Unraveling the molecular basis for effective regulation of integrin α5ß1 for enhanced therapeutic interventions.

Cell attachment to the extracellular matrix significantly impacts the integrity of tissues and human health. The integrin α5ß1 is a heterodimer of α5 and ß1 subunits and has been identified as a crucial modulator in several human carcinomas. Integrin α5ß1 significantly regulates cell proliferation, angiogenesis, inflammation, tumor metastasis, and invasion. This regulatory role of integrin α5ß1 in tumor metastasis makes it an appealing target for cancer therapy. The majority of the drugs targeting integrin α5ß1 are limited only to clinical trials. In our study, we have performed 94287 compounds screening to determine potential drugs against α5ß1 integrin. We have used ATN-161 as a reference and employed combined bioinformatic methodologies, including molecular modelling, virtual screening, MM-GBSA, cell-line cytotoxicity prediction, ADMET, Density Functional Theory (DFT), Non-covalent Interactions (NCI) and molecular simulation, to identify putative integrin α5ß1 inhibitors. We found Taxifolin, PD133053, and Acebutolol that possess inhibitory activity against α5ß1 integrin and could act as effective drug for the cancer treatment. Taxifolin, PD133053, and Acebutolol exhibited excellent binding to the druggable pocket of integrin α5ß1, and also maintained a unique binding mechanism with extra hydrophobic contacts at molecular level. Overall, our study gives new pharmacological candidates that may act as a potential drug against integrin α5ß1.

Exploring flavonoid derivatives as potential pancreatic lipase inhibitors for obesity management: An in silico and in vitro study.

Obesity is widely recognized as a major public health issue and is one of the leading causes of death worldwide. Overweight and obesity are prominent lifestyle ailments that not only give rise to additional health issues but also play a role in the development of other chronic diseases, such as cancer, diabetes, metabolic syndrome, and cardiovascular diseases. Orlistat is now the only pharmaceutical drug for the management of obesity. However, prolonged use of orlistat has been associated with detrimental consequences, hence necessitating the development of a new drug with reduced or no adverse reactions. Pancreatic Lipase is a critical enzyme in lipid metabolism. Using naturally occurring compounds as PL inhibitors has garnered significant attention because of their diverse structure and low toxicity. The present work investigates the inhibitory action of flavonoids on PL using in silico and in vitro methods. Thirteen flavonoid derivatives and orlistat were docked with PL. The ADME properties of the flavonoid derivatives were studied, and most of the compounds are in admire range. The stability of the best-docked complexes was checked by REMD. The in silico study demonstrated favorable inhibitory activity of flavonoids compared to orlistat. Consequently, an enzyme inhibitory experiment was conducted to authenticate the in silico results. The lipase inhibitory activity was assessed by using p-nitrophenyl butyrate as the substrate. Kaempferol exhibited significant inhibitory activity against PL, as shown by its IC50 value of 72.7 ± 3 µM. This study proposed a natural drug candidate with promising inhibitory efficacy against PL for obesity.

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications.

Copper(I)-catalyzed 1,3-dipolar cycloaddition between organic azides and terminal alkynes, commonly known as CuAAC or click chemistry, has been identified as one of the most successful, versatile, reliable, and modular strategies for the rapid and regioselective construction of 1,4-disubstituted 1,2,3-triazoles as diversely functionalized molecules. Carbohydrates, an integral part of living cells, have several fascinating features, including their structural diversity, biocompatibility, bioavailability, hydrophilicity, and superior ADME properties with minimal toxicity, which support increased demand to explore them as versatile scaffolds for easy access to diverse glycohybrids and well-defined glycoconjugates for complete chemical, biochemical, and pharmacological investigations. This review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides, glycoproteins, glycolipids, glycoclusters, and glycodendrimers through regioselective triazole forming modular and bio-orthogonal coupling protocols). It discusses the widespread applications of these glycoproducts as enzyme inhibitors in drug discovery and development, sensing, gelation, chelation, glycosylation, and catalysis. This review also covers the impact of click chemistry and provides future perspectives on its role in various emerging disciplines of science and technology.

QbD-assisted development of lipidic nanocapsules for antiestrogenic activity of exemestane in breast cancer.

