Hymenaea courbaril resin-mediated gold nanoparticles as catalysts in organic dyes degradation and sensors in pharmaceutical pollutants.

In this study, green synthesis of gold nanoparticles (AuNPs) using aqueous extract from Hymenaea courbaril resin (HCR) is reported. The successful formation, functional group involvement, size, and morphology of the subject H. courbaril resin mediated gold nanoparticles (HCRAuNPs) were confirmed by Ultra Violet-Visible (UV-vis) spectroscopy, Fourier-Transform Infrared spectroscopy (FTIR), and Transmission Electron Microscopy (TEM) techniques. Stable and high yield of HCRAuNPs was formed in 1:15 (aqueous solution: salt solution) reacted in sunlight as indicated by the visual colour change and appearance of surface Plasmon resonance (SPR) at 560 nm. From the FT-IR results, the phenolic hydroxyl (-OH) functional group was found to be involved in synthesis and stabilization of nanoparticles. The TEM analysis showed that the particles are highly dispersed and spherical in shape with average size of 17.5 nm. The synthesized HCRAuNPs showed significant degradation potential against organic dyes, including methylene blue (MB, 85 %), methyl orange (MO, 90 %), congo red (CR, 83 %), and para nitrophenol (PNP, 76 %) up to 180 min. The nanoparticles also demonstrated the effective detection of pharmaceutical pollutants, including amoxicillin, levofloxacin, and azithromycin in aqueous environment as observable changes in color and UV-Vis spectral graph.

Hypoglycemic, anti-inflammatory, and neuroprotective potentials of crude methanolic extract from Acacia nilotica L. - results of an in vitro study.

Acacia nilotica L., also known as babul, belonging to the Fabaceae family and the Acacia genus, is typically used for ornamental purposes and also as a medicinal plant found in tropical and subtropical areas. This plant is a rich source of bioactive compounds. The current study aimed to elucidate the hypoglycemic, anti-inflammatory, and neuroprotective potential of A. nilotica's crude methanolic extract. The results of the in vitro antidiabetic assay revealed that methanolic extract of A. nilotica inhibited the enzyme α-glucosidase (IC50: 33 µg mL-1) and α-amylase (IC50: 17 µg mL-1) in a dose-dependent manner. While in the anticholinesterase enzyme inhibitory assay, maximum inhibition was shown by the extract against acetylcholinesterase (AChE) (637.01 µg mL-1) and butyrylcholinesterase (BChE) (491.98 µg mL-1), with the highest percent inhibition of 67.54% and 71.50% at 1000 µg mL-1, respectively. This inhibitory potential was lower as compared to the standard drug Galantamine that exhibited 82.43 and 89.50% inhibition at the same concentration, respectively. Moreover, the methanolic extract of A. nilotica also significantly inhibited the activities of cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) in a concentration-dependent manner. The percent inhibitory activity of 5-LOX and COX-2 ranged from 42.47% to 71.53% and 43.48% to 75.22%, respectively. Furthermore, in silico, in vivo, and clinical investigations must be planned to validate the above-stated bioactivities of A. nilotica.

Modulation in serum and hematological parameters as a prognostic indicator of COVID-19 infection in hypertension, diabetes mellitus, and different cardiovascular diseases.

SARS-CoV-2 infection affects and modulates serum as well as hematological parameters. However, whether it modifies these parameters in the existing disease conditions, which help in the erection of specific treatments for the disease, is under investigation. Here, we aimed to determine whether serum and hematological parameters alteration in various diseases, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD) and myocardial infarction (MI) conditions correlate and signal SARS-CoV-2 infection, which could be used as a rapid diagnosis tool for SARS-CoV-2 infection in disease conditions. To assess the projected goals, we collected blood samples of 1,113 male and female patients with solo and multiple disease conditions of DM/HTN/IHD/MI with severe COVID-19, followed by biochemical analysis, including COVID-19 virus detection by RT-qPCR. Furthermore, blood was collected from age-matched disease and healthy individuals 502 and 660 and considered as negative control. In our results, we examined higher levels of serum parameters, including D-dimer, ferritin, hs-CRP, and LDH, as well as hematological parameters, including TLC in sole and multiple diseases (DM/HTN/IHD/MI) conditions compared to the control subjects. Besides, the hematological parameters, including Hb, RBC, and platelet levels, decreased in the patients. In addition, we found declined levels of leukocyte count (%), lymphocyte (%), monocyte (%), and eosinophil (%), and elevated level of neutrophil levels (%) in all the disease patients infected with SARS-CoV-2. Besides, NLR and NMR ratios were also statistically significantly (p < 0.05) high in the patients with solo and multiple disease conditions of DM/HTN/IHD/MI infected with the SARS-CoV-2 virus. In conclusion, rapid alteration of sera and hematological parameters are associated with SARS-CoV-2 infections, which could help signal COVID-19 in respective disease patients. Moreover, our results may help to improve the clinical management for the rapid diagnosis of COVID-19 concurrent with respective diseases.

