Structure-function analysis of tight junction-directed permeation enhancer PIP250.

The intestinal paracellular route of absorption is modulated via tight junction (TJ) structures located at the apical neck of polarized intestinal epithelial cells to restrict solute movement through the intercellular space between them. Tight junctions open or close in response to changes in the phosphorylation status of light chain (MLC) at position Ser-19. This phosphorylation event is primarily controlled by MLC kinase (MLCK) and MLC phosphatase (MLCP), the latter being a holoenzyme that involves interaction between protein phosphatase 1 (PP1) and myosin targeting protein 1 (MYPT1).

Fine excipient materials in carrier-based dry powder inhalation formulations: The interplay of particle size and concentration effects.

The contributions of fine excipient materials to drug dispersibility from carrier-based dry powder inhalation (DPI) formulations are well recognized, although they are not completely understood. To improve the understanding of these contributions, we investigated the influences of the particle size of the fine excipient materials on characteristics of carrier-based DPI formulations. We studied two particle size grades of silica microspheres, with volume median diameters of 3.

A systematic review on understanding the mechanistic pathways and clinical aspects of natural CDK inhibitors on cancer progression.: Unlocking cellular and biochemical mechanisms.

Cell division, differentiation, and controlled cell death are all regulated by phosphorylation, a key biological function. This mechanism is controlled by a variety of enzymes, with cyclin-dependent kinases (CDKs) being particularly important in phosphorylating proteins at serine and threonine sites. CDKs, which contain 20 unique components, serve an important role in regulating vital physiological functions such as cell cycle progression and gene transcription.

Critical attributes of fine excipient materials in carrier-based dry powder inhalation formulations: The particle shape and surface properties.

The potential of fine excipient materials to improve the aerodynamic performance of carrier-based dry powder inhalation (DPI) formulations is well acknowledged but not fully elucidated. To improve the understanding of this potential, we studied two fine excipient materials: micronized lactose particles and silica microspheres. Inhalation formulations, each composed of a coarse lactose carrier, one of the two fine excipient materials (0.

Physician's Knowledge and Attitudes on Antibiotic Prescribing and Resistance: A Cross-Sectional Study from Hail Region of Saudi Arabia.

Background: Antibiotic (AB) resistance is caused partly by overuse, varies by region, and is influenced by prescriber perspectives. This study sought to determine physicians' knowledge and attitudes toward AB prescribing, particularly in the Hail region of Saudi Arabia.

Methods: An interdisciplinary team created and validated an electronic questionnaire via the test-retest method that measured reliability and consistency.

Artemisia sieberi Besser essential oil inhibits the growth and migration of breast cancer cells via induction of S-phase arrest, caspase-independent cell death and downregulation of ERK.

Ethnopharmacological Relevance: Artemisia sieberi Besser is a medicinal herb that has been traditionally used across the Middle East for the treatment of cancer. Further pharmacological studies on its extracts revealed that they possess cytotoxic activity against certain cancer cells, however, there were no studies conducted on the anticancer potential of Artemisia sieberi essential oil (ASEO).

Aim Of The Study: To evaluate the anticancer potential of ASEO, elucidate the oil's mode of action for the first time and investigate its chemical composition.

A comprehensive phytochemical, biological, and toxicological studies of roots and aerial parts of Buch.-Ham: An important medicinal plant.

This study was designed to seek the phytochemical analysis, antioxidant, enzyme inhibition, and toxicity potentials of methanol and dichloromethane (DCM) extracts of aerial and root parts of . Total bioactive content, high-performance liquid chromatography-photodiode array detector (HPLC-PDA) polyphenolic quantification, and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis were utilized to evaluate the phytochemical composition. Antioxidant [including 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH)], 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power assay (FRAP), cupric reducing antioxidant capacity CUPRAC, phosphomolybdenum, and metal chelation assays] and enzyme inhibition [against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, α-amylase, and tyrosinase] assays were carried out for biological evaluation.

Particle Engineering by Nano Spray Drying: Optimization of Process Parameters with Hydroethanolic versus Aqueous Solutions.

Nano spray drying has emerged as an outstanding platform for engineering micro- and nanoparticles, with growing applications in various areas of drug delivery. As a new technology involving distinct technical design, parameters of the nano spray drying process are not fully elucidated. In a quality-by-design approach, the aim of the current study was to gain thorough understanding of critical determinants of product characteristics in the Büchi Nano Spray Dryer B-90.

SARS-CoV-2 vaccines: Clinical endpoints and psychological perspectives: A literature review.

Background: About 270 million cases have been confirmed, and 5.3 million fatalities Worldwide due to SARS-CoV-2. Several vaccine candidates have entered phase 3 of the clinical trial and are being investigated to provide immunity to the maximum percentage of people.

Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects.

Experimental Design and Optimization of Nano-Transfersomal Gel to Enhance the Hypoglycemic Activity of Silymarin.

