Copper-Vit B3 MOF preparation, characterization and catalytic evaluation in a one-pot synthesis of benzoxanthenones with docking validation as anti H. pylori.

Copper-Vit B3 MOF was successfully prepared by efficient and eco hydrothermal method. The prepared MOF was characterized as a tetragonal crystal copper-MOF nanoparticles by FTIR, SEM, TEM, EDX and XRD. The prepared nanoparticles were used as an effective, inexpensive and low-toxic catalyst in the one-pot synthesis of some new benzoxanthenone derivatives. As example 4-(9,9-dimethyl-11-oxo-8,10,11,12-tetrahydro-9H-benzo[a]xanthen-12-yl)phenyl benzoate (4h) was synthesized in high yield 92%. The MOF catalyst's role is activating the nucleophilic attack by increasing the carbonyl polarization, and this generally improves the reaction time, which ranges between 20-60 minutes and products' yields ranging between 80-92%. Prepared compounds (4a-4j) undergo molecular docking scanning as Helicobacter pylori type II dehydroquinase inhibitors, and the data obtained showed that there are three promises of the prepared compounds 4d, 4e, 4h and 4j compared with amoxicillin.

ComPRePS: An Automated Cloud-based Image Analysis tool to democratize AI in Digital Pathology.

Artificial intelligence (AI) has extensive applications in a wide range of disciplines including healthcare and clinical practice. Advances in high-resolution whole-slide brightfield microscopy allow for the digitization of histologically stained tissue sections, producing gigapixel-scale whole-slide images (WSI). The significant improvement in computing and revolution of deep neural network (DNN)-based AI technologies over the last decade allow us to integrate massively parallelized computational power, cutting-edge AI algorithms, and big data storage, management, and processing. Applied to WSIs, AI has created opportunities for improved disease diagnostics and prognostics with the ultimate goal of enhancing precision medicine and resulting patient care. The National Institutes of Health (NIH) has recognized the importance of developing standardized principles for data management and discovery for the advancement of science and proposed the Findable, Accessible, Interoperable, Reusable, (FAIR) Data Principles1 with the goal of building a modernized biomedical data resource ecosystem to establish collaborative research communities. In line with this mission and to democratize AI-based image analysis in digital pathology, we propose ComPRePS: an end-to-end automated Computational Renal Pathology Suite which combines massive scalability, on-demand cloud computing, and an easy-to-use web-based user interface for data upload, storage, management, slide-level visualization, and domain expert interaction. Moreover, our platform is equipped with both in-house and collaborator developed sophisticated AI algorithms in the back-end server for image analysis to identify clinically relevant micro-anatomic functional tissue units (FTU) and to extract image features.

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer's, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions.

In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a-f, 6a-f, and 7a-f, to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer's, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a-f, 6a-f, and 7a-f showed that the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d, 5e, and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.

ComPRePS: An Automated Cloud-based Image Analysis tool to democratize AI in Digital Pathology.

Artificial intelligence (AI) has extensive applications in a wide range of disciplines including healthcare and clinical practice. Advances in high-resolution whole-slide brightfield microscopy allow for the digitization of histologically stained tissue sections, producing gigapixel-scale whole-slide images (WSI). The significant improvement in computing and revolution of deep neural network (DNN)-based AI technologies over the last decade allow us to integrate massively parallelized computational power, cutting-edge AI algorithms, and big data storage, management, and processing. Applied to WSIs, AI has created opportunities for improved disease diagnostics and prognostics with the ultimate goal of enhancing precision medicine and resulting patient care. The National Institutes of Health (NIH) has recognized the importance of developing standardized principles for data management and discovery for the advancement of science and proposed the Findable, Accessible, Interoperable, Reusable, (FAIR) Data Principles1 with the goal of building a modernized biomedical data resource ecosystem to establish collaborative research communities. In line with this mission and to democratize AI-based image analysis in digital pathology, we propose ComPRePS: an end-to-end automated Computational Renal Pathology Suite which combines massive scalability, on-demand cloud computing, and an easy-to-use web-based user interface for data upload, storage, management, slide-level visualization, and domain expert interaction. Moreover, our platform is equipped with both in-house and collaborator developed sophisticated AI algorithms in the back-end server for image analysis to identify clinically relevant micro-anatomic functional tissue units (FTU) and to extract image features.

