Mathematical modeling and dynamics of immunological exhaustion caused by measles transmissibility interaction with HIV host.

This paper mainly addressed the study of the transmission dynamics of infectious diseases and analysed the effect of two different types of viruses simultaneously that cause immunodeficiency in the host. The two infectious diseases that often spread in the populace are HIV and measles. The interaction between measles and HIV can cause severe illness and even fatal patient cases. The effects of the measles virus on the host with HIV infection are studied using a mathematical model and their dynamics. Analysing the dynamics of infectious diseases in communities requires the use of mathematical models. Decisions about public health policy are influenced by mathematical modeling, which sheds light on the efficacy of various control measures, immunization plans, and interventions. We build a mathematical model for disease spread through vertical and horizontal human population transmission, including six coupled nonlinear differential equations with logistic growth. The fundamental reproduction number is examined, which serves as a cutoff point for determining the degree to which a disease will persist or die. We look at the various disease equilibrium points and investigate the regional stability of the disease-free and endemic equilibrium points in the feasible region of the epidemic model. Concurrently, the global stability of the equilibrium points is investigated using the Lyapunov functional approach. Finally, the Runge-Kutta method is utilised for numerical simulation, and graphic illustrations are used to evaluate the impact of different factors on the spread of the illness. Critical factors that effect the dynamics of disease transmission and greatly affect the rate and range of the disease's spread in the population have been determined through a thorough analysis. These factors are crucial in determining the expansion of the disease.

In vivo effects of a selected thiourea derivative 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) against nociception, inflammation and gastric ulcerogenicity: Biochemical, histopathological and in silico approaches.

The current study was designed to investigate the potential of a synthetic therapeutic agent for better management of pain and inflammation, exhibiting minimal to non-existent ulcerogenic effects. The effect of 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea was assessed through model systems of nociception and anti-inflammatory activities in mice. In addition, the ulcerogenic potential was evaluated in rats using the NSAID-induced pyloric ligation model, followed by histopathological and biochemical analysis. The test was conducted on eight groups of albino rats, comprising of group I (normal saline), groups II and III (aspirin® at doses of 100 mg/kg and 150 mg/kg, respectively), groups IV and V (indomethacin at doses of 100 mg/kg and 150 mg/kg, respectively), and groups VI, VII, and VIII (lead-compound at 15 mg/kg, 30 mg/kg and 45 mg/kg doses, respectively). Furthermore, molecular docking analyses were performed to predict potential molecular target site interactions. The results showed that the lead-compound, administered at doses of 15, 30, and 45 mg/kg, yielded significant reductions in chemically and thermally induced nociceptive pain, aligning with the levels observed for aspirin® and tramadol. The compound also effectively suppressed inflammatory response in the carrageenan-induced paw edema model. As for the ulcerogenic effects, the compound groups displayed no considerable alterations compared to the aspirin® and indomethacin groups, which displayed substantial increases in ulcer scores, total acidity, free acidity, and gastric juice volume, and a decrease in gastric juice pH. In conclusion, these findings suggest that our test compound exhibits potent antinociceptive, anti-inflammatory properties and is devoid of ulcerogenic effects.

Demographic and clinical features of dengue fever infection in Pakistan: a cross-sectional epidemiological study.

