Novel saturated 1,2,4-trioxanes and their antimalarial activity against multidrug resistant Plasmodium yoelii nigeriensis in Swiss mice model via oral route.

Novel saturated 6-(4'-aryloxy phenyl) vinyl 1,2,4-trioxanes 12a(1-3)-12d(1-3) and 13a(1-3)-13d(1-3) have been designed and synthesized, in one single step from diimide reduction of 11a(1-3)-11d(1-3). All the newly synthesized trioxanes were evaluated for their antimalarial activity against multi-drug resistant Plasmodium yoelii nigeriensis via oral route. Cyclopentane-based trioxanes 12b1, 12c1 and 12d1, provided 100 % protection to the infected mice at 24 mg/kg × 4 days. The most active compound of the series, trioxane 12b1, provided 100 % protection even at 12 mg/kg × 4 days and 60 % protection at 6 mg/kg × 4 days. The currently used drug, ß-arteether provides only 20 % protection at 24 mg/kg × 4 days.

The possible role of nuclear factor erythroid-2-related factor 2 activators in the management of Covid-19.

COVID-19 is caused by a novel SARS-CoV-2 leading to pulmonary and extra-pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID-19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS-CoV-2-induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclear factor erythroid 2-related factor 2 (Nrf2), which induces a series of cellular interactions to mitigate SARS-CoV-2-mediated viral toxicity and OS-induced cellular injury. Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm in COVID-19. Therefore, Nrf2 activators may play an essential role in reducing SARS-CoV-2 infection-induced inflammation by suppressing NLRP3 inflammasome in COVID-19. Furthermore, Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Thus this mini-review tries to clarify the possible role of the Nrf2 activators in the management of COVID-19. Nrf2 activators could be an effective therapeutic strategy in the management of Covid-19. Preclinical and clinical studies are recommended in this regard.

Effects of vermicompost on soil microbiological properties in lettuce rhizosphere: An environmentally friendly approach for sustainable green future.

The aim of this study is to investigate the effects of vermicompost on the biological and microbial properties of lettuce rhizosphere in an agricultural field in Samsun, Turkey. The experiment was conducted in a completely randomised design (CRD) and included four vermicompost dosages (0%, 1%, 2%, and 4%) and two application methods (with and without plants). Batavia lettuce was selected as the test plant due to its sensitivity to environmental conditions and nutrient deficiencies. The study evaluated the changes in organic matter (OM), pH, electrical conductivity (EC), carbon dioxide (CO2), dehydrogenase activity (DHA), microbial biomass carbon (MBC), and catalase activity (CA) in the rhizosphere of lettuce plants treated with different vermicompost levels (0%, 1%, 2%, and 4%). The findings showed that vermicompost application significantly increased chlorophyll content in lettuce plants, with the highest content observed in plants treated with V1 compared to the control. Different vermicompost concentrations also influenced chlorophyll b and total chlorophyll levels, with positive effects observed at lower concentrations than the control. Plant height and fresh weight were highest in plants treated with V2, indicating the positive impact of vermicompost on plant growth. Additionally, vermicompost application increased plant dry weight and improved soil properties such as pH, organic matter content, and microbial activity. The findings showed that vermicompost increased the rhizosphere's microbial biomass and metabolic activity, which can be beneficial for plant growth and disease suppression. The study highlights the importance of understanding the effects of organic amendments on soil properties and the microbial community in the rhizosphere, which can contribute to sustainable agricultural practices. Overall, the results suggest that vermicompost can be used as an effective organic amendment for enhancing plant growth and improving soil properties in agricultural fields. Moreover, based on the data, it can be suggested that a dose between 1% and 2% vermicompost is beneficial for the overall growth of plants.

Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2.

Owing to the urgent need for therapeutic interventions against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potentials of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C9 scored highest against all targets. C11 scored highest against Spro and C12 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 - ASP 289 - GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies.

Electrochemical sensing base for hazardous herbicide aclonifen using gadolinium niobate (GdNbO4) nanoparticles-actual river water and soil sample analysis.