Some breast cancers are caused by hormonal imbalances, such as estrogen and progesterone. These hormones play a function in directing the growth of cancer cells. The hormone receptors in hormone receptor-positive breast cancer lead breast cells to proliferate out of control. Cancer therapy such as hormonal, targeted, radiation is still unsatisfactory because of these challenges namely multiple drug resistance (MDR), off-targeting, severe adverse effects. A novel aromatase inhibitor exemestane (Exe) exhibits promising therapy in breast cancer. This study aims to develop and optimize Exe-loaded lipid nanocapsules (LNCs) by using DSPC, PF68 and olive oil as lipid, surfactant and oil phase, respectively and to characterize the same. The prepared nanocapsules were investigated via in vitro cell culture and in vivo animal models. The LNCs exhibited cytotoxicity in MCF-7 cell lines and enhanced anti-cancer activity and reduced cardiotoxicity in DMBA-induced animal model when compared to the drug. Additionally, in vivo pharmacokinetics revealed a 4.2-fold increased oral bioavailability when compared with Exe suspension. This study demonstrated that oral administration of Exe-loaded LNCs holds promise for the antiestrogenic activity of exemestane in breast cancer.

Assessment of anti-arthritic activity of lipid matrix encased berberine in rheumatic animal model.

The purpose of this study was to evaluate the drug delivery and therapeutic potential of berberine (Br) loaded nanoformulation in rheumatoid arthritis (RA)-induced animal model. The Br-loaded NLCs (nanostructured lipid carriers) were prepared employing melt-emulsification process, and optimised through Box-Behnken design. The prepared NLCs were assessed for in-vitro and in-vivo evaluations. The optimised NLCs exhibited a mean diameter of 180.2 ± 0.31 nm with 88.32 ± 2.43% entrapment efficiency. An enhanced anti-arthritic activity with reduced arthritic scores to 0.66 ± 0.51, reduction in ankle diameter to 5.80 ± 0.27 mm, decline in paw withdrawal timing, and improvements in walking behaviour were observed in the Br-NLCs treated group. The radiographic images revealed a reduction in bone and cartilage deformation. The Br-NLCs showed promising results in the management of RA disease, can be developed as an efficient delivery system at commercial levels, and may be explored for clinical application after suitable experiments in the future.

Identification of Severe Acute Respiratory Syndrome Coronavirus-2 inhibitors through in silico structure-based virtual screening and molecular interaction studies.

The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or COVID-19 has caused a worldwide pandemic. The fatal virus has affected the health of human beings as well as the socio-economic situation all over the world. To date, no concrete medicinal solution has been proposed to combat the viral infection, calling for an urgent, strategic, and cost-effective drug development approach that may be achievable by applying targeted computational and virtual screening protocols. Immunity is the body's natural defense against disease-causing pathogens, which can be boosted by consuming plant-based or natural food products. Active constituents derived from natural sources also scavenge the free radicals and have anti-inflammatory activities. Herbs and spices have been used for various medicinal purposes. In this study, 2,96 365 natural and synthetic derivatives (ligands) belonging to 102 classes of compounds were obtained from PubChem and assessed on Lipinski's parameters for their potential bioavailability. Out of all the derivatives, 3254 obeyed Lipinski's rule and were virtually screened. The 115 top derivatives were docked against SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-HKV1 main proteases (Mpro s) as receptors using AutoDock Vina, AutoDock, and iGEMDOCK 2.1. The lowest binding energy was exhibited by ligands 2 and 6 against all the four Mpro s. The molecular dynamic simulation was also performed with ligand 6 using the GROMACS package. Good bioactivity scores, absorption, distribution, metabolism, excretion, and toxicity profile and drug-like pharmacokinetic parameters were also obtained. Hydroxychloroquine was used as the control drug.