BACKGROUND: Dengue fever caused by dengue virus is a tropical disease and is among the deadliest vector-borne diseases. The humid and hot summers of Pakistan support the probation of the vectors responsible for the transmission of viral and other parasitic diseases. METHODOLOGY: A retrospective study, from 2012- 2019, of dengue infected individuals from the Punjab province of Pakistan was carried out to analyze epidemiology, clinical and laboratory findings of subjects with dengue virus infection. Data was derived from National Institute of Health (NIH) followed by Dengue control program of Pakistan, covering the incidence rate in 36 districts of Punjab and Islamabad Capital Territory (ICT) respectively. Patients data including the presence of dengue specific antigen or/and antibodies such as NS1 and IgG/IgM were observed. The study also included the analysis of demographic data, geographic data, and the month-wise distribution of dengue cases to examine seasonal trends. RESULTS: We analyzed 25,682 dengue infected individuals. The statistical analysis revealed a significant association between genders in which male population was more affected by dengue than females. It was also noted that the middle age group was the most affected age group while the highest number of cases were reported in October. Rawalpindi and Lahore were the most affected cities in Punjab province while Islamabad represented the highest number of cases during the recent outbreak in 2019. The IgM and IgG antibodies were highly prevalent among the infected patients. CONCLUSION: Dengue is endemic in Pakistan, circulating throughout the year. Highest number of cases were observed in the month of October, September and November respectively. Association between climate change and vector-borne diseases need to be investigated in Pakistan as they significantly influence the timing and intensity of dengue and other disease outbreaks. Further exploration of hematological parameters is required to better diagnose and treat the disease. For the effective control of dengue outbreaks, awareness campaigns on sewage management and vector control along with social factors are strongly recommended for better control and eradication of the disease.

Polyphenols and their nanoformulations as potential antibiofilm agents against multidrug-resistant pathogens.

The emergence of multidrug-resistant (MDR) pathogens is a major problem in the therapeutic management of infectious diseases. Among the bacterial resistance mechanisms is the development of an enveloped protein and polysaccharide-hydrated matrix called a biofilm. Polyphenolics have demonstrated beneficial antibacterial effects. Phenolic compounds mediate their antibiofilm effects via disruption of the bacterial membrane, deprivation of substrate, protein binding, binding to adhesion complex, viral fusion blockage and interactions with eukaryotic DNA. However, these compounds have limitations of chemical instability, low bioavailability, poor water solubility and short half-lives. Nanoformulations offer a promising solution to overcome these challenges by enhancing their antibacterial potential. This review summarizes the antibiofilm role of polyphenolics, their underlying mechanisms and their potential role as resistance-modifying agents.

Bacteria can become more difficult to kill by forming a protective layer called a biofilm. This is a problem because infections caused by these bacteria can be difficult to treat. Polyphenols are a natural compound found in plants. They have shown promise in fighting resistant bacteria by stopping bacteria from forming a biofilm. However, polyphenols have some limitations. These limitations can be overcome by using nanomaterials, which are types of tiny particles. When polyphenols are combined with nanomaterials, they become much better at fighting bacteria. This is a promising solution to treating resistant infections caused by biofilm-forming bacteria.

Impact of climate change on potential distribution of Dickeya zeae causal agent of stalk rot of maize in Sialkot district Pakistan.

Maize (Zea mays) is an influential crop in its production across the world. However, the invasion of many phytopathogens greatly affects the maize crop yield at various hotspot areas. Of many diseases, bacterial stalk rot of maize caused by Dickeya zeae results in severe yield reduction, thus the need for efficient management is important. Further, to produce epidemiological information for control of disease outbreaks in the hot spot regions of Sialkot District, Punjab Pakistan, extensive field surveys during 2021 showed that out of 266 visited areas, the highest disease incidence ranging from 66.5 to 78.5% while the lowest incidence was ranging from 9 to 20%. The Maxent modeling revealed that among 19 environmental variables, four variables including temperature seasonality (bio-4), mean temperature of the wettest quarter (bio-8), annual precipitation (bio-12), and precipitation of driest month (bio-14) were significantly contributing to disease distribution in current and coming years. The study outcomes revealed that disease spread will likely increase across four tehsils of Sialkot over the years 2050 and 2070. Our findings will be helpful to policymakers and researchers in devising effective disease management strategies against bacterial stalk rot of maize outbreaks in Sialkot, Pakistan.

Phytochemical analysis, radical scavenging and glioblastoma U87 cells toxicity studies of stem bark of buckthorn (Rhamnus pentapomica R. Parker).

