Crafting a powerful shield: Unveiling the potent anti-oxidant magic of ex-situ nanostructured Ag/WO3 composite.

The current study focuses the nanocomposites of Ag/WO3 was synthesized via hydrothermal method and extract of Aloe-vera gel was used. Various characterization techniques were used for the analysis of Ag/WO3 nanocomposites which includes SEM (scanning electron microscope), EDX (Energy dispersive spectroscopy), XRD (X-ray diffraction), FTIR (Fourier transform infrared), UV (ultraviolet-visible-spectroscopy) to tell about elemental composition, shape and crystalline structure, band gap, functional group. The presence of composition of elements O, W, Ag in Ag/WO3 nanocomposites was confirmed through EDX spectrum. The hexagonal crystal structure and the border peaks in Ag/WO3 nanocomposites were examined through XRD spectra. The Anti-oxidant activity was synthesized by using (DPPH) free Radical in Ag/WO3 nanocomposites. The outcomes of present study exhibited an excellent anti-oxidant activity and also indicated the reduction of stabilized free radical DPPH analysis using Aloe vera extract. The result revealed that the anti-oxidant activity of Ag/WO3 nanocomposites is essential for biomedical application and various industries.

Effect of Mn Doped on Structural, Optical, and Dielectric Properties of BiFe1-xMnxO3 for Efficient Antioxidant Activity.

Manganese-doped bismuth ferrites were synthesized using the coprecipitation method with the green extract Azadirachta indica. Our incorporation of the transition element, manganese, into bismuth ferrites tackles the challenge of increased leakage current often observed in intrinsic bismuth ferrites. We gained key insights through a comprehensive examination of the structural, dielectric, and optical properties of these materials, utilizing Fourier transform infrared spectroscopy (FTIR), impedance spectroscopy, and UV-visible spectroscopy, respectively. The formation of an octahedral geometry was confirmed using the FTIR technique. UV-visible spectroscopy indicated that 2% Mn doping is optimal, while we obtained a low band gap energy (2.21 eV) and high refractive index (3.010) at this amount of doping. The manufactured materials exhibited the typical ferrite-like dielectric response, that is, the dielectric parameter gradually decreased as the frequency increased and then stayed constant in the high-frequency range. Using the diphenylpicrylhydrazyl (DPPH) free radical assay, we also examined the antioxidant activity of bismuth ferrites. We concluded that among different Mn-doped BiFeMnO3-based nanomaterials, the 2 wt % Mn-doped BiFeMnO3 shows the highest antioxidant activity. This finding substantiates the efficacy of the optimized material with regard to its potent antioxidant activity, positioning it as a promising candidate for potential biomedical applications.

Bioinformatics and systems biology analysis revealed PMID26394986-Compound-10 as potential repurposable drug against covid-19.

The global health pandemic known as COVID-19, which stems from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a significant concern worldwide. Several treatment methods exist for COVID-19; however, there is an urgent demand for previously established drugs and vaccines to effectively combat the disease. Since, discovering new drugs poses a significant challenge, making the repurposing of existing drugs can potentially reduce time and costs compared to developing entirely new drugs from scratch. The objective of this study is to identify hub genes and associated repurposed drugs targeting them. We analyzed differentially expressed genes (DEGs) by analyzing RNA-seq transcriptomic datasets and integrated with genes associated with COVID-19 present in different databases. We detected 173 Covid-19 associated genes for the construction of a protein-protein interaction (PPI) network which resulted in the identification of the top 10 hub genes/proteins (STAT1, IRF7, MX1, IRF9, ISG15, OAS3, OAS2, OAS1, IRF3, and IRF1). Hub genes were subjected to GO functional and KEGG pathway enrichment analyses, which indicated some key roles and signaling pathways that were strongly related to SARS-CoV-2 infections. We conducted drug repurposing analysis using CMap, TTD, and DrugBank databases with these 10 hub genes, leading to the identification of Piceatannol, CKD-712, and PMID26394986-Compound-10 as top-ranked candidate drugs. Finally, drug-gene interactions analysis through molecular docking and validated via molecular dynamic simulation for 80 ns suggests PMID26394986-Compound-10 as the only potential drug. Our research demonstrates how in silico analysis might produce repurposing candidates to help respond faster to new disease outbreaks.Communicated by Ramaswamy H. Sarma.