The interaction between formylphenoxyacetic acid derivatives (chalcone and flavones) and ionic surfactants: Insights into binding constants, solubilisation and physiochemical properties.

In this study, UV-vis spectroscopy was employed to investigate the interaction between formylphenoxyacetic acid (FPAA) and its derivatives (chalcone and flavones) with ionic surfactants (SDS, CTAB, and DTAB) in different physiological environments. Changes in the physiochemical properties of FPAA chalcone and flavones including binding constants, partitioning constants, and Gibbs free energy were observed which were influenced by the presence of ionic surfactants computed using mathematical models. The solubilization of the targeted compounds in the ionic surfactants was determined through the binding constant (Kb). The results of the present study indicated that electrostatic interactions played a significant role in the solubilization of the targeted compounds in SDS, CTAB, and DTAB. At pH 4.1, FPAA chalcone exhibited stronger binding affinity with SDS compared to CTAB and DTAB. However, at pH 7.4, chalcone showed stronger binding with DTAB compared to SDS, while negligible interaction with CTAB was observed at pH 7.4. The flavones demonstrated stronger binding with DTAB at pH 7.4 compared to SDS and CTAB and it exhibited strong bonding with CTAB at pH 4.1. The negative values of the Gibbs free energy for binding (ΔGb˚) and partitioning (ΔGp˚) constants displayed the spontaneity of the process. However, FPAA chalcone with SDS and FPAA flavones with DTAB furnished positive ΔGb˚, indicating a non-spontaneous process.

Evaluation of Habenaria aitchisonii Reichb. for antioxidant, anti-inflammatory, and antinociceptive effects with in vivo and in silico approaches.

Habenaria aitchisonii Reichb was analyzed in this research, including its chemical composition and its in vitro antioxidant, anti-inflammatory, acute oral toxicity, and antinociceptive activity. The chloroform and ethyl acetate fractions were found to be the most powerful based on in vitro antioxidant, anti-inflammatory, and analgesic assays. The acute oral toxicity of the crude methanolic extract was determined before in vivo studies. The acetic acid and formalin tests were used to measure the antinociceptive effect, and the potential mechanisms involved in antinociception were explored. The carrageenan-induced paw edema test was used to examine the immediate anti-inflammatory effect, and many phlogistic agents were used to determine the specific mechanism. Furthermore, for ex vivo activities, the mice were sacrificed, the forebrain was isolated, and the antioxidant levels of glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and catalase (CAT) were estimated using a UV spectrophotometer. No toxicity was seen at oral dosages up to 3,000 mg/kg. The antinociceptive impact was much higher than the standard drug. Both the inflammatory and neurogenic phases of the formalin experiment revealed an analgesic effect in the chloroform and ethyl acetate fractions. In carrageenan anti-inflammatory assays, the chloroform fraction (Ha.Chf) was the most potent fraction. We further studied the GC-MS of crude plant extract and found a total of 18 compounds. In the anti-inflammatory mechanism, it was observed that the Ha.Chf inhibits the COX-2 as well as 5-LOX pathways. The results exhibited that this species is a good source of phytocomponents like germacrone, which can be employed as a sustainable and natural therapeutic agent, supporting its traditional use in folk medicine for inflammatory conditions and pain.

Phenolic phytochemistry, in vitro, in silico, in vivo, and mechanistic anti-inflammatory and antioxidant evaluations of Habenaria digitata.

Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 µg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 µg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress.

Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies.

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a-5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05 µM), exhibiting IC50 values in the range of 0.76-9.01 µM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32 µM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 µM, respectively. Standard zileuton exhibited an IC50 value of 11.00 µM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.

Exploitation of the multitarget role of new ferulic and gallic acid derivatives in oxidative stress-related Alzheimer's disease therapies: design, synthesis and bioevaluation.

