning agents and other foulants is described. The impact of these foulants on various membrane parameters, including filtration efficiency, flux decline, permeability, membrane characterization, and membrane integrity are also summarized and discussed in detail. In addition, mitigation options and future prospects are also discussed with regard to increasing the operational life span of a membrane in a cost-effective manner. Ultimately, this review suggests an advanced control system based on membrane-foulant interactions under the impact of various operational parameters to mitigate the integrity loss of membranes.