Discovery of Novel PTP1B Inhibitors by High-throughput Virtual Screening.

AIM: To Discover novel PTP1B inhibitors by high-throughput virtual screening Background: Type 2 Diabetes is a significant global health concern. According to projections, the estimated number of individuals affected by the condition will reach 578 million by the year 2030 and is expected to further increase to 700 million deaths by 2045. Protein Tyrosine Phosphatase 1B is an enzymatic protein that has a negative regulatory effect on the pathways involved in insulin signaling. This regulatory action ultimately results in the development of insulin resistance and the subsequent elevation of glucose levels in the bloodstream. The proper functioning of insulin signaling is essential for maintaining glucose homeostasis, whereas the disruption of insulin signaling can result in the development of type 2 diabetes. Consequently, we sought to utilize PTP1B as a drug target in this investigation. OBJECTIVE: The purpose of our study was to identify novel PTP1B inhibitors as a potential treatment for managing type 2 diabetes. METHODS: To discover potent PTP1B inhibitors, we have screened the Maybridge HitDiscover database by SBVS. Top hits have been passed based on various drug-likeness rules, toxicity predictions, ADME assessment, Consensus Molecular docking, DFT, and 300 ns MD Simulations. RESULTS: Two compounds have been identified with strong binding affinity at the active site of PTP1B along with drug-like properties, efficient ADME, low toxicity, and high stability. CONCLUSION: The identified molecules could potentially manage T2DM effectively by inhibiting PTP1B, providing a promising avenue for therapeutic strategies.

Liquid Crystalline Lipid Nanoparticles: Emerging Trends and Applications in Skin Cancer.

Liquid crystalline lipid nanoparticles (LCNPs) represent a type of membrane-based nano-carriers formed through the self-assembly of lyotropic lipids. These lipids, such as unsaturated monoglycerides, phospholipids, and co-lipids, create liquid crystals or vesicles with an aqueous core enclosed by a natural or synthetic phospholipid bilayer upon exposure to an aqueous medium. Liquid crystalline lipid nanoparticles (LCNPs), akin to liposomes, have garnered significant attention as nanocarriers suitable for a diverse range of hydrophobic and hydrophilic molecules. Their notable structural advantage lies in a mono-channel network organization and the presence of multiple compartments, resulting in heightened encapsulation efficiency for various substances. Cubosomes, spongosomes, hexosomes, and multicompartment nanoparticles are examples of lipid nanocarriers with interior liquid crystalline structures that have recently gained a lot of interest as effective drug delivery systems. Additionally, LCNPs facilitate the sustained release of encapsulated compounds, including therapeutic macromolecules. This review delves into the structure of liquid crystalline lipid nanoparticles, explores preparation techniques, and outlines their applications in the context of skin cancer.

Recent Research Trends against Skin Carcinoma - An Overview.

Skin cancer is a prevalent and sometimes lethal cancer that affects a wide range of people. UV radiation exposure is the main cause of skin cancer. Immunosuppression, environmental factors, and genetic predisposition are other contributing variables. Fair-skinned people and those with a history of sunburns or severe sun exposure are more likely to experience this condition. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are the three main forms. Melanoma poses a bigger hazard because of its tendency for metastasis, while SCC and BCC have limited metastatic potential. Genetic mutations and changes to signalling pathways such as p53 and MAPK are involved in pathogenesis. Early diagnosis is essential, and molecular testing, biopsy, dermoscopy, and visual inspection can all help. In addition to natural medicines like curcumin and green tea polyphenols, treatment options include immunotherapy, targeted therapy, radiation, surgery, and chemotherapy. Reducing the incidence of skin cancer requires preventive actions, including sun protection and early detection programs. An overview of skin cancers, including their forms, pathophysiology, diagnosis, and treatment, highlighting herbal therapy, is given in this review.

Glycerosomes: Novel Nano-Vesicles for Efficient Delivery of Therapeutics.