Monoamine oxidases (MAOs) inhibitors could decrease reactive oxygen species (ROS) generation, enhance mono-aminergic neural transmission, and have major therapeutic benefits for the treatment of Alzheimer's disease (AD). Following the conjunction of ferulic acid (FA)/gallic acid (GA) with sulfonamide, alanine and 2-aminobenzothiazole, we planned to assess the radical scavenging and antioxidant properties of synthesized analogs by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. GA analog 28 was identified as the most potent antioxidant compound with IC50 values of 1.77 µM and 2.06 µM in DPPH and ABTS assays respectively. In the in vitro enzyme inhibition assays, synthesized derivative 23 emerged as a potent multitarget inhibitor of hMAO-B, eeAChE. COX-2 and 5-LOX with IC50 values of 0.037 µM, 0.071 µM, 14.3 µM and 0.59 µM, respectively. Moreover, selected compounds 23, 25, 26 and 28 displayed good to moderate inhibition of self-mediated amyloid ß1-42 peptide aggregation. More importantly, compounds 23, 25, 28 and 29 showed no neurotoxicity on SH-SY5Y cells and also showed excellent neuroprotective effects against H2O2-induced SH-SY5Y cells. In the in vivo experiment, antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) were studied in the brain of male BALB/c mice at the dose of 5 mg kg-1. All the tested compounds, except 29, have shown good to in vivo antioxidant potential. Docking studies on 3D crystallographic structures of AChE and MAO-B showed significant interactions with catalytic amino acid residues. In conclusion, the current study showed that FA/GA derivatives could be further exploited for their multitarget role in oxidative stress-related AD therapies.

Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum ß-lactamase- and carbapenemase-producing bacteria.

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum ß-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.

Investigation of anti-nociceptive, anti-inflammatory potential and ADMET studies of pure compounds isolated from Isodon rugosus Wall. ex Benth.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77 µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead to inflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Optimization of Kidney Health in Liver Transplant Candidates: Pretransplant Considerations and Modalities.

Patients with decompensated end-stage liver disease (ESLD) are at increased risk for mortality, and only liver transplantation (LT) offers meaningful hope for survival. These patients are at risk for kidney dysfunction through the continuum of care for ESLD including LT. We discuss the role of accurate estimation and measurement of baseline glomerular filtration rate in assessment of kidney dysfunction among those with ESLD. Optimizing kidney function is a vital goal in the management of these patients before LT. In this review, we summarize salient aspects of assessing and optimizing kidney function in this patient population. Precipitating factors and different causes of acute kidney injury are discussed, including hepatorenal syndrome. We further review treatment options for acute kidney injury including volume management. The role of vasopressor therapy, renal replacement therapy, and transjugular intrahepatic portosystemic shunting are discussed.

Drug repurposing of FDA-approved anti-viral drugs via computational screening against novel 6M03 SARS-COVID-19.

OBJECTIVE: The COVID-19 pandemic has been recognized as severe acute respiratory syndrome, one of the worst and disastrous infectious diseases in human history. Until now, there is no cure to this contagious infection although some multinational pharmaceutical companies have synthesized the vaccines and injecting them into humans, but a drug treatment regimen is yet to come. AIM: Among the multiple areas of SARS-CoV-2 that can be targeted, protease protein has significant values due to its essential role in viral replication and life. The repurposing of FDA-approved drugs for the treatment of COVID-19 has been a critical strategy during the pandemic due to the urgency of effective therapies. The novelty in this work refers to the innovative use of existing drugs with greater safety, speed, cost-effectiveness, broad availability, and diversity in the mechanism of action that have been approved and developed for other medical conditions. METHODS: In this research work, we have engaged drug reprofiling or drug repurposing to recognize possible inhibitors of protease protein 6M03 in an instantaneous approach through computational docking studies. RESULTS: We screened 16 FDA-approved anti-viral drugs that were known for different viral infections to be tested against this contagious novel strain. Through these reprofiling studies, we come up with 5 drugs, namely, Delavirdine, Fosamprenavir, Imiquimod, Stavudine, and Zanamivir, showing excellent results with the negative binding energies in Kcal/mol as - 8.5, - 7.0, - 6.8, - 6.8, and - 6.6, respectively, in the best binding posture. In silico studies allowed us to demonstrate the potential role of these drugs against COVID-19. CONCLUSION: In our study, we also observed the nucleotide sequence of protease protein consisting of 316 amino acid residues and the influence of these pronouncing drugs over these sequences. The outcome of this research work provides researchers with a track record for carrying out further investigational procedures by applying docking simulations and in vitro and in vivo experimentation with these reprofile drugs so that a better drug can be formulated against coronavirus.