The present work scrutinized the voltammetric analysis of hazardous herbicide aclonifen (ACF) in actual soil and river water samples utilizing the electrochemical method. The electrochemical sensing device was fabricated for the determination of ACF using gadolinium niobate (GdNbO4) nanoparticles modified glassy carbon electrode (GCE). The novel GdNbO4 sensing material was prepared via a simple co-precipitation method. Several characterization techniques (TEM, EDS, XRD, XPS, and BET) were utilized to analyze the structural features of the GdNbO4. The enhanced electrochemical behavior of GdNbO4 modified GCE towards ACF was observed compared to bare GCE. The cyclic voltammetry response revealed that the prepared sensor shows the lower negative potential with a dramatic increase in the peak current of ACF compared to bare GCE. In the differential pulse voltammetry, the limit of detection (1.15 nM) and sensitivity (23 µA µM-1 cm-2) of the ACF on the GdNbO4 modified GCE was comparatively superior to the formerly proposed ACF based sensor. This sensor reveals good selectivity, repeatability, reproducibility, and long-term stability. The reliability of the sensor exhibits satisfactory recovery results for ACF detection in river water and soil samples.

Regulatory Role of Nano-Curcumin against Tartrazine-Induced Oxidative Stress, Apoptosis-Related Genes Expression, and Genotoxicity in Rats.

The present study evaluates the regulatory effect of Nano-Curcumin (Nano-CUR) against tartrazine (TZ)-induced injuries on apoptosis-related gene expression (i.e., p53, CASP-3 and CASP-9), antioxidant status, and DNA damages in bone marrow in treated rats. Male rats were arbitrarily separated into five groups, and each group was comprised of 10 rats each. The 1st group served as control (G1). The 2nd group ingested 7.5 mg TZ/kg. b.w. (body weight). The 3rd group ingested Nano-CUR 1 g/kg b.w. The 4th and 5th groups were respectively administered with (1 g Nano-CUR + 7.5 mg TZ/kg. b.w.) and (2 g Nano-CUR + 7.5 mg TZ/kg. b.w.). At the end of the experiment, blood samples, livers, and kidneys were collected. Livers and kidneys were homogenized and used for the analysis of reduced glutathione, malonaldhyde, total antioxidant capacity, lipid peroxide antioxidant enzyme activities, apoptosis-related gene expression, and genotoxicity by comit test. The ingestion of TZ for 50 days resulted in significant decreases in body, and kidney weights in rats and a relative increase in the liver weight compared to control. In contrast, the ingestion of Nano-CUR with TZ remarkably upgraded the body weight and relative liver weight compared to the normal range in the control. Aditionally, TZ ingestion in rats increased the oxidative stress biomarkers lipid peroxide (LPO) and malonaldehyde (MDA) significantly, whereas it decreased the reduced glutathione (GSH) levels and total antioxidant capacity (TAC). Similarly, the levels of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) significantly deteriorated in response to TZ ingestion. Moreover, the results revealed a remarkable up-regulation in the level of expression for the three examined genes, including p53, CASP-3, and CASP-9 in TZ-ingested rats compared to the control. On the other hand, the comet assay result indicates that the ingestion of TZ induced DNA damage in bone marrow. Notably, the administration of Nano-CUR protected the kidney and liver of TZ-ingested rats as evidenced by a significant elevation in all antioxidant activities of tested enzymes (i.e, SOD, GPx, and CAT), vital recovery in GSH and TAC levels, and a statistical decrease in LPO and MDA compared to TZ-ingested rats. Interestingly, the ingestion of rats with TZ modulates the observed up-regulation in the level of expression for the chosen genes, indicating the interfering role in the signaling transduction process of TZ-mediated poisoning. The results indicate that the administration of Nano-CUR may protect against TZ-induced DNA damage in bone marrow. According to the results, Nano-CUR exerted a potential protective effect against oxidative stress, DNA damage, and the up-regulation of apoptosis-related genes induced by TZ ingested to rats.

Probiotics in poultry feed: A comprehensive review.