In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives.

There is a need for new pharmaceutical discoveries from bioactive nitrogenous derivatives due to the emergence of scourges, numerous pandemics, and diverse health problems. In this context, pyrazolo[1,5-a]pyrimidine derivatives 12a and 12b were synthesized and screened to evaluate their biological potentials in vitro as antioxidants, anti-diabetics, anti-Alzheimer's, anti-arthritics, and anti-cancer agents. Additionally, the computational pharmacokinetic and toxicity properties of the two pyrazolo[1,5-a]pyrimidines 12a and 12b were calculated and analyzed. The preliminary studies and results of this work represent the initial steps toward more advanced studies and define the bioactive chemical structure of pyrazolo[1,5-a]pyrimidine derivatives with the goal of exploring new drugs to address numerous health problems.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents.

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7-9, 11-13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

Using Selenium-enriched Mutated Probiotics as Enhancer for Fertility Parameters in Mice.

Increasing fertility rates have become one of the factors that concern all people in the world. Therefore, the study aims to use two mutated strains of probiotics enriched with selenium (PSe40/60/1 and BSe50/20/1) to improve fertility. Thirty Swiss albino male mice were divided into three groups; control, LP + S was given Lactobacillus plantarum PSe40/60/1 plus selenium, and BL + S was given Bifidobacterium longum BSe50/20/1 plus selenium. Free testosterone, LH, and FSH were measured in serum by biochemical analysis. Testicular tissues were examined by histopathological analysis. The count and motility of sperm, and sperm abnormalities were determined by microscopic examination. The method of qRT-PCR was used to detect gene expression of Tspyl1, Hsd3b6, and Star genes. The biochemical results showed that serum content of free testosterone (FT) hormone had significantly increase in the BL + S and LP + S groups compared with control. Levels of LH and FSH hormones were the highest in the BL + S group. The treated groups showed all developmental stages of spermatogenesis, including spermatogenesis, spermatocytes, and seminiferous tubule spermatids, as well as intact Sertoli cells and Leydig cells without changes. When compared to the control group, sperm count and motility increased in the BL + S group, while sperm abnormalities decreased. The expression of Tspyl1 gene in testicular tissues decreased in the LP + S and BL + S groups, while the expression of Star and Hsd3b6 genes was higher in the BL + S group and lower in the LP + S group compared with the control group. Therefore, Bifidobacterium longum BSe50/20/1 enriched with selenium could be useful in enhancing male fertility.

Potentiometric planar platforms modified with a multiwalled carbon nanotube/polyaniline nanocomposite and based on imprinted polymers for erythromycin assessment.