BACKGROUND: During the past two decades, the correlation between oxidative stress and a variety of serious illnesses such as atherosclerosis, chronic obstructive pulmonary disease (COPD), Alzheimer disease (AD) and cancer has been established. Medicinal plants and their derived phytochemicals have proven efficacy against free radicals and their associated diseases. The current work was aimed to evaluate the phytochemical constituents of Rhamnus pentapomica R. Parker via Gas Chromatography-Mass Spectrometry (GC-MS) and its antioxidant and anti-glioblastoma potentials. METHODS: The bioactive compounds were analysed in Rhamnus pentapomica R. Parker stem bark extracts by GC-MS analysis, and to evaluate their antioxidant and anti-glioblastoma effects following standard procedures. The stem bark was extracted with 80% methanol for 14 days to get crude methanolic extract (Rp.Cme) followed by polarity directed fractionation using solvents including ethyl acetate, chloroform, butanol to get ethyl acetate fraction (Rp.EtAc), chloroform fraction (Rp.Chf) and butanol fraction (Rp.Bt) respectively. Antioxidant assay was performed using DPPH free radicals and cell viability assay against U87 glioblastoma cancer cell lines was performed via MTT assay. RESULTS: In GC-MS analysis, thirty-one compounds were detected in Rp.Cme, 22 in Rp.Chf, 24 in Rp.EtAc and 18 compounds were detected in Rp.Bt. Among the identified compounds in Rp.Cme, 9-Octadecenoic acid (Z)-methyl ester (7.73%), Octasiloxane (5.13%) and Heptasiloxane (5.13%), Hexadecanoic acid, methyl ester (3.76%) and Pentadecanoic acid, 14-methyl-, methyl Ester (3.76%) were highly abundant.. In Rp.Chf, Benzene, 1,3-dimethyl- (3.24%) and in Rp.EtAc Benzene, 1,3-dimethyl-(11.29%) were highly abundant compounds. Antioxidant studies revealed that Rp.Cme and Rp.EtAc exhibit considerable antioxidant potentials with IC50 values of 153.53 µg/ml and 169.62 µg/ml respectively. Both fractions were also highly effective against glioblastoma cells with IC50 of 147.64 µg/ml and 76.41ug/ml respectively. CONCLUSION: Phytochemical analysis revealed the presence of important metabolites which might be active against free radicals and glioblastoma cells. Various samples of the plant exhibited considerable antioxidant and anti-glioblastoma potentials warranting further detailed studies.

Neuroprotective potentials of Lead phytochemicals against Alzheimer's disease with focus on oxidative stress-mediated signaling pathways: Pharmacokinetic challenges, target specificity, clinical trials and future perspectives.

BACKGROUND: Alzheimer's diseases (AD) and dementia are among the highly prevalent neurological disorders characterized by deposition of beta amyloid (Aß) plaques, dense deposits of highly phosphorylated tau proteins, insufficiency of acetylcholine (ACh) and imbalance in glutamatergic system. Patients typically experience cognitive, behavioral alterations and are unable to perform their routine activities. Evidence also suggests that inflammatory processes including excessive microglia activation, high expression of inflammatory cytokines and release of free radicals. Thus, targeting inflammatory pathways beside other targets might be the key factors to control- disease symptoms and progression. PURPOSE: This review is aimed to highlight the mechanisms and pathways involved in the neuroprotective potentials of lead phytochemicals. Further to provide updates regarding challenges associated with their use and their progress into clinical trials as potential lead compounds. METHODS: Most recent scientific literature on pre-clinical and clinical data published in quality journals especially on the lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin was collected using SciFinder, PubMed, Google Scholar, Web of Science, JSTOR, EBSCO, Scopus and other related web sources. RESULTS: Literature review indicated that the drug discovery against AD is insufficient and only few drugs are clinically approved which have limited efficacy. Among the therapeutic options, natural products have got tremendous attraction owing to their molecular diversity, their safety and efficacy. Research suggest that natural products can delay the disease onset, reduce its progression and regenerate the damage via their anti-amyloid, anti-inflammatory and antioxidant potentials. These agents regulate the pathways involved in the release of neurotrophins which are implicated in neuronal survival and function. Highly potential lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin regulate neuroprotective signaling pathways implicated in neurotrophins-mediated activation of tropomyosin receptor kinase (Trk) and p75 neurotrophins receptor (p75NTR) family receptors. CONCLUSIONS: Phytochemicals especially phenolic compounds were identified as highly potential molecules which ameliorate oxidative stress induced neurodegeneration, reduce Aß load and inhibit vital enzymes. Yet their clinical efficacy and bioavailability are the major challenges which need further interventions for more effective therapeutic outcomes.

