Formulation development and evaluation, in silico PBPK modeling and in vivo pharmacodynamic studies of clozapine matrix type transdermal patches.

Clozapine is a potent serotonin receptor antagonist and commonly used for the treatment of Schizophrenia. The study aimed to develop and optimize the transdermal matrix patch of clozapine. A 3-level, 3-factor Central Composite Design was applied to examine and validate the impact of various formulation variables, Eudragit, PEG, and oleic acid on in vitro drug release, flux, and tensile strength (TS).

Synergistic Effects of Hydrogen Peroxide Preconditioning and Valproic Acid on Hepatic Differentiation of Mesenchymal Stem Cells.

Introduction: Ex vivo preconditioning increases the therapeutic potential of mesenchymal stem cells (MSCs) in terms of antioxidant activity, growth factor production, homing, differentiation, and immunomodulation. Therefore, it is considered an effective strategy to be used before transplantation and therapeutic application of MSCs. Histone deacetylase inhibitor (HDACi), valproic acid (VPA), has been reported to induce hepatic differentiation in MSCs.

Synthesis of Temporin-SHa Retro Analogs with Lysine Addition/Substitution and Antibiotic Conjugation to Enhance Antibacterial, Antifungal, and Anticancer Activities.

In the face of rising the threat of resistant pathogens, antimicrobial peptides (AMPs) offer a viable alternative to the current challenge due to their broad-spectrum activity. This study focuses on enhancing the efficacy of temporin-SHa derived NST-2 peptide (), which is known for its antimicrobial and anticancer activities. We synthesized new analogs of using three strategies, i.

Potent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.

The search for effective anti-cancer therapies has led to the exploration of dual inhibition strategies targeting multiple key molecular pathways. In this study, we aimed to design a novel candidate capable of dual inhibition targeting both EGFR (Epidermal Growth Factor Receptor) and PARP-1 (poly(ADP-ribose)polymerase-1), two crucial proteins implicated in cancer progression and resistance mechanisms. Through molecular hybridization and structure-based drug design approaches, we synthesized a series of compounds based on spirooxindole with triazole scaffolds with the potential for dual EGFR and PARP-1 inhibition.

Efficacy of Intravenous Versus Oral Administration of Levocarnitine in Maintenance Hemodialysis Patients: A Randomized Controlled Trial Investigating Therapeutic Approaches to Renal Anemia.

Background And Aim: Carnitine deficiency contributes to various comorbidities in maintenance hemodialysis (MHD) patients. This study aims to assess the impact of levocarnitine supplementation on hematological and serum iron profile parameters, comparing the efficacy of oral versus intravenous (IV) administration in these patients.

Materials And Methods: This was a multicenter, randomized controlled trial was conducted on patients undergoing MHD at the hemodialysis unit of our study center in Karachi, Pakistan.

Applications of MicroED in structural biology and structure-based drug discovery.

Microcrystal electron diffraction (MicroED) is an emerging method for the structure determination of proteins and peptides, enzyme-inhibitor complexes. Several structures of biomolecules, including lysozyme, proteinase K, adenosine receptor A2A, insulin, xylanase, thermolysin, DNA, and Granulovirus occlusion bodies, have been successfully determined through MicroED. As MicroED uses very small crystals for structure determination, therefore, it has several advantages over conventional X-ray diffraction methods.

Insights into the salinity tolerance of the succulent halophyte : comparative ecophysiology of plants from heteromorphic seeds.

Introduction: Little is known about the similarities and differences in responses of plants grown from heteromorphic seeds, which are morpho-physiologically dissimilar seeds produced simultaneously on the same plant.

Methods: In this context, we studied how plants grown from heteromorphic (i.e.

Dancing Glycoproteins: Memory Pattern Formation by Protein Folding through Hydrogen Bonding.

A considerable amount of work has been carried out on the biology of learning and memory acquisition, and retention [1-6]; however, little is known regarding how the information is written in the brain [7-9]. It is notable that in the Neuron Theory postulated by Santiago Ramón y Cajal [10], neurons were conceived to form a contiguous instead of a continuous structure. They were physically separated but could function through their connections by synapses [11].

PPA1, TRIM68 and FBXO46: Potential Therapeutic Targets for Triple Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.

Perfecting prime editing: achieving precise edits in dicots.

Prime editing (PE), a precise CRISPR-based method, has worked well in some plants but faces challenges in dicots. Vu and colleagues developed new PE tools that greatly improve PE efficiency in dicots, enabling accurate, heritable genome edits. This advance marks a breakthrough that could revolutionize crop improvement and plant biotechnology.

Ascorbic acid-immobilized zinc selenide for electrochemical monitoring of hydrogen peroxide in liver cancer samples.

Liver cancer is globally the most frequent fatal malignancy, and its identification is critical for making clinical decisions about treatment options. Pathological diagnostics and contemporary imaging technologies provide insufficient information for tumor identification. Hydrogen peroxide (HO), an emerging biomarker is a powerful oxidant found in the tumor microenvironment, and stimulates the invasion, proliferation, and metastasis of liver cancer cells.

Comprehensive drug-like assessment of pyridine carbothioamide analogs: from molecular modeling to evaluation.

Aim: To evaluate the anti-inflammatory potential of novel class of chemical compounds designed by the linkage of carbothioamide moiety with pyridine.

Materials & Methods: In silico analysis was conducted using molecular docking followed by an in vitro cytotoxicity assay and evaluation of anti-inflammatory activity. Subsequently, in vivo performance was determined using the Complete Freund's Adjuvant-induced inflammatory model, employing macroscopic, histopathological, and protein expression analyses.

Exploring dihydropyrimidone derivatives as modulators of carbohydrate catabolic enzyme to mitigate diabetes.