A screen-printed potentiometric sensor for the erythromycin macrolide antibiotic (ERY) that is affordable, highly selective, and sensitive is made, described, and used for drug monitoring. Two circular carbon dots with a diameter of 4 mm make up the sensor. Multiwalled carbon nanotubes and polyaniline (f-MWCNTs/PANi) nanocomposites are used to change one carbon spot, which is then used as an ion-to-electron transfer material. Ag/AgCl is applied to the other spot, which is then used as a reference electrode. A solid-state polyvinyl butyral (PVB) is placed onto the second carbon spot to work as a reference electrode, and an ERY molecularly imprinted drug polymer (MIP) is coated onto the f-MWCNTs/PANi-containing strip to serve as a drug identification sensing material. Chronopotentiometry (CP) is used to analyze the integrated sensor's performance characteristics. It is confirmed that f-MWCNTs/PANi has an increased impact on the potential stability as well as the sensing membrane's interfacial double-layer capacitance. At a detection limit of 9.6 ± 0.4 × 10-7 M, the developed sensor exhibits a Nernstian slope of 54.0 ± 0.5 mV per decade (R2 = 0.9994) over the linear range of 4.6 × 10-6 to 1.0 × 10-3 M. When exposed to different related substances such azithromycin, clarithromycin, dirithromycin, paracetamol, and ascorbic acid, the sensor exhibits excellent selectivity. For the direct potentiometric determination of ERY in some pharmaceutical formulations and in samples of spiked human urine, the assay method has been validated and shown to be adequate. The obtained recovery ranges from 93.0 ± 0.5 to 104.3 ± 0.7 of the nominal or spiked concentration, with a mean relative standard deviation of ±0.6%. Due to the near closeness of the responsive membrane and the liquid junction, the use of all-solid-state electrodes coupled with a planar disposable platform enables applications with a minimum sample volume. The effectiveness of the suggested sensor in a complex urine matrix points to its use in hospitals for quick overdose patient detection as well as for quality control/quality assurance tests in the pharmaceutical sector.

QSAR-driven screening uncovers and designs novel pyrimidine-4,6-diamine derivatives as potent JAK3 inhibitors.

This study presents a robust and integrated methodology that harnesses a range of computational techniques to facilitate the design and prediction of new inhibitors targeting the JAK3/STAT pathway. This methodology encompasses several strategies, including QSAR analysis, pharmacophore modeling, ADMET prediction, covalent docking, molecular dynamics (MD) simulations, and the calculation of binding free energies (MM/GBSA). An efficacious QSAR model was meticulously crafted through the employment of multiple linear regression (MLR). The initial MLR model underwent further refinement employing an artificial neural network (ANN) methodology aimed at minimizing predictive errors. Notably, both MLR and ANN exhibited commendable performance, showcasing R2 values of 0.89 and 0.95, respectively. The model's precision was assessed via leave-one-out cross-validation (CV) yielding a Q2 value of 0.65, supplemented by rigorous Y-randomization. , The pharmacophore model effectively differentiated between active and inactive drugs, identifying potential JAK3 inhibitors, and demonstrated validity with an ROC value of 0.86. The newly discovered and designed inhibitors exhibited high inhibitory potency, ranging from 6 to 8, as accurately predicted by the QSAR models. Comparative analysis with FDA-approved Tofacitinib revealed that the new compounds exhibited promising ADMET properties and strong covalent docking (CovDock) interactions. The stability of the new discovered and designed inhibitors within the JAK3 binding site was confirmed through 500 ns MD simulations, while MM/GBSA calculations supported their binding affinity. Additionally, a retrosynthetic study was conducted to facilitate the synthesis of these potential JAK3/STAT inhibitors. The overall integrated approach demonstrates the feasibility of designing novel JAK3/STAT inhibitors with robust efficacy and excellent ADMET characteristics that surpass Tofacitinib by a significant margin.Communicated by Ramaswamy H. Sarma.

Paper-Based Analytical Device Based on Potentiometric Transduction for Sensitive Determination of Phenobarbital.