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.

Waterborne pathogens detection technologies: advances, challenges, and future perspectives.

The World Health Organization (WHO) estimated that pathogens like Escherichia coli, primarily linked to food and water contamination, are associated with 485,000 deaths from diarrheal diseases annually, translating to a staggering worldwide economic loss of nearly 12 billion USD per annum. International organizations like the WHO and United Nations Children's Fund (UNICEF) have established related guidelines and criteria for pathogenic detection technologies and driving the search for innovative and efficient detection methods. This comprehensive review examines the trajectory of waterborne pathogenic bacteria detection technologies from traditional techniques, i.e., culture-based methods, to current detection methods including various forms of polymerase chain reaction (PCR) techniques [qualitative real-time PCR, digital PCR, ELISA, loop-mediated isothermal amplification, next-generation sequencing (NGS)] and to emerging techniques, i.e., biosensors and artificial intelligence (AI). The scope of the review paper focuses on waterborne pathogenic bacteria that are recognized as human pathogens, posing tangible threats to public health through waterborne. The detection techniques' merits, constraints, research gaps and future perspectives are critically discussed. Advancements in digital droplet PCR, NGS and biosensors have significantly improved sensitivity and specificity, revolutionizing pathogen detection. Additionally, the integration of artificial intelligence (AI) with these technologies has enhanced detection accuracy, enabling real-time analysis of large datasets. Molecular-based methods and biosensors show promise for efficient water quality monitoring, especially in resource-constrained settings, but on-site practical implementation remains a challenge. The pairwise comparison metrics used in this review also offer valuable insights into quick evaluation on the advantages, limitations and research gaps of various techniques, focusing on their applicability in field settings and timely analyses. Future research efforts should focus on developing robust, cost-effective and user-friendly techniques for routine waterborne bacteria monitoring, ultimately safeguarding global water supplies and public health, with AI and data analysis playing a crucial role in advancing these methods for a safer environment.

Polyhydroquinoline derivatives for diabetic management: synthesis, in vitro and in silico approaches.

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23 ± 0.03 to 73.85 ± 0.61 µM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.

Broad-spectrum antagonistic potential of Bacillus spp. volatiles against Rhizoctonia solani and Xanthomonas oryzae pv. oryzae.

Rhizoctonia solani and Xanthomonas oryzae pv. oryzae (Xoo) are the two major diseases affecting the quality and quantity of rice production. In the current study, volatile organic compounds (VOCs) of Bacillus spp. were used as green biocontrol agents for plant diseases. In in vitro experiments, Bacillus spp. FZB42, NMTD17, and LLTC93-VOCs displayed strong antimicrobial volatile activity with inhibition rates of 76, 66, and 78% for R. solani and 78, 81, and 76% for Xoo, respectively, compared to control. The synthetic VOCs, namely Pentadecane (PDC), Benzaldehyde (BDH), 1,2-Benz isothiazol-3(2H)-one (1,2-BIT), and mixture (MIX) of VOCs showed high volatile activity with inhibition rates of 86, 86, 89, and 92% against R. solani and 81, 81, 82, and 86%, respectively, against Xoo as compared to control. In addition, the scanning and transmission electron microscopes (SEM and TEM) analyses were performed to examine the effect of Bacillus and synthetic VOC treatments on R. solani and Xoo morphology. The analysis revealed the deformed and irregularized morphology of R. solani mycelia and Xoo cells after VOC treatments. The microscopic analysis showed that the rapid inhibition was due to severe oxidative productions inside the R. solani mycelia and Xoo cells. By using molecular docking, it was determined that the synthetic VOCs entered the active binding site of trehalase and NADH dehydrogenase proteins, causing R. solani and Xoo cells to die prematurely and an accumulation of ROS. In the greenhouse experiment, FZB42, NMTD17, and LLTC93-VOCs significantly reduced the lesions of R. solani 8, 7, and 6 cm, and Xoo 7, 6, and 6 cm, respectively, then control. The synthetic VOCs demonstrated that the PDC, BDH, 1,2-BIT, and MIX-VOCs significantly reduced R. solani lesions on leaves 6, 6, 6, and 5 cm and Xoo 6, 5, 5, and 4 cm, respectively, as compared to control. Furthermore, plant defence-related genes and antioxidant enzymes were upregulated in rice plants. These findings provide novel mechanisms by which Bacillus antimicrobial VOCs control plant diseases.