2-Hydroxybenzohydrazide as a novel potential candidate against nociception, inflammation, and pyrexia: in vitro, in vivo, and computational approaches.

The current study was designed to evaluate the 2-hydroxybenzohydrazide (HBH) as a drug having efficacy against pyrexia, inflammation, and nociception. Besides, the therapeutic effects of HBH on oxidative stress and C-reactive proteins were also evaluated. The pharmacological studies on HBH (20-60 mg/kg) were conducted using nociception, inflammation, and pyrexia standard models. Naloxone antagonism was performed to assess the possible involvement of opioidergic mechanisms. The antioxidant study was conducted on ABTS and DPPH assays using gallic acid as a standard. Moreover, the binding capability of HBH with enzymes cyclooxygenase-I/II (COX-I/II) was determined using molecular modeling analysis. The findings indicated that the HBH dose-dependently inhibited pain, inflammation, and pyrexia. The HBH has significant anti-nociceptive and anti-inflammatory activities at 60 mg/kg (***p < 0.001), similar to the lower doses of diclofenac sodium (50 mg/kg) and tramadol (30 mg/kg). The HBH at 60 mg/kg reduced pyrexia as paracetamol (150 mg/kg). The HBH at 20-60 mg/kg doses declined the plasma C-reactive protein concentration. The mechanistic studies showed that the anti-nociceptive effect of HBH was antagonized by naloxone, indicating that the opioidergic mechanisms are involved. Furthermore, computational studies showed that the HBH exhibited an affinity for COX-I/II target receptors. The HBH significantly inhibited ABTS and DPPH radicals (IC50 = 33.81 and 26.74 µg/ml). These results proposed that the HBH has significant antipyretic, anti-inflammatory, and anti-nociceptive activities involving opioidergic mechanism.

Unlocking green innovation and environmental performance: the mediated moderation of green absorptive capacity and green innovation climate.

This study extends the foundations of the natural resource-based view (NRBV) by introducing a mediation-moderation framework by analyzing the influence of green intellectual capital (GIC) on both green innovation performance (GIP) and environmental performance (EP) while simultaneously considering the mediating role of green absorptive capacity (GAC) and the moderating influence of the green innovation climate (GICL). The data for this study was gathered from a sample of 575 participants employed within small and medium enterprises' (SMEs') manufacturing firms. This dataset was utilized to evaluate the proposed model; this study uses the PLS-SEM approach to comprehensively examine the complex interactions among these variables. This model adds to the theoretical understanding of NRBV and enhances its practical applicability. The findings of this study reveal a positive relationship between GIC, GAC, GIP, and EP within organizations. Furthermore, our investigation reveals a positive correlation between a GICL and the relationships involving GIC, GAC, GIP, and EP. Importantly, this research introduces a novel perspective by clarifying the complex relations among these variables and highlighting the positive correlation between a GICL and the relationships involving GIC, GAC, GIP, and EP. This novel approach enhances the theoretical understanding of NRBV and its practical applicability in fostering GIP and EP within manufacturing SMEs operating in Pakistan.

Eco-friendly approach for the determination of moxifloxacin in pharmaceutical formulations and biological fluids based on fluorescence quenching of l-tryptophan.

A rapid, novel and cost-effective spectrofluorimetric method developed to determine moxifloxacin (MFX) in pharmaceutical preparations because MFX in a pH 10 medium could reduce the fluorescence intensity of l-tryptophan. The maximum fluorescence excitation and emission wavelengths were found to be 280 and 363 nm respectively. A range of factors affecting fluorescence quenching and the effect of co-existing substances were investigated. Fluorescence quenching values (ΔF = FL-tryptophan - FMoxi-L-tryptophan ) displayed a strong linear relationship with the MFX concentration ranging from 0.2 to 8.0 µg/ml under optimum conditions. The limit of detection was found to be 6.1 × 10-4  µg/ml. The proposed method was shown to be suitable for MFX determination in pharmaceutical tablets and biological fluids by the linearity, recovery and limit of detection. The spectrofluorimetric approach that has been developed is extremely eco-friendly, as evidenced by the fact that all the experimental components and solvents were safe for the environment.

Antioxidant, carbonic anhydrase inhibition and diuretic activity of Leptadenia pyrotechnica Forssk. Decne.

Background: Leptadenia pyrotechnica Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of L. pyrotechnica in nephrolithiasis, kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of L. pyrotechnica as diuretic. Methods: The 70 % methanolic L. pyrotechnica (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition. Results: Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways. Conclusion: L. pyrotechnica contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.