In medicine, barbiturates are a class of depressive medications used as hypnotics, anticonvulsants, and anxiolytics. For the treatment of specific forms of epilepsy and seizures in young children in underdeveloped countries, the World Health Organization recommends phenobarbital (PBAR), a barbiturate drug. This review describes the fabrication and characterization of a paper-based analytical apparatus for phenobarbital detection that is straightforward, affordable, portable, and disposable. All of the solid-state ion-selective electrodes (ISEs) for PBAR as well as a Ag/AgCl reference electrode were constructed and optimized on a nonconductive paper substrate. Using carbon nanotube ink, the sensors were made to function as an ion-to-electron transducer and to make the paper conductive. A suitable polymeric membrane is drop-cast onto the surface of the carbon ink orifice. The pyrido-tetrapeptide and pyrido-hexapeptide derivatives, which were recently synthesized, functioned as distinct ionophores in the PBAR-membrane sensor, enabling its detection. With a detection limit of 5.0 × 10-7 M, the manufactured analytical device demonstrated a Nernstian response to PBAR anions in 50 mM phosphate buffer, pH 8.5, over a linear range of 1.0 × 10-6 to 1.0 × 10-3 M. The PBAR-based sensors showed quick (less than 5 s) response times for PBAR ion detection. The modified separate solution method was utilized to evaluate the selectivity pattern of these novel ionophores with respect to PBAR ions in comparison to other common anions. The analytical instrument that was exhibited on paper had good precision both within and between days. The suggested technology assisted in the detection of trace amounts of PBAR in real pharmaceutical samples. A comparison was made between the data acquired using the HPLC reference method and the information obtained by the recommended potentiometric approach. The described paper-based analytical device may be a good choice for point-of-care PBAR determination because it is cheap and easy to find and can self-pump (especially when combined with potentiometric detection).

Nanoparticles of a Pyrazolo-Pyridazine Derivative as Potential EGFR and CDK-2 Inhibitors: Design, Structure Determination, Anticancer Evaluation and In Silico Studies.

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Phytochemical Analysis, In Vitro Biological Activities, and Computer-Aided Analysis of Potentilla nepalensis Hook Compounds as Potential Melanoma Inhibitors Based on Molecular Docking, MD Simulations, and ADMET.

Potentilla nepalensis Hook is a perennial Himalayan medicinal herb of the Rosaceae family. The present study aimed to evaluate biological activities such as the antioxidant, antibacterial, and anticancer activities of roots and shoots of P. nepalensis and its synergistic antibacterial activity with antibacterial drugs. Folin-Ciocalteau and aluminium chloride methods were used for the calculation of total phenolic (TPC) and flavonoid content (TFC). A DPPH radical scavenging assay and broth dilution method were used for the determination of the antioxidant and antibacterial activity of the root and shoot extracts of P. nepalensis. Cytotoxic activity was determined using a colorimetric MTT assay. Further, phytochemical characterization of the root and shoot extracts was performed using the Gas chromatography-mass spectrophotometry (GC-MS) method. The TPC and TFC were found to be higher in the methanolic root extract of P. nepalensis. The methanolic shoot extract of P. nepalensis showed good antioxidant activity, while then-hexane root extract of P. nepalensis showed strong cytotoxic activity against tested SK-MEL-28 cells. Subsequently, in silico molecular docking studies of the identified bioactive compounds predicted potential anticancer properties. This study can lead to the production of new herbal medicines for various diseases employing P. nepalensis, leading to the creation of new medications.

Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction.

Introduction: Cadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats. Methods: In total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days. Results: Exposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats. Conclusion: Thus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats.

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors.

Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 µM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC50 9.45±0.05 µM followed by 3 e (IC50 22.52±0.15 µM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

Scale-adaptive model for detection and grading of age-related macular degeneration from color retinal fundus images.

Age-related Macular Degeneration (AMD), a retinal disease that affects the macula, can be caused by aging abnormalities in number of different cells and tissues in the retina, retinal pigment epithelium, and choroid, leading to vision loss. An advanced form of AMD, called exudative or wet AMD, is characterized by the ingrowth of abnormal blood vessels beneath or into the macula itself. The diagnosis is confirmed by either fundus auto-fluorescence imaging or optical coherence tomography (OCT) supplemented by fluorescein angiography or OCT angiography without dye. Fluorescein angiography, the gold standard diagnostic procedure for AMD, involves invasive injections of fluorescent dye to highlight retinal vasculature. Meanwhile, patients can be exposed to life-threatening allergic reactions and other risks. This study proposes a scale-adaptive auto-encoder-based model integrated with a deep learning model that can detect AMD early by automatically analyzing the texture patterns in color fundus imaging and correlating them to the vasculature activity in the retina. Moreover, the proposed model can automatically distinguish between AMD grades assisting in early diagnosis and thus allowing for earlier treatment of the patient's condition, slowing the disease and minimizing its severity. Our model features two main blocks, the first is an auto-encoder-based network for scale adaption, and the second is a convolutional neural network (CNN) classification network. Based on a conducted set of experiments, the proposed model achieves higher diagnostic accuracy compared to other models with accuracy, sensitivity, and specificity that reach 96.2%, 96.2%, and 99%, respectively.