BACKGROUND: The topical drug delivery system has gained more attention in recent years as compared to oral and parenteral drug delivery. However, owing to the barrier function of the skin's topmost layer, only a few drug molecules can be administered by this route. Therefore, encapsulating the drugs in glycerosomes is one potential solution to this problem. Glycerosomes are vesicular drug delivery systems primarily made up of large concentrations of glycerol, phospholipid, water, and other active ingredients. OBJECTIVE: The main aim of this review is to summarize the most recent information on the encapsulated vesicular system used in cosmetic preparations, specifically glycerosomes made from both synthetic and naturally occurring plant bioactive substances. PURPOSE: Glycerosomes offer many benefits, including increased efficacy, better stability, improve absorption, drug targeting at specific sites, and delivering the same at a predetermined rate. METHOD: The mechanism behind the penetration of glycerosomes is the hydration and lipid fluidization of skin, fabricated by glycerol. RESULT: Numerous methods have been reported for the formulation of glycerosomes, including the thin film hydration method, reverse-phase evaporation, solvent spherule, detergent removal method, and so on. CONCLUSION: Researchers are currently investigating the potential of glycerosomes as nanocarriers for natural bioactive and synthetic drugs. This review describes the structure of glycerosomes, preparation techniques, applications, distinctions from liposomes, and benefits of glycerosomes.

Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update.

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the ß cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

Cancer Proteomics for Cellular Dysfunction: Insights and Trends.

BACKGROUND: Cancer is an ailment with having a very low survival rate globally. Poor cancer prognosis is primarily caused by the fact that people are found to have the disease when it is already well advanced. The goal of this study is to compile information on new avenues of investigation into biomarkers that may facilitate the routine detection of cancer. Proteomic analysis has recently developed into a crucial technique for cancer biology research, working in tandem with genomic analysis. Mass spectrometry techniques are one of several proteome analysis techniques that allow for the highly precise quantitative and qualitative recognition of hundreds of proteins in small quantities from various biological materials. These findings might soon serve as the foundation for better cancer diagnostic techniques. METHODS: An exhaustive literature survey has been conducted using electronic databases such as Google Scholar, Science Direct, and PubMed with keywords of proteomics, applications of proteomics, the technology of proteomics, biomarkers, and patents related to biomarkers. RESULT: Studies reported till 2021 focusing on cancer proteomics and the related patents have been included in the present review to obtain concrete findings, highlighting the applications of proteomics in cancer. CONCLUSION: The present review aims to present the overview and insights into cancer proteomics, recent breakthroughs in proteomics techniques, and applications of proteomics with technological advancements, ranging from searching biomarkers to the characterization of molecular pathways, though the entire process is still in its infancy.

Interventions to reduce Staphylococcus aureus in the management of eczema.