Sustainable, economical and rapid treatment of multiple lung diseases using therapeutic potential of curcumin nanoparticles.

The study was designed to prepare pure curcumin nanoparticles in rapid and simple way for target specific drug delivery to kill bacteria lying deep down within the alveoli of lungs via inhaler. Three different methods including evaporation precipitation of nanosuspension (ENP), solid dispersion (SD) and anti-solvent precipitation (ASP) were selected to prepare nanocurcumin in pure form in very simple way. This was done to compare their efficiency in terms of particle size obtained and water solubility and bacterial toxicity of as prepared curcumin nanoparticles. In this comparative study, curcumin NPs obtained from three different methods having particles size 65.3 nm, 98.7 nm and 47.4 nm respectively. The NPs were characterized using various techniques like SEM, XRD, UV-Visible and FTIR for their particle size determination and solubility evaluation. These particles were screened off against five bacterial strains causing lung diseases. AB3 prepared by ASP method, being smallest sized nanostructures, showed maximum solubility in water. These nanoparticles can be used as drug directly via inhaler to the target area without using any support or nano-carrier. In this way minimum dose formulation is required to target bacteria.

Antibiotic Drug Resistance Pattern of Uropathogens in Pediatric Patients in Pakistani Population.

The common prevalent diseases in the age of 0 to 6 are related to urinary tract infections. If not properly diagnosed, they will lead to urological and nephrological complications. Uropathogens are developing resistance against most drugs and are harder to treat. A study was done on the inpatients and outpatients of the two hospitals located in Lahore. A total of 39,750 samples that were both male and female were collected. Escherichia and Klebsiella were found in 234 samples based on biochemical characterization, growth on CLED agar, and white blood cell/pus cell (WBC) microscopy. In comparison to males, female samples had a higher number of uropathogens (1:1.29). From the samples of Shaikh Zayed Hospital (SZH), the ratio of Klebsiella to Escherichia (1:1.93) was reported, while this ratio was 1.84:1 from the Children Hospital (CH). The incidence of UTI was higher in the month of September. Randomly selected Escherichia and Klebsiella were verified via a 16S rRNA sequence. Antibiotic resistance profiling of isolated bacterial strains was done against 23 antibiotics. The most efficient antibiotics against Klebsiella and Escherichia were colistin sulphate (100% sensitivity against bacteria from CH; 99.3% against strains from SZH) and polymyxin B (100% sensitivity against strains from SZH; 98.8% against strains from CH). Sensitivity of the total tested strains against meropenem (74%, SZH; 70% CH), Fosfomycin (68%, SZH; 73% CH strains), amikacin (74% SZH; 55% CH), and nitrofurantoin (71% SZH;67% CH) was found, Amoxicillin, ampicillin, and cefuroxime showed 100 to ≥90% resistance and are the least effective.

Comparative molecular docking analysis for analyzing the inhibitory effect of Anakinra and Ustekinumab against IL17F.

Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger's Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex.Communicated by Ramaswamy H. Sarma.

Ex Situ Synthesis and Characterizations of MoS2/WO3 Heterostructures for Efficient Photocatalytic Degradation of RhB.