The use of antibiotics to maintain animal well-being, promote growth and improve efficiency has been practised for more than 50 years. However, as early as the 1950s, researchers identified concern on the development of resistant bacteria for the antibiotics streptomycin and tetracycline used in turkeys and broilers respectively. These findings laid the groundwork for agricultural officials to impose stricter regulatory parameters on the use of antibiotics in poultry feeds. Probiotics are live micro-organisms included in the diet of animals as feed additives or supplements. Commonly known as a direct-fed microbial, probiotics provide beneficial properties to the host, primarily through action in the gastrointestinal tract (GIT) of the animal. Supplementation of probiotics in the diet can improve animal health and performance, through contributions to gut health and nutrient use. For instance, supplementation of probiotics has been demonstrated to benefit farm animals in immune modulation, structural modulation and increased cytokine production, which positively affect the intestinal mucosal lining against pathogens. Bacillus subtilis has been a popular bacterium used within the industry and was shown to improve intestinal villus height. Increasing the villus height and structure of the crypts in the GIT allows for the improvement of nutrient digestion and absorption. Tight junctions maintain important defences against pathogenic bacteria and cellular homeostasis. Heat stress can be a major environmental challenge in the poultry industry. Heat stress causes the bird to fluctuate its internal core temperature beyond their comfort zone. To overcome such challenges, poultry will attempt to balance its heat production and dissipation through behavioural and physiological adaptation mechanisms.

Effects of the dietary inclusion of a probiotic or prebiotic on florfenicol pharmacokinetic profile in broiler chicken.

We evaluated the effect of prebiotic or probiotic as feed additives on florfenicol kinetic in broilers feed. Unsexed two hundred, thirty-five-day-old broiler chickens, were put in four equal groups (n = 50). The first group was administrated florfenicol intravenous at 30 mg/kg body weight (BW) only once dosage without pre- or probiotic administration to determine the bioavailability. While, the second group was administrated florfenicol (intracrop routes; a dosage of 30 mg/kg BW for five progressive days) without pre- or probiotic co-administration. The third and the fourth groups were administrated the same dose of florfenicol (intracrop route) for five successive days, followed by 10 days of prebiotic or probiotic treatment respectively. The plasma florfenicol % was identified by high-pressure liquid chromatography (HPLC) after the first florfenicol administration (intravenous or intracrop routes) in all groups. Then, the residual levels of florfenicol were determined in liver, kidney and muscle tissues from the second, third and fourth groups which were exposed to florfenicol orally. Our results demonstrated that broilers pre-treated with prebiotic or probiotic significantly increased Cmax , AUC0- t , AUC0-inf as well as AUMC values, while significant drop was recorded in V/F and CL/F. Prebiotic or probiotic influenced the cumulative effect of florfenicol in liver and kidney tissues of treated birds.

The fluorescence quenching of Ru(bipy)32+ : an application for the determination of bilirubin in biological samples.

A simple, sensitive and efficient fluorescence method has been established for the quantitative analysis of bilirubin. The fluorometric determination method was based on the kinetic quenching of ruthenium(II) fluorescence. The quenching effect may be due to the complexation reaction of bilirubin with ruthenium(II). Therefore, the effects of ruthenium concentrations and different surfactants have been studied. Under the optimized experimental parameters, the fluorescence intensity decreased proportionally with the bilirubin concentration and linearity was established in the range of 3.3 × 10-7 to 3.0 × 10-4  M bilirubin. The detection limit calculated from the calibration graph was found to be 5.2 × 10-8  M. The relative standard deviation (RSD) of 10 consecutive measurements of 8.0 × 10-6  M bilirubin was 3.0%, while the recoveries of bilirubin in both human serum and urine samples were obtained in the range 94.0-99.5%. The interference study shows that the developed fluorescence based technique is fast, easy to carry out and shows negligible interference. The developed technique was successfully applied for the analysis of bilirubin in human urine and serum samples. All the experimental results and quality parameters confirmed the sensitivity and reproducibility of the proposed technique for bilirubin determination in human urine and serum samples.

Effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca(2+) transport in Goto-Kakizaki type 2 diabetic rat heart.

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca(2+) transport in the Goto-Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), intercellular proteins (Gja4), cell membrane transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), intercellular proteins (Gja1 and Gja4), intracellular Ca(2+) transport (Atp2a1 and Ryr2), cell membrane transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control-sucrose group compared with control rats and in the GK-sucrose group compared with GK rats. The amplitude of the Ca(2+) transient was increased in myocytes from control-sucrose compared with control rats and decreased in GK-sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intracellular Ca(2+) transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet.

Seasonal concentrations of lead in outdoor and indoor dust and blood of children in Riyadh, Saudi Arabia.

Because detrimental effects of exposure to lead (Pb) on human health have been observed, we previously investigated concentrations of Pb in water supplies and blood of adult residents of Riyadh, Saudi Arabia. The objectives of the present study were to: (1) examine seasonal rates of deposition of Pb in dust in several areas of Riyadh city, (2) measure concentrations of Pb in both outdoor and indoor dust, (3) compare concentrations of Pb in dust in Riyadh with those reported for other cities, and (4) quantify Pb in blood of children living in Riyadh. Mean, monthly deposition of PB in outdoor dust was 4.7 × 10(1) ± 3.6 tons km(-2), with a mean Pb concentration of 2.4 × 10(2) ± 4.4 × 10(1) µg/g. Mean, monthly deposition of Pb in indoor dust was 2.7 ± 0.70 tons km(-2), with a mean concentration of 2.9 × 10(1) ± 1.5 × 10(1) µg Pb/g. There was a significant (P < 0.01) correlation between concentrations of Pb in outdoor and indoor dust. There was no correlation between concentrations of Pb in indoor dust and that in blood of children of Riyadh, whereas there was a weakly significant (P < 0.05) correlation between concentrations of Pb in outdoor dust and that in blood of children. The mean (±SD) concentration of Pb in blood of children in Riyadh was 5.2 ± 1.7, with a range of 1.7-1.6 × 10(1) µg/dl. Concentrations of Pb in blood of 17.8 % of children in Riyadh were greater than 10 µg/dl, which is the CDC's level of concern.

Identification of novel hit molecules targeting M. tuberculosis polyketide synthase 13 by combining generative AI and physics-based methods.

In this work we investigated the Pks13-TE domain, which plays a critical role in the viability of the mycobacteria. In this report, we have used a series of AI and Physics-based tools to identify Pks13-TE inhibitors. The Reinvent 4, pKCSM, KDeep, and SwissADME are AI-ML-based tools. AutoDock Vina, PLANTS, MDS, and MM-GBSA are physics-based methods. A combination of these methods yields powerful support in the drug discovery cycle. Known inhibitors of Pks13-TE were collected, curated, and used as input for the AI-based tools, and Mol2Mol molecular optimisation methods generated novel inhibitors. These ligands were filtered based on physics-based methods like molecular docking and molecular dynamics using multiple tools for consensus generation. Rigorous analysis was performed on the selected compounds to reduce the chemical space while retaining the most promising compounds. The molecule interactions, stability of the protein-ligand complexes and the comparable binding energies with the native ligand were essential factors for narrowing the ligands set. The filtered ligands from docking, MDS, and binding energy colocations were further tested for their ADMET properties since they are among the essential criteria for this series of molecules. It was found that ligands Mt1 to Mt6 have excellent predicted pharmacokinetic, pharmacodynamic and toxicity profiles and good synthesisability.

Identification of Mycobacterium tuberculosis transcriptional repressor EthR inhibitors: Shape-based search and machine learning studies.