Fabrication of Imatinib Mesylate-Loaded Lactoferrin-Modified PEGylated Liquid Crystalline Nanoparticles for Mitochondrial-Dependent Apoptosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of concern as it has substantial morbidity associated with it. Previous reports have ascertained the antiproliferative activity of imatinib mesylate (IMS) against diverse types of carcinomas, but limited bioavailability has also been reported. The present study envisaged optimized IMS-loaded lactoferrin (LF)-modified PEGylated liquid crystalline nanoparticles (IMS-LF-LCNPs) for effective therapy of IMS to HCC via asialoglycoprotein receptor (ASGPR) targeting. Results displayed that IMS-LF-LCNPs presented an optimum particle size of 120.40 ± 2.75 nm, a zeta potential of +12.5 ± 0.23 mV, and 73.94 ± 2.69% release. High-resolution transmission electron microscopy and atomic force microscopy were used to confirm the surface architecture of IMS-LF-LCNPs. The results of cytotoxicity and 4,6-diamidino-2-phenylindole revealed that IMS-LF-LCNPs had the highest growth inhibition and significant apoptotic effects. Pharmacokinetics and biodistribution studies showed that IMS-LF-LCNPs have superior pharmacokinetic performance and targeted delivery compared to IMS-LCNPs and plain IMS, which was attributed to the targeting action of LF that targets the ASGPR in hepatic cells. Next, our in vivo experiment established that the HCC environment existed due to suppression of BAX, cyt c, BAD, e-NOS, and caspase (3 and 9) genes, which thus owed upstream expression of Bcl-xl, iNOS, and Bcl-2 genes. The excellent therapeutic potential of IMS-LF-LCNPs began the significant stimulation of caspase-mediated apoptotic signals accountable for its anti-HCC prospect. 1H nuclear magnetic resonance (serum) metabolomics revealed that IMS-LF-LCNPs are capable of regulating the disturbed levels of metabolites linked to HCC triggered through N-nitrosodiethylamine. Therefore, IMS-LF-LCNPs are a potentially effective formulation against HCC.

Glycosyl Triazole Ligand for Temperature-Dependent Competitive Reactions of Cu-Catalyzed Sonogashira Coupling and Glaser Coupling.

Glycosyl triazoles have been introduced as efficient ligands for the Cu-catalyzed Sonogashira reaction to overcome the challenges of sideways homocoupling reactions in Cu catalysis in this reaction. The atmospheric oxygen in a sealed tube did not affect the coupling, and no need of complete exclusion of oxygen was experienced in the presence of glycohybrid triazole ligand L3. High product yields were obtained at 130 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted aromatic halides including 9-bromo noscapine. In contrast, at room temperature, a very low loading of the L3-Cu catalytic system could produce excellent yields in Glaser coupling including homocoupling and heterocoupling of a variety of aliphatic and aromatic alkynes.

Virtual screening, ADME/T, and binding free energy analysis of anti-viral, anti-protease, and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2.

Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from -6.8 to -5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research.HighlightsNSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs.NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions.Compounds show good DG binging free energy with protein complexes.Ligands were found to follow the Lipinski rule of five.

In vitro and in silico molecular interaction of multiphase nanoparticles containing inositol hexaphosphate and jacalin: Therapeutic potential against colon cancer cells (HCT-15).

Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer.

Optimization of Inositol Hexaphosphate Colon Targeted Formulation for Anticarcinogenic Marker Modulation.

Colorectal cancer has become the third most frequent reason of cancer death in men and women. Currently, natural compounds are being looked up to, for subversion and deterrence of cancers. Inositol hexaphosphate (IP6) is one such naturally occurring phosphorylated carbohydrate present in most legumes and cereals which acts as a potential antineoplastic agent and can be used effectively to prevent and treat colon carcinomas. Despite the immense potential, due to the prevalence of high charge and ability to form salts and chelates with various divalent metals, it gets excreted out quickly from the body. On reaching the colon in its original form, it can serve as an effective anticancer agent. Therefore, a suitable dosage form that can prevent the drugs from being absorbed from the upper gastrointestinal tract is required to be prepared, to target it to the colon. Thus, microspheres of IP6 using a biodegradable polymer that degrades in the colon were attempted using the solvent evaporation method. The formulation was investigated for percentage yield, encapsulation efficiency, particle size distribution modification, and release rate. Optimized formulation showed particle size of 92 ± 0.76 µm, entrapment efficiency of 67.26% ± 0.75, percent drug loading of 15.74%, and in vitro drug release 82.36 ± 0.51. The results of the in vivo study divulged that IP6 loaded pectin microspheres showed significant positive modulation of biomarker levels and restoration of colonic architecture to almost normal as observed through histopathology and scanning electron microscopy studies in DMH-induced colon tumors in Albino Wistar rats.