In this study, novel hydrothermal ex situ synthesis was adopted to synthesize MoS2/WO3 heterostructures using two different molar ratios of 1:1 and 1:4. The "bottom-up" assembly was successfully developed to synthesize spherical and flaky-shaped heterostructures. Their structural, morphological, compositional, and bandgap characterizations were investigated through XRD, EDX, SEM, UV-Visible spectroscopy, and FTIR analysis. These analyses help to understand the agglomerated heterostructures of MoS2/WO3 for their possible photocatalytic application. Therefore, prepared heterostructures were tested for RhB photodegradation using solar light irradiation. The % efficiency of MoS2/WO3 composites for 30 min irradiation of 1:1 was 91.41% and for 1:4 was 98.16%. Similarly, the % efficiency of 1:1 MoS2/WO3 heterostructures for 60 min exposure was 92.68%; for 1:4, it was observed as 98.56%; and for 90 min exposure, the % efficiency of 1:1 was 92.41%, and 98.48% was calculated for 1:4 composites. The photocatalytic efficiency was further verified by reusability experiments (three cycles), and the characterization results afterward indicated the ensemble of crystalline planes that were responsible for the high efficiency. Moreover, these heterostructures showed stability over three cycles, indicating their future applications for other photocatalytic applications.

In Vivo Assessment of the Ameliorative Impact of Some Medicinal Plant Extracts on Lipopolysaccharide-Induced Multiple Sclerosis in Wistar Rats.

Multiple sclerosis is a chronic autoimmune disorder that leads to the demyelination of nerve fibers, which is the major cause of non-traumatic disability all around the world. Herbal plants Nepeta hindustana L., Vitex negundo L., and Argemone albiflora L., in addition to anti-inflammatory and anti-oxidative effects, have shown great potential as neuroprotective agents. The study was aimed to develop a neuroprotective model to study the effectiveness of herbal plants (N. hindustana, V. negundo, and A. albiflora) against multiple sclerosis. The in vivo neuroprotective effects of ethanolic extracts isolated from N. hindustana, V. negundo, and A. albiflora were evaluated in lipopolysaccharides (LPS) induced multiple sclerosis Wistar rat model. The rat models were categorized into seven groups including group A as normal, B as LPS induced diseased group, while C, D, E, F, and G were designed as treatment groups. Histopathological evaluation and biochemical markers including stress and inflammatory (MMP-6, MDA, TNF-α, AOPPs, AGEs, NO, IL-17 and IL-2), antioxidant (SOD, GSH, CAT, GPx), DNA damage (Isop-2α, 8OHdG) as well as molecular biomarkers (RAGE, Caspase-8, p38) along with glutamate, homocysteine, acetylcholinesterase, and myelin binding protein (MBP) were investigated. The obtained data were analyzed using SPSS version 21 and GraphPad Prism 8.0. The different extract treated groups (C, D, E, F, G) displayed a substantial neuroprotective effect regarding remyelination of axonal terminals and oligodendrocytes migration, reduced lymphocytic infiltrations, and reduced necrosis of Purkinje cells. The levels of stress, inflammatory, and DNA damage markers were observed high in the diseased group B, which were reduced after treatments with plant extracts. The antioxidant activity was significantly reduced in diseased induced group B, however, their levels were raised after treatment with plant extract. Group F (a mélange of all the extracts) showed the most significant change among all other treatment groups (C, D, E, G). The communal dose of selected plant extracts regulates neurodegeneration at the cellular level resulting in restoration and remyelination of axonal neurons. Moreover, 400 mg/kg dose of three plants in conjugation (Group F) were found to be more effective in restoring the normal activities of all measured parameters than independent doses (Group C, D, E) and is comparable with standard drug nimodipine (Group G) clinically used for the treatment of multiple sclerosis. The present study, for the first time, reported the clinical evidence of N. hindustana, V. negundo, and A. albiflora against multiple sclerosis and concludes that all three plants showed remyelination as well neuroprotective effects which may be used as a potential natural neurotherapeutic agent against multiple sclerosis.

Hybridization of tumor homing and mitochondria-targeting peptide domains to design novel dual-imaging self-assembled peptide nanoparticles for theranostic applications.