Tuberculosis has been a challenge to the world since prehistoric times, and with the advent of drug-resistant strains, it has become more challenging to treat this infection. Ethionamide (ETH), a second-line drug, acts as a prodrug and targets mycolic acid synthesis by targeting the enoyl-acyl carrier protein reductase (InhA) enzyme. Mycobacterium tuberculosis (Mtb) EthR is an ethA gene repressor required to activate prodrug ETH. Recent studies suggest targeting the EthR could lead to newer drug molecules that would help better activate the ETH or complement this process. In this report, we have attempted and successfully identified three new molecules from the drug repurposing library that can target EthR protein and function as ETH boosters. These molecules were obtained after rigorous filtering of the database for their physicochemical, toxicological properties and safety. The molecular docking, molecular dynamics simulations and binding energy studies yielded three compounds, Ethyl (2-amino-4-((4-fluorobenzyl)amino)phenyl)carbamate) (L1), 2-((2,2-Difluorobenzo [d] [1,3]dioxol-5-yl)amino)-2-oxoethyl (E)-3-(5-bromofuran-2-yl)acrylate (L2), and N-(2,3-Dihydrobenzo [b] [1,4]dioxin-6-yl)-4-(2-((4-fluorophenyl)amino)-2-oxoethoxy)-3-methoxy benzamide (L3) are potential EthR inhibitors. We applied machine learning methods to evaluate these molecules for toxicity and synthesisability, suggesting safety and ease of synthesis for these molecules. These molecules are known for other pharmacological activities and can be repurposed faster as adjuvant therapy for tuberculosis.

Deciphering the functional landscape and therapeutic implications of noncoding RNAs in the TGF-ß signaling pathway in colorectal cancer: A comprehensive review.

Colorectal cancer (CRC) remains a major global health concern, necessitating an in-depth exploration of the intricate molecular mechanisms underlying its progression and potential therapeutic interventions. Transforming Growth Factor-ß (TGF-ß) signaling, a pivotal pathway implicated in CRC plays a dual role as a tumor suppressor in the early stages and a promoter of tumor progression in later stages. Recent research has shed light on the critical involvement of noncoding RNAs (ncRNAs) in modulating the TGF-ß signaling pathway, introducing a new layer of complexity to our understanding of CRC pathogenesis. This comprehensive review synthesizes the current state of knowledge regarding the function and therapeutic potential of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the context of TGF-ß signaling in CRC. The intricate interplay between these ncRNAs and key components of the TGF-ß pathway is dissected, revealing regulatory networks that contribute to the dynamic balance between tumor suppression and promotion. Emphasis is placed on how dysregulation of specific ncRNAs can disrupt this delicate equilibrium, fostering CRC initiation, progression, and metastasis. Moreover, the review provides a critical appraisal of the emerging therapeutic strategies targeting ncRNAs associated with TGF-ß signaling in CRC. The potential of these ncRNAs as diagnostic and prognostic biomarkers is discussed, highlighting their clinical relevance. Additionally, the challenges and prospects of developing RNA-based therapeutics, such as RNA interference and CRISPR/Cas-based approaches, are explored in the context of modulating TGF-ß signaling for CRC treatment. In conclusion, this review offers a comprehensive overview of the intricate interplay between ncRNAs and the TGF-ß signaling pathway in CRC. By unraveling the functional significance of these regulatory elements, we gain valuable insights into the molecular landscape of CRC, paving the way for the development of novel and targeted therapeutic interventions aimed at modulating the TGF-ß signaling cascade through the manipulation of ncRNAs.

Trans-Chalcone (1-3-diphenyl-2-propen-1-one) as a Therapeutic Candidate in Joint Inflammation via Reduction of TNF-α, IL-1ß, IL-6, and IL-17 in Rodents: An In Vivo Study by RT-PCR and ELISA analysis.