Neuroprotective evaluation of diospyrin against drug-induced Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC50 values of 95 µg/mL for AChE and 110 µg/mL for BChE as compared to the standard drug donepezil (IC50: 95 & 85 µg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC50: 139.74 µg/mL) of DPPH-free radicals at the highest concentration of 1000 µg/mL as compared to the ascorbic acid (IC50: 13.72 µg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.

Antibiotics resistance as a major public health concern: A pharmaco-epidemiological study to evaluate prevalence and antibiotics susceptibility-resistance pattern of bacterial isolates from multiple teaching hospitals.

BACKGROUND: Multi Drugs Resistance (MDR) is among the most worrisome healthcare issues resulting from inappropriate and indiscriminate utilization of antimicrobial agents which has compromised the efficacy and reliability of antimicrobial agents (AMAs). This has not only put a huge burden on the health care system but also is a major cause of morbidity and mortality. This project was designed to evaluate the prevalence of various microbial strains among patients admitted to various teaching hospitals and to assess their susceptibility and resistance towards clinically approved antibiotics. METHODS: The study was conducted during August 2021-February 2022 to determine the prevalence of common resistant strains of bacteria and to analyze their susceptibility pattern to the commonly prescribed antibiotics using standard procedures. One hundred and thirty biological samples including urine, blood, cerebrospinal fluid (CSF), wound swabs, pus and sputum were collected from the site of infection from the patients admitted at different wards of North West General Hospital (NWGH), Peshawar, Pakistan, Khyber Teaching Hospital (KTH), Peshawar Pakistan, and Hayat Abad Medical Complex (HMC) Peshawar Pakistan. Samples were collected and cultured following standard hospital procedures. The cultured samples were subjected to identification procedures including Gram staining, morphological characterization of bacterial colonies and biochemical assessments. The identified bacteria were tested for their susceptibility using Kirby-Bauer disc diffusion method. The diameter of Inhibitory Zones (DIZ) was analyzed following Clinical and Laboratory Standards Institute (CLSI) criteria. Minimum Inhibitory Concentrations (MICs) were evaluated using agar dilution method. Antimicrobials sensitivity were presented as antibiogram following CLSI M39 standard. RESULTS: A total of one hundred and thirty biological samples were collected, out of which one hundred and nine samples were positive for bacterial growth and were further processed for detailed analysis. The frequency and type of bacteria isolated from various cultures indicated that Gram negative bacteria (n = 92/109) were more dominant than Gram-positive (n = 17/109) pathogens. The most prevalent bacteria isolated was Escherichia coli (29.35 %), followed by Staphylococcus aureus (15.59 %), and Klebsiella spp, (12.84 %). In addition, other pathogens including, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. showed a prevalence of 9.175 %, 8.25 %, and 5.50 % respectively. As indicated in the antbiogram, several organisms exhibited considerble decline in the sensitivies towards various antibiotics. A high percentage of resistance was observed against some antibiotics including trimethoprim, co-trimoxazole, amoxicillin/clavulanate, ciprofloxacin, piperacillin/tazobactam, cefotaxime and ceftazidime. CONCLUSION: The prevalence of resistant strains of pathogens is increasing day by day, while the antibiotics commonly prescribed against them are losing their efficacy, which is pushing the world to the era of pre-antibiotics. Unfortunately, the discovery of novel antibiotics is limited and researchers speculate that the is pushing towards pre-antibiotics era. Subsequently, efforts must be directed towards ensuring rational antibiotics use to prevent emergence of MDR pathogens. Our findings indicated that Gram negative bacteria including Escherichia coli was most prevalent. Other bacterial strains including S. aureus, Klebsiella spp, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. were found among the causative agents. Unfortunately, considerable decline in the sensitivities of various bacterial isolated were observed towards the tested antibiotics. Previous studies reported the high prevalence of E. coli and S. aureus in clinical samples of Pakistani hospitals including hospitals in Peshawar and thus our findings are in agreement with the previous reports. Pharmacists being experts can play their role by promoting the optimal use of antimicrobial agents and educating healthcare professionals, patients and the public.