Anti-inflammatory activity of novel derivatives of pyrazolo [3,4d] pyridazine against digestive system inflammation.

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation.

Acid protease functionalized novel silver nanoparticles (APTs-AgNPs): A new approach towards photocatalytic and biological applications.

Herein, we described for the first time, an efficient biogenic synthesis of APTs-AgNPs using acid protease from Melilotus indicus leaf extract. The acid protease (APTs) has an essential role in the stabilization, reduction, and capping of APTs-AgNPs. The crystalline nature, size, and surface morphology of APTs-AgNPs were examined using different techniques such as XRD, UV, FTIR, SEM, EDS, HRTEM, and DLS analysis. The generated APTs-AgNPs demonstrated notable performance as dual functionality (photocatalyst and antibacterial disinfection). By destroying 91 % of methylene blue (MB) in <90 min of exposure, APTs-AgNPs demonstrated remarkable photocatalytic activity. APTs-AgNPs also showed remarkable stability as a photocatalyst after five test cycles. Furthermore, the APTs-AgNPs was found to be a potent antibacterial agent with inhibition zones of 30(±0.5 mm), 27(±0.4 mm), 16(±0.1 mm), and 19(±0.7 mm) against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, respectively, under both light and dark conditions. Furthermore, APTs-AgNPs effectively scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, demonstrating their potent antioxidant activity. The outcomes of this study thus demonstrates the dual functionality of APTs-AgNPs produced using the biogenic approach method as a photocatalyst and an antibacterial agent for effective microbial and environmental control.

Point-of-care paper-based analytical device for potentiometric detection of myoglobin as a cardiovascular disease biomarker.

One of the cardiac biomarkers, myoglobin (Mb), is important in the rapid identification of cardio-vascular disorders. Therefore, point-of-care monitoring is essential. Pursuing this goal, a robust, reliable, and affordable paper-based analytical apparatus for potentiometric sensing has been developed and characterized. The molecular imprint technique was used to create a customized biomimetic antibody for myoglobin (Mb) on the surface of carboxylated multiwalled carbon nanotubes (MWCNT-COOH). This was accomplished by attaching Mb to carboxylated MWCNTs' surfaces and then filling the empty spaces through the mild polymerization of acrylamide in N,N-methylenebisacrylamide and ammonium persulphate. The modification of the MWCNTs' surface was verified by SEM and FTIR analysis. A hydrophobic paper substrate coated with fluorinated alkyl silane (CF3(CF2)7CH2CH2SiCl3, CF10) has been coupled with a printed all-solid-state Ag/AgCl reference electrode. The presented sensors showed a linear range of 5.0 × 10-8 to 1.0 × 10-4 M with a potentiometric slope of -57.1 ± 0.3 mV decade-1 (R2 = 0.9998) and a detection limit of 28 nM at pH 4. Compared to creatinine, sucrose, fructose, galactose, sodium glutamate, thiamine, alanine, ammonium, uric acid, albumin, glutamine, guanine, troponine T, and glucose, the sensor showed good selectivity for Mb. It demonstrated a good recovery for the detection of Mb in several fake serum samples (93.0-103.3%), with an average relative standard deviation of 4.5%. The current approach might be viewed as a potentially fruitful analytical tool for obtaining disposable, cost-effective paper-based potentiometric sensing devices. These types of analytical devices can be potentially manufacturable at large scales in clinical analysis.