A novel hybridized dual-targeting peptide-based nanoprobe was successfully designed by using the cyclic heptapeptide. This peptide has Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence, in which the RGD homing motif and KALK mitochondria-targeting motif were linked via amide bond. The designed peptide probe was further modified through covalent linkage to induce dual-imaging functionality, and self-assembled to form spherical nanoparticles. The novel Cy5.5-SAPD-99mTc nanoparticles were tested for in vitro cytotoxicity, cellular uptake, and apoptosis-inducing functionalities. The cellular internalization, enhanced cytotoxicity and selective receptor binding capabilities against U87MG cells, excellent dual-imaging potential, improved apoptosis-inducing feature by damaging mitochondria, and in vivo preclinical investigations suggested that our newly designed novel hybridized peptide-based dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme. This study describes the development of dual-targeting self-assembled peptide nanoparticles followed by modifications using NIRF dye and radiolabeled with 99mTc for dual-imaging and enhanced therapeutic efficacy against brain tumor.

Circulating miR-146a expression as a non-invasive predictive biomarker for acute lymphoblastic leukemia.

Dysregulation of non-coding microRNAs during the course of tumor development, invasion and/or progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies. This exploratory study aims at evaluating the usefulness of plasma concentration of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL). Total RNA including miRNA was isolated from 110 plasma samples of patients (n = 66), healthy controls (n = 24) and follow up (n = 20) cases and reverse transcribed. Relative concentrations were assessed using real-time quantitative PCR and fold-change was calculated by 2-ΔΔCt method. Finally, relative concentrations were correlated to clinicopathological factors. Patients (n = 66) were analyzed to determine fold expression of miR-146a in plasma samples of ALL. Before chemotherapy, pediatric (n = 42) and adult (n = 24) showed overexpression of miR-146a compared with healthy controls (P < 0.0001). There was no effect of age and gender on mir-146a expression in plasma. mirR-146a expression was independent of clinical and hematological features. Moreover, miR-146a levels in plasma of paired samples (n = 20) after treatment showed significant decrease in expression (P < 0.001). Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with ALL. Moreover predicted targets may be utilized for ALL therapy in future.

Whole-genome sequencing as a first-tier diagnostic framework for rare genetic diseases.

Rare diseases affect nearly 300 million people globally with most patients aged five or less. Traditional diagnostic approaches have provided much of the diagnosis; however, there are limitations. For instance, simply inadequate and untimely diagnosis adversely affects both the patient and their families. This review advocates the use of whole genome sequencing in clinical settings for diagnosis of rare genetic diseases by showcasing five case studies. These examples specifically describe the utilization of whole genome sequencing, which helped in providing relief to patients via correct diagnosis followed by use of precision medicine.

Evaluation and validation of tungsten fiducial marker-based image-guided radiotherapy.

In this research work, a simple homemade cubic phantom was designed to validate the Image-Guided Radiotherapy (IGRT) set up and verified with the help of tungsten fiducial markers (size 2-3 mm) inserted into the cubic phantom. Phantom made up of Styrofoam, was scanned with the help of 16 slice Toshiba CT scanner where each slice was of 1 mm thickness and HU level set to -1000. A radio-opaque contrast medium was rubbed on the phantom to visualize the scanner images. Once the iso-center had been marked on a phantom with the help of in-room positioning laser and the fields (RT-LAT and AP) were applied on the contoured body of the phantom in Varian's ARIA-11 Eclipse dosimeter software, the same position of the phantom was reproduced on Varian's Linear Accelerator DHX. Known shifts of 3.0 to 30.0 mm from the marked iso-center were applied on the phantom by moving the couch in all six directions one by one. On each applied couch shift, an x-ray image of the phantom was acquired with the help of an MV portal imager of Linac in AP and RT-LAT direction. This image was superimposed with a reference image of phantom and shift accuracy calculated by ARIA-11 software was noted down. It turned out that irrespective of the position of the phantom on the couch, the calculated corrected shift and deviation from reference position was always between ± 1-2 mm which is the required accuracy for IGRT according to International Atomic Energy Agency (IAEA). This process was repeated 40 times and each time, the corrected shift came out to be ± 1-2 mm. We can conclude that our system is safe and accurate enough to perfectly position the actual patient for IGRT.