Current advancements in the research investigations focused at using natural products to generate novel dosage forms with a potential therapeutic impact. Silymarin is a natural product obtained from the herb that has been shown to have remarkable hypoglycemic activity. Owing to the low enteral absorption, instability in stomach secretion, and poor solubility of Silymarin, it was better to be produced as a topical dosage form.

Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device.

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler and the high resistance Handihaler as inhalation devices for spray-dried microparticles.

Elevated Levels of IL-33, IL-17 and IL-25 Indicate the Progression from Chronicity to Hepatocellular Carcinoma in Hepatitis C Virus Patients.

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma.

Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells.

Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from , has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner.

Development and Evaluation of Clove and Cinnamon Supercritical Fluid Extracts-Loaded Emulgel for Antifungal Activity in Denture Stomatitis.

Denture stomatitis (DS), usually caused by Candida infection, is one of the common denture-related complications in patients wearing dentures. Clove and cinnamon oils have been acknowledged for their anti-inflammatory, antimicrobial activity, and antifungal effects in the oral cavity. The aim of this study, therefore, was to prepare clove/cinnamon oils-loaded emulgel and to assess its efficacy in treating -associated denture stomatitis.

Alteration of Virulence and Host Pathogenesis through Targeting by Using the CRISPR-Cas9 System.

is a common cause of many enteric infections worldwide and is successfully engineered to deliver heterologous antigens to be used as vaccines. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 endonuclease is a promising genome editing tool. In the current study, a CRISPR-Cas9 system was used to target   that encodes signal molecule receptor SdiA and responds to the quorum sensing (QS) signaling compounds N-acylhomoserine lactones (AHLs).

Insights into the potential of rheological measurements in development of dry powder inhalation formulations.

Study of flow is a key to development of dry powder inhalation formulations. Various static (bulk) and dynamic rheological measurements are used to study different aspects of powder flow and packing. Among rheological measurements, the permeability and the fluidization energy are, conceptually, most relevant to dispersion of dry powder inhalation formulations.

Quality by Design for Optimizing a Novel Liposomal Jojoba Oil-Based Emulgel to Ameliorate the Anti-Inflammatory Effect of Brucine.

One of the recent advancements in research is the application of natural products in developing newly effective formulations that have few drawbacks and that boost therapeutic effects. The goal of the current exploration is to investigate the effect of jojoba oil in augmenting the anti-inflammatory effect of Brucine natural alkaloid. This is first development of a formulation that applies Brucine and jojoba oil int a PEGylated liposomal emulgel proposed for topical application.

Thymoquinone provides structural protection of human hemoglobin against oxidative damage: Biochemical studies.

Hydroxyl radicals (OH) are one of the most active reactive oxidants recognized for their deleterious effects to cause protein oxidative damage. Thymoquinone, a monoterpene molecule abundantly present in black cumin and known for its pharmacological activities, but its activity against the OH-induced protein oxidative damage has never been explored. This study determined the therapeutic potential of thymoquinone against OH-induced oxidative human hemoglobin damage.

An overview of SARS-COV-2 epidemiology, mutant variants, vaccines, and management strategies.

Background: Over the last two decades, humanity has observed the extraordinary anomaly caused by novel, weird coronavirus strains, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). As the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has made its entry into the world, it has dramatically affected life in every domain by continuously producing new variants. The vaccine development is an ongoing process, although some vaccines got marketed.

Playground lead levels in rubber, soil, sand, and mulch surfaces in Boston.

Rubber surfacing is often used in playgrounds due to its potential injury prevention benefits and as a way to recycle waste tires. Available research on chemicals in recycled rubber has focused on synthetic turf applications, but is limited for playground rubber surfacing. Potential lead contamination from vulcanizing agents used in rubber surfacing are a possible concern; however this has not been researched.

An intestinal paracellular pathway biased toward positively-charged macromolecules.

Lacking an effective mechanism to safely and consistently enhance macromolecular uptake across the intestinal epithelium, prospects for successful development of oral therapeutic peptide drugs remain unlikely. We previously addressed this challenge by identifying an endogenous mechanism that controls intestinal paracellular permeability that can be activated by a peptide, termed PIP 640, which can increase cellular levels of phosphorylated myosin light chain at position S (MLC-pS). Apical application in vitro or luminal application in vivo was shown to increase macromolecular solute transport within minutes that recovered completely within a few hours after removal.

Mechanistic studies of a cell-permeant peptide designed to enhance myosin light chain phosphorylation in polarized intestinal epithelia.

Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character.

Enhanced paracellular transport of insulin can be achieved via transient induction of myosin light chain phosphorylation.

The intestinal epithelium functions to effectively restrict the causal uptake of luminal contents but has been demonstrated to transiently increase paracellular permeability properties to provide an additional entry route for dietary macromolecules. We have examined a method to emulate this endogenous mechanism as a means of enhancing the oral uptake of insulin. Two sets of stable Permeant Inhibitor of Phosphatase (PIP) peptides were rationally designed to stimulate phosphorylation of intracellular epithelial myosin light chain (MLC) and screened using Caco-2 monolayers in vitro.