Phytochemicals-based ß-amyloid cleaving enzyme-1 and MAO-B inhibitors for the treatment of Alzheimer's disease: molecular simulations-based predictions.

Alzheimer's disease (AD) is among the highly prevalent neurodegenerative disorder of the aging brain and is allied with cognitive and behavioral abnormalities. Unfortunately, there is very limited drug discovery for the effective management of AD, and the clinically approved drugs have limited efficacy. Consequently, there is an immediate demand for the development of new compounds that have the ability to act as multitarget-directed ligands (MTDLs). As major pathological targets of the disease, the current study aimed to investigate lead natural bioactive compounds including apigenin, epigallocatechin-3-gallate, berberine, curcumin, genistein, luteolin, quercetin, resveratrol for their inhibitory potentials against ß-amyloid cleaving enzyme-1 (BACE1) and monoamine oxidase-B (MAO-B) enzymes. The study compounds were docked against the target enzymes (MAO-B and BACE1) using MOE software and subsequent molecular dynamics simulations (MDS) studies. The molecular docking analysis revealed that these phytochemicals (MTDLs) showed good interactions with the target enzymes as compared to the reference inhibitors. Among these eight phytocompounds, the epigallocatechin-3-gallate compound was an active inhibitor against both drug targets, with the highest docking scores and good interactions with the active residues of the enzymes. Furthermore, the docking result of the active one inhibitor in complex with the target enzymes (epigallocatechin-3-gallate/BACE1, epigallocatechin-3-gallate/MAO-B, reference/BACE1 and reference/MAO-B) were further validated by MDS. According to the findings of our study, epigallocatechin-3-gallate has the potential to be a candidate for use in the treatment of neurological illnesses like AD. This compound has MTDL potential and may be exploited to create new compounds with disease-modifying features.Communicated by Ramaswamy H. Sarma.

Phyto-fabrication of ultrafine nanoscale holmium oxide HT-Ho2O3 NPs and their biomedical potential.

In this study holmium oxide nanoparticles (Ho2O3 NPs) are fabricated using Hyphaene thebaica extracts as a bioreductant. The XRD pattern of HT-Ho2O3 NPs (product from phyto-reduction) suggested that the nanoparticles are crystalline with no impurities. Scherrer approximation revealed grain sizes of ∼10 nm. The HR-TEM revealed HT-Ho2O3 NPs possessed a quasi-spherical morphology complemented by SEM and the particle sizes were in the range of 6-12 nm. The infrared spectra revealed characteristic Ho-O bonding at ∼603 cm-1. Raman spectra indicated five main peaks positioned at 156 cm-1, 214 cm-1, 328 cm-1, 379 cm-1 and 607 cm-1. Eg (optical bandgap) was found to be 5.1 eV. PL spectra indicated two major peaks at 415 nm and 607 nm. EDS spectra confirmed the elemental presence of holmium (Ho). Spotty rings were obtained during the SAED measurement which indicated crystallinity of HT-Ho2O3 NPs. The HT-Ho2O3 NPs were further analyzed for their antioxidant, anti-angiogenic and cytotoxic properties. The antioxidant potential was moderate i.e., 43.40 ± 0.96% at 1000 µg mL-1 which decreased in a dose dependent manner. Brine shrimp lethality was highest at 1000 µg mL-1 with the LC50 320.4 µg mL-1. Moderate anti-angiogenic potential was observed using in ova CAM assay. MTT bioassay revealed that the HT-Ho2O3 NPs inhibited the 3T3 cells (IC50 67.9 µg mL-1), however, no significant inhibition was observed against MCF-7 cells. α-Amylase and ß-glucosidase inhibition revealed that the HT-Ho2O3 NPs can be of use in controlling blood glucose levels. Overall, it can be concluded that biosynthesis using aqueous extracts can be a suitable alternative in finding ecofriendly paradigms for the synthesis of nanoparticles. We suggest extended research into the bioreduced Ho2O3 NPs for establishing their biomedical potential and toxicity.