Autoimmune disorders include vast and distinct illnesses and are characterized by an immune system-mediated attack on the body's own tissues. Because of their ability to impact any portion of the body, their clinical symptoms are incredibly varied. The variations in symptoms are normally linked with the release and activation of vasoactive, chemotactic substances and cytokines. Cytokines perform a multitude of vital biological tasks, such as immune response control, inflammation, proliferation, and tissue repair. The reversal of inflammatory cytokines and leukocyte infiltration into the inflamed tissue by natural compounds provides an effective remedy for autoimmune diseases. Here, the oral administration of trans-chalcone (TC) for 28 days was tested with gradually increasing doses (30, 60, and 120 mg/kg) in complete Freund's adjuvant (CFA)-provoked joint tissue stiffness in rats. Paw edema, arthritic index, joint stiffness, thermal and flexion pain, C-reactive protein, and rheumatoid factor (RF) levels were determined to check the tested drug effectiveness in a chronic inflammatory model. Molecular docking studies revealed strong binding affinity with inflammatory cytokines and mediators such as TNF-α, IL-17, COX-2, and iNOS; further, they were quantified at the mRNA level by RT-PCR and ELISA analysis. Oral administration of TC significantly ameliorated paw edema, thymus and spleen indices, joint stiffness, thermal and flexion pain, C-reactive protein, RF, mobility, and stance of the treated animals. This therapeutic effectiveness was linked with a reduction in the mRNA expression of proinflammatory cytokines such as IL-1ß, IL-6, and IL-17. The findings of the reported research confirmed the effectiveness of TC in ameliorating joint stiffness and flexion pain by prominently lowering the inflammatory cytokines.

Design, synthesis, and in vitro and in silico studies of morpholine derived thiazoles as bovine carbonic anhydrase-II inhibitors.

Carbonic anhydrase CA-II enzyme is essential for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance due to its vital function within cellular processes. Herein, we screened 25 newly synthesized thiazole derivatives and assessed their inhibitory potential against the zinc-containing carbonic anhydrase CA-II enzyme. Intriguingly, derivatives of thiazole exhibited varying degrees of inhibitory action against CA-II. The distinctive attribute of these compounds is that they can attach to the CA-II binding site and block its action. Morpholine based thiazoles can be strategically modified to improve bovine CA-II inhibitor binding affinity, selectivity, and pharmacokinetics. Thiazole and morpholine moieties can boost inhibitory efficacy and selectivity over other calcium-binding proteins by interacting with target bovine CA-II binding sites. The derivatives 23-26 exhibited greater affinity when compared to the standard acetazolamide. Furthermore, kinetic study of the most potent compound 24 was performed, which exhibited concentration dependent inhibition with a K i value of 9.64 ± 0.007 µM. Molecular docking, MD simulation and QSAR analysis was also carried out to elucidate the interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, pharmacokinetic assessments showed that most of the compounds possess attributes conducive to potential drug development.

Management of COPD and Comorbidities in COPD patients by Dispensing Pharmaceutical Care following Global Initiative for chronic Obstructive Lung Disease-Guidelines (GOLD guidelines 2020): A study protocol for a Prospective Randomized Clinical Trial.

COPD (chronic obstructive pulmonary disease) is a medical condition that encompasses several chronic, progressive, and severe respiratory illnesses, such as emphysema and chronic bronchitis. COPD is the 4th most deadly disease in the world and its prevalence is expected to increase. Despite the abundance of information on the disease's etiology, pathophysiology, and treatment possibilities, it has long been underdiagnosed and underreported for a long time, particularly in developing countries. The symptoms of COPD result in significant impairments and significant impact on quality of life. COPD is the third leading cause of death in Pakistan. According to the published literature, COPD has been found to be associated with a serious economic burden, either the direct cost to healthcare systems in the form of frequent hospital admissions or indirect costs to patients suffering from COPD. Despite the availability of excellent medication, COPD treatment goals are frequently not achieved resulting in poor management of COPD. The recent studies revealed that due to the missing role of Pharmacists in most of the public sector hospitals of Pakistan, the COPD disease management protocols are not being properly followed. Pharmacists can help the healthcare system by implementing these management protocols that focus on patient education about the disease, prescribed medications, and proper inhalation techniques. Furthermore, the pharmacists as an effective healthcare's team member properly educate the patients about the ongoing assessments and their willingness to follow treatment recommendations and quit smoking, while referring them to smoking cessation programs as needed, following the GOLD guidelines. This aim of this clinical trial is to evaluate the impact of implementing standard treatment guidelines and the role of pharmacists in implementing GOLD guidelines for COPD management.