Diabetes is a prevalent and serious metabolic disorder affecting millions globally, and it poses extensive health risks due to elevated blood glucose levels. One promising approach for managing diabetes is the inhibition of α-glucosidase, an enzyme that plays a crucial role in carbohydrate metabolism. Targeting α-glucosidase can help delay glucose absorption, thus controlling postprandial blood sugar spikes.

Clinical characteristics of dengue virus infections in Karachi from 2019 to 2023: a cross-sectional study.

Dengue fever is a vector-borne, acute, febrile, and self-limiting systemic viral infection that affects tropical and subtropical regions, including Pakistan. Karachi has a significant burden of Aedes aegypti and Aedes albopictus due to suitable breeding sites, weather, and rapid and unplanned urbanization of squatter areas. The country has limited surveillance studies on circulating serotypes of the dengue virus and the patient's clinical features evolving over temporal changes.

PX-12 modulates vorinostat-induced acetylation and methylation marks in CAL 27 cells.

Aim: The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells.

ALKBH5 promotes cardiac fibroblasts pyroptosis after myocardial infarction through Notch1/NLRP3 pathway.

Through bioinformatics screening, we previously found that AlkB homolog 5 (ALKBH5) expression, an mA demethylase, was higher in patients with heart failure than in the normal population. This study aimed to investigate the molecular mechanisms by which ALKBH5 regulates heart failure. We established a myocardial infarction (MI)-induced heart failure model in rats in vivo and an in vitro hypoxia model using rat primary cardiac fibroblasts (RCFs).

Pan-genome analysis and drug repurposing strategies for extensively drug-resistant Salmonella Typhi: Subtractive genomics and e-pharmacophore approaches.

In the current study, we presented the genome sequence and taxonomic classification of the new extensively drug-resistant (XDR) Salmonella enterica serovar Typhi strain JRCGR-ST-AK02. Its genome size was found to be 4,780,534 bp, containing 4864 genes. Taxonomic classification was performed based on the Average Nucleotide Identity (ANI), Genome-to-Genome Distance Calculator (GGDC) and Average Amino Acid Identity (AAI) analysis.

Synthesis of Gold Nanoparticles Using Cucurbitacin E-Glycoside and Methyl Gallate Isolated from Citrullus colocynthis L. Fruit and Evaluation of their Antibacterial and Antibiofilm Activities.

Introduction: Metal nanoparticles have received much attention due to their unique physical dynamics, chemical reactivity, and promising biological applications. Green synthesis using natural compounds is an alternative to traditional chemical methods for the synthesis of nanoparticles.

Materials And Methods: Herein, two secondary metabolites were isolated from different fractions of methanolic extract of Citrullus colocynthis (bitter apple) Schard.

Activated carbon cloth with MnCoAl layer double hydroxide nanocomposite for the separation and preconcentration of Pb(II) and Ni(II) from food samples.

A novel dispersive solid phase microextraction (dSP-ME) technique using activated carbon cloth (ACC) and layered double hydroxide (LDH) has been developed for enriching and extracting Pb(II) and Ni(II). The ACC@MnCoAl-LDH nanosorbent, has proven with high surface area, superior extraction dynamics and efficiency, compared to traditional sorbents. Structural features of the new ACC@MnCoAl-LDH sorbent were also characterized.

Combination of Biogas Residues and Interactions Stimulates Crop Production and Salinity Tolerance in .

Stress tolerance in cereal crops like Sorghum is important to address food security and land development for saline agriculture. Salinity is considered one of the most devastating abiotic stresses affecting plant growth and yield, specifically in water-scared areas of the world. Biogas residue is a good source of plant nutrients with enriched fertilizer for crop yield and productivity.

Workplace Cyberbullying: Nature, Characteristics, and Implications.

The information technology revolution has fundamentally altered company operations around the world. The Internet has significantly enhanced employee connectedness in the workplace, eclipsing the antiquated brick-and-mortar model. Nonetheless, as information technology advances, cyberbullying has grown in popularity in the professional environment.

Identification of dimethyl 2,2'-((methylenebis(2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)-6,1phenylene))bis(oxy))diacetate (TAJ4) as antagonist of NEK-Family: a future for potential drug discovery.

The purpose of the current study was to analyze and validate the existing gap in knowledge, by conducting a differential expression analysis and validation of NEK6, NEK7, and NEK9 in breast, cervical, and glioblastoma cancer and targeting these proteins through development of novel site specific inhibitor with favorable pharmacokinetic and safety profile, using open-source databases. The analysis revealed that the targeted kinases were overexpressed in all three types of cancer. Their expression was significantly linked to overall survival rates, which suggests that they play a major role in the development and progression of these cancers.

Pharmacological investigation of selected 1,2,4 triazole derivative against ethanol induced gastric ulcer.

The present study aims to assess the therapeutic potential of (2S,3S,4S,5S,6S-2-(acetoxymethyl)-6-(4-chlorophenyl)-3-(pyridine-4-yl)5-thioxo-4,5-dihydro-1,2,4-triazol-1-yl tetrahydro-2H-pyran 3,4,5tryltriacetate (JAK05) on gastric ulcer. The current study was designed to evaluate the anti-ulcer potential of JAK05 against ethanol-induced gastric ulcer by employing in silico, in vitro and in vivo techniques. In silico studies, JAK05 has a binding score ranging from -8.

Cypsela and Pappus Morphology and Their Significance for the Taxonomic Delimitation of the Genus DC. .. and Its Allied Genera (Asteraceae).

The cypsela and pappus macro- and micromorphological features of 32 taxa belonging to DC. ., Kamelin, Raab-Straube, DC.