BACKGROUND: Staphylococcus aureus (S. aureus) can cause secondary infection in eczema, and may promote inflammation in eczema that does not look infected. There is no standard intervention to reduce S. aureus burden in eczema. It is unclear whether antimicrobial treatments help eczema or promote bacterial resistance. This is an update of a 2008 Cochrane Review. OBJECTIVES: To assess the effects of interventions to reduce S. aureus for treating eczema. SEARCH METHODS: We updated our searches of the following databases to October 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched five trials registers and three sets of conference proceedings. We checked references of trials and reviews for further relevant studies. We contacted pharmaceutical companies regarding ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials of products intended to reduce S. aureus on the skin in people diagnosed with atopic eczema by a medical practitioner. Eligible comparators were a similar treatment regimen without the anti-staphylococcal agent. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were participant- or assessor-rated global improvement in symptoms/signs, quality of life (QOL), severe adverse events requiring withdrawal, minor adverse events, and emergence of antibiotic-resistant micro-organisms. MAIN RESULTS: We included 41 studies (1753 analysed participants) covering 10 treatment categories. Studies were conducted mainly in secondary care in Western Europe; North America; the Far East; and elsewhere. Twelve studies recruited children; four, adults; 19, both; and six, unclear. Fifty-nine per cent of the studies reported the mean age of participants (range: 1.1 to 34.6 years). Eczema severity ranged from mild to severe. Many studies did not report our primary outcomes. Treatment durations ranged from 10 minutes to 3 months; total study durations ranged from 15 weeks to 27 months. We considered 33 studies at high risk of bias in at least one domain. We present results for three key comparisons. All time point measurements were taken from baseline. We classed outcomes as short-term when treatment duration was less than four weeks, and long-term when treatment was given for more than four weeks. Fourteen studies evaluated topical steroid/antibiotic combinations compared to topical steroids alone (infective status: infected (two studies), not infected (four studies), unspecified (eight studies)). Topical steroid/antibiotic combinations may lead to slightly greater global improvement in good or excellent signs/symptoms than topical steroid alone at 6 to 28 days follow-up (risk ratio (RR) 1.10, 95% confidence interval (CI) 1.00 to 1.21; 224 participants; 3 studies, low-quality evidence). There is probably little or no difference between groups for QOL in children, at 14 days follow-up (mean difference (MD) -0.18, 95% CI -0.40 to 0.04; 42 participants; 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: severe adverse events were rare (follow-up: between 6 to 28 days): both groups reported flare of dermatitis, worsening of the condition, and folliculitis (325 participants; 4 studies). There were fewer minor adverse events (e.g. flare, stinging, itch, folliculitis) in the combination group at 14 days follow-up (218 participants; 2 studies). One study reported antibiotic resistance in children at three months follow-up, with similar results between the groups (65 participants; 1 study). Four studies evaluated oral antibiotics compared to placebo (infective status: infected eczema (two studies), uninfected (one study), one study's participants had colonisation but no clinical infection). Oral antibiotics may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo (RR 0.80; 95% CI 0.18 to 3.50; 75 participants; 2 studies, low-quality evidence). There is probably little or no difference between groups for QOL (in infants and children) at 14 days follow-up (MD 0.11, 95% CI -0.10 to 0.32, 45 participants, 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: adverse events requiring treatment withdrawal between 14 to 28 days follow-up were very rare, but included eczema worsening (both groups), loose stools (antibiotic group), and Henoch-Schönlein purpura (placebo group) (4 studies, 199 participants). Minor adverse events, including nausea, vomiting, diarrhoea, and stomach and joint pains, at 28 days follow-up were also rare and generally low in both groups (1 study, 68 infants and children). Antibiotic resistance at 14 days was reported as similar in both groups (2 studies, 98 infants and children). Of five studies evaluating bleach baths compared to placebo (water) or bath emollient (infective status: uninfected (two studies), unspecified (three studies)), one reported global improvement and showed that bleach baths may make no difference when compared with placebo at one month follow-up (RR 0.78, 95% CI 0.37 to 1.63; 36 participants; low-quality evidence). One study showed there is probably little or no difference in QOL at 28 days follow-up when comparing bleach baths to placebo (MD 0.90, 95% CI -1.32 to 3.12) (80 infants and children; moderate-quality evidence). We are uncertain if the groups differ in the likelihood of treatment withdrawals due to adverse events at two months follow-up (only one dropout reported due to worsening itch (placebo group)) as the quality of evidence was very low (1 study, 42 participants). One study reported that five participants in each group experienced burning/stinging or dry skin at two months follow-up, so there may be no difference in minor adverse events between groups (RR 1.00, 95% CI 0.35 to 2.87, 36 participants, low-quality evidence). Very low-quality evidence means we are also uncertain if antibiotic resistance at four weeks follow-up is different between groups (1 study, 80 participants ≤ 18 years). AUTHORS' CONCLUSIONS: We found insufficient evidence on the effects of anti-staphylococcal treatments for treating people with infected or uninfected eczema. Low-quality evidence, due to risk of bias, imprecise effect estimates and heterogeneity, made pooling of results difficult. Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required.

Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma.

The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.