A novel MWCNT-encapsulated (2-aminoethyl)piperazine-decorated zinc(II) phthalocyanine composite: development of an electrochemical sensor for detecting the antipsychotic drug promazine in environmental samples.

A nanocomposite of (2-aminoethyl)piperazine ligand substituted with zinc(II) tetra carboxylic acid phthalocyanine (ZnTEPZCAPC) and MWCNTs was constructed and employed to develop an electrochemical sensor with outstanding sensitivity and a low detection limit. The macrocyclic complex ZnTEPZCAPC was first synthesized and then employed for the electrochemical determination of the antipsychotic drug promazine (PMZ). The as-prepared ZnTEPZCAPC and MWCNT nanocomposite was characterized using different techniques, such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), UV-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). Further, the prepared ZnTEPZCAPC@MWCNT nanocomposites were modified on a glassy carbon electrode (GCE) surface, and the electrochemical activity was investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CA) tests in pH 7.0 phosphate buffer solution (PBS) in the potential window of 0.0-1 V. The ZnTEPZCAPC@MWCNTs displayed a superior electrochemical performance because of their high electrochemical active surface area (0.453 cm2), good conductivity, and a synergetic effect. The developed electrochemical sensor exhibited a broad linear range of 0.05-635 µM and the lowest detection limit of 0.0125 nM, as well as excellent sensitivity, repeatability, and reproducibility. Finally, the fabricated sensor was successively used for the real-time detection of PMZ in environmental and biological samples and displayed feasible recoveries.

Phytotoxic responses of wheat to an imidazolium based ionic liquid in absence and presence of biochar.

Research on ionic liquids (ILs) and biochars (BCs) is a novel site of scientific interest. An experiment was designed to assess the effect of 1-propanenitrile imidazolium trifluoro methane sulfonate ([C2NIM][CF3SO3]) ionic liquid (IL) and IL-BC combination on the wheat plant. Three working standards of the IL; 50, 250, 500 and 1000 mg/L, prepared in deionized water, were tested in the absence and presence of BC on wheat seedling. Results indicated significant decrease in seed germination (%), length, fresh weight, chlorophyll a, b and carotenoid contents of wheat seedlings at 250, 500 and 1000 mg/L of the IL. An admirable increase in phenolic and 2,2-diphenyl-1-picrylhydrazyl (DPPH) contents of wheat seedlings was noted at 250, 500 and 1000 mg/L of the IL. The application of BC significantly ameliorated the negative effects of IL on the selected parameters of wheat. It is inferred that the undesirable effects of the IL on wheat growth can be positively restored by addition of BC.

Ex vivo fluorescence imaging for the identification of rhodamine-labeled bovine serum albumin and chitosan-coated gold and silver nanoparticles.

Therapeutic potential and toxic effects of in vivo administered gold nanoparticles (GNPs) and silver nanoparticles (SNP) depend on distribution in tissues. Rhodamine (Rho) labeled bovine serum albumin (BSA) and chitosan (Chi) were prepared by covalent conjugation and were characterized by fluorescence spectral analysis. GNP and SNP were coated with the labeled conjugates of BSA and chitosan by adsorption. The soluble Rho-BSA or Rho-Chi conjugates, uncoated, and conjugate-coated GNP, and SNP were orally administered into 8-week-old rats. After 24 h, rats were euthanized and the liver, kidney, spleen, and thymus were dissected. The tissues were examined ex vivo using a small animal in vivo imaging system. The liver, kidney, and thymus displayed higher fluorescence due to increased accumulation of Rho-BSA or Rho-Chi conjugate-coated nanoparticles (NPs) in the tissues as compared to the spleen where lower fluorescence was noticed. Tissues obtained from rats that were administered Rho-BSA or Rho-Chi conjugate-coated GNP and SNP showed tenfold higher fluorescence intensity as compared to tissues from rats that were given soluble conjugates or NP alone. The results strongly suggest significant tissue distribution of NP following oral administration.