Discovery of (S)-flurbiprofen-based novel azine derivatives as prostaglandin endoperoxide synthase-II inhibitors: Synthesis, in-vivo analgesic, anti-inflammatory activities, and their molecular docking.

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.

Nanomedicine as a potential novel therapeutic approach against the dengue virus.

Dengue is an arbovirus infection which is transmitted by Aedes mosquitoes. Its prompt detection and effective treatment is a global health challenge. Various nanoparticle-based vaccines have been formulated to present immunogen (antigens) to instigate an immune response or prevent virus spread, but no specific treatment has been devised. This review explores the role of nanomedicine-based therapeutic agents against dengue virus, taking into consideration the applicable dengue virus assays that are sensitive, specific, have a short turnaround time and are inexpensive. Various kinds of metallic, polymeric and lipid nanoparticles with safe and effective profiles present an alternative strategy that could provide a better remedy for eradicating the dengue virus.

Bacterial and Fungal Biocontrol Agents for Plant Disease Protection: Journey from Lab to Field, Current Status, Challenges, and Global Perspectives.

Plants are constantly exposed to various phytopathogens such as fungi, Oomycetes, nematodes, bacteria, and viruses. These pathogens can significantly reduce the productivity of important crops worldwide, with annual crop yield losses ranging from 20% to 40% caused by various pathogenic diseases. While the use of chemical pesticides has been effective at controlling multiple diseases in major crops, excessive use of synthetic chemicals has detrimental effects on the environment and human health, which discourages pesticide application in the agriculture sector. As a result, researchers worldwide have shifted their focus towards alternative eco-friendly strategies to prevent plant diseases. Biocontrol of phytopathogens is a less toxic and safer method that reduces the severity of various crop diseases. A variety of biological control agents (BCAs) are available for use, but further research is needed to identify potential microbes and their natural products with a broad-spectrum antagonistic activity to control crop diseases. This review aims to highlight the importance of biocontrol strategies for managing crop diseases. Furthermore, the role of beneficial microbes in controlling plant diseases and the current status of their biocontrol mechanisms will be summarized. The review will also cover the challenges and the need for the future development of biocontrol methods to ensure efficient crop disease management for sustainable agriculture.

Impact of variable thermal conductivity on flow of trihybrid nanofluid over a stretching surface.

The present article describes the impact of variable thermal conductivity on the flow of ternary hybrid nanofluid with cylindrical shape nanoparticles over a stretching surface. Three nanoparticles combine in base fluid polymer. The assumption made will be used to model an equations. Modeled equations are in the form of a system of partial differential equations are difficult to solve can be converted to system of an ordinary differential equations, through resemblance substitutions, and will be solved numerically. Numerical scheme of Runge-Kutta order four is coupled with the shooting method to solve the resulting equations. The graphs in the study illustrate how physical quantities, such as magnetic field, injection/suction, nanoparticles volume fraction, and variable thermal conductivity, affected the velocity, skin friction, temperature, and local Nusselt number. The velocity profiles deflate as the volume fraction rises. While the temperature rises with an increase in the volume fraction of nanoparticles for both injection and suction, the velocity profiles also decline as the injection and suction parameter increases. Furthermore, as the magnetic field increases, the temperature profile rises while the velocity profile falls. The temperature curves increase as thermal conductivity increases. Finally, as the magnetic field is strengthened, the Nusselt number and skin friction decrease. The combination of mathematical modeling, numerical solution techniques, and the analysis of physical quantities contributes to the advancement of knowledge in this ternary hybrid nanofluid.