Study protocol for "In-vehicle sensors to detect changes in cognition of older drivers".

BACKGROUND: Driving is a complex behavior that may be affected by early changes in the cognition of older individuals. Early changes in driving behavior may include driving more slowly, making fewer and shorter trips, and errors related to inadequate anticipation of situations. Sensor systems installed in older drivers' vehicles may detect these changes and may generate early warnings of possible changes in cognition. METHOD: A naturalistic longitudinal design is employed to obtain continuous information on driving behavior that will be compared with the results of extensive cognitive testing conducted every 3 months for 3 years. A driver facing camera, forward facing camera, and telematics unit are installed in the vehicle and data downloaded every 3 months when the cognitive tests are administered. RESULTS: Data processing and analysis will proceed through a series of steps including data normalization, adding information on external factors (weather, traffic conditions), and identifying critical features (variables). Traditional prediction modeling results will be compared with Recurring Neural Network (RNN) approach to produce Driver Behavior Indices (DBIs), and algorithms to classify drivers within age, gender, ethnic group membership, and other potential group characteristics. CONCLUSION: It is well established that individuals with progressive dementias are eventually unable to drive safely, yet many remain unaware of their cognitive decrements. Current screening and evaluation services can test only a small number of individuals with cognitive concerns, missing many who need to know if they require treatment. Given the increasing number of sensors being installed in passenger vehicles and pick-up trucks and their increasing acceptability, reconfigured in-vehicle sensing systems could provide widespread, low-cost early warnings of cognitive decline to the large number of older drivers on the road in the U.S. The proposed testing and evaluation of a readily and rapidly available, unobtrusive in-vehicle sensing system could provide the first step toward future widespread, low-cost early warnings of cognitive change for this large number of older drivers in the U.S. and elsewhere.

Novel Coumarin Derivatives as Potential Urease Inhibitors for Kidney Stone Prevention and Antiulcer Therapy: From Synthesis to In Vivo Evaluation.

The presence of ammonium ions in urine, along with basic pH in the presence of urease-producing bacteria, promotes the production of struvite stones. This causes renal malfunction, which is manifested by symptoms such as fever, nausea, vomiting, and blood in the urine. The involvement of urease in stone formation makes it a good target for finding urease enzyme inhibitors, which have the potential to be developed as lead drugs against kidney stones in the future. The documented ethnopharmacology of coumarin 2-one against bacterial, fungal and viral strains encouraged us to synthesize new derivatives of coumarins by reacting aromatic aldehydes with 4-aminocoumarin. The synthesized compounds (2a to 11a) were evaluated for their antimicrobial, in vitro, and in silico properties against the urease enzyme. The study also covers in vivo determination of the synthesized compounds with respect to different types of induced ulcers. The molecular docking study along with extended MD simulations (100 ns each) and MMPBSA study confirmed the potential inhibitory candidates as evident from computed ∆Gbind (3a = -11.62 and 5a = -12.08 Kcal/mol) against the urease enzyme. The in silico analyses were augmented by an enzymatic assay, which revealed that compounds 3a and 5a had strong inhibitory action, with IC50 of 0.412 µM (64.0% inhibition) and 0.322 µM (77.7% inhibition), respectively, compared to standard (Thiourea) with 82% inhibition at 0.14 µM. Moreover, the most active compound, 5a, was further tested in vivo for antiulcer activity by different types of induced ulcers, including pyloric ligation-, ethanol-, aspirin-, and histamine-induced ulcers. Compound 5a effectively reduced gastric acidity, lipid peroxidation, and ulceration in a rat model while also inhibiting gastric ATPase activity, which makes it a promising candidate for ulcer treatment. As a result of the current research, 3a and 5a may be used as new molecules for developing potent urease inhibitors. Additionally, the compound 3a showed antibacterial activity against Staphylococcus aureus and Salmonella typhimurium, with zones of inhibition of 41 ± 0.9 mm and 35 ± 0.9 mm, respectively. Compound 7a showed antibacterial activity against Staphylococcus aureus and Salmonella typhimurium, with zones of inhibition of 30 ± 0.8 mm and 42 ± 0.8 mm, respectively. These results prove that the synthesized compounds also possess good antibacterial potential against Gram-positive and Gram-negative bacterial strains.

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives.

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6, C5, and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 (C7). Compound 1 (C1) and Compound 2 (C2) were found to cross the blood-brain barrier (BBB). Lipinski's rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2, C5, C6, C7, and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7. The medicinal chemistry of all the compounds C1-C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future.