Cu-Catalyzed Click Reaction in Carbohydrate Chemistry.

Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the "click reaction", serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.

Polysaccharide Encrusted Multilayered Nano-Colloidal System of Andrographolide for Improved Hepatoprotection.

Andrographolide (AP), a phytoconstituent of Andrographis paniculata is reported as a potent hepatoprotective agent. However, utility of this molecule is restricted due to its low aqueous solubility, gastric instability and hence low bioavailability. It was aimed to formulate and characterize AP-loaded, natural biopolymer stabilized, multilayered nano-hydrocolloid delivery system. Nanoemulsion (NE) was formulated using layer-by-layer (LbL) technology via electrostatic deposition of chitosan over alginate encrusted o/w NE by ultra-sonication. Improved transparency and stability of NE were observed with increasing sonication time. Best stability was obtained after 20 min sonication and particle size of the multilayered NE was measured in the range of 90.8-167.8 nm. Transmission electron microscopy confirmed the progressive layering of nanosized NE. Higher magnitude of zeta potential (i.e., 22.9 to 31.01 mV) confirmed higher stability and coating of alginate layer over NE surface for the period of 3 months. NE showed strategic release pattern when assessed in vitro in various simulated biological fluids of GIT in timed pattern. Multilayered NE showed significant modulation in liver function test (ALT, ALP, AST, TBIL, DBIL, and liver glycogen) and serum cytokines (TNF-α, IL-6, IL-10, and IL-ß) when assessed in vivo in galactosamine-lipopolysaccharide intoxicated mice. In conclusion, the andrographolide engrained multi-layered NE enhanced the solubility, stability and henceforth assured the increased availability in simulated biological fluids. The in vivo study exhibited the significantly improved hepatoprotection by andrographolide when delivered in stable multi-layered NE carrier systems.

Development, optimization, and characterization of a novel tea tree oil nanogel using response surface methodology.

PURPOSE: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO). METHODOLOGY: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37 °C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains. RESULTS AND DISCUSSION: Optimized NE had particle size and zeta potential of 16.23 ± 0.411 nm and 36.11 ± 1.234 mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57 ± 0.05 ) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58 µL/cm(2)) and flux value (JSS) of 7.96 µL cm(2)/h through skin in 10 h. Viscosity and texture parameters, firmness (9.3 ± 0.08 g), spreadability (2.26 ± 0.06 mJ), extrudability (61.6 ± 0.05 mJ), and adhesiveness (8.66 ± 0.08 g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d. CONCLUSION: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.

Encapsulation of Mentha Oil in Chitosan Polymer Matrix Alleviates Skin Irritation.

Mentha spicata L. var. viridis oil (MVO) is a potent antifungal agent, but its application in the topical treatment is limited due to its irritancy and volatility. It was aimed to develop more efficient, chitosan-incrusted MVO microspheres with reduced volatility and lesser irritancy and to dispense it in the form of ointment. Simple coacervation technique was employed to microencapsulate MVO in chitosan matrix. Morphological properties and polymer cross-linking were characterized by scanning electron microscopy and differential scanning calorimetry, respectively. Optimization was carried out on the basis of entrapment efficiency (EE) using response surface methodology. Well-designed microspheres having smooth surface and spherical shape were observed. EE (81.20%) of optimum batch (R21) was found at 1.62% w/v of cross-linker, 5.4:5 of MVO to chitosan ratio and at 1000 rpm. R21 showed 69.38 ± 1.29% in vitro MVO release in 12 h and 96.92% retention of MVO in microspheres even after 8 week. Ointments of PEG 4000 and PEG 400 comprising MVO (F1) and R21 (F2) were developed separately. F2 showed comparatively broader zone of growth inhibition (13.33 ± 1.76-18.67 ± 0.88 mm) and less irritancy (PII 0.5833, irritation barely perceptible) than that of F1. F2 was able to avoid the direct contact of mild irritant MVO with the skin and to reduce its rapid volatility. Controlled release of MVO helped in lengthening the duration of availability of MVO in agar media and hence improved its therapeutic efficacy. In conclusion, a stable and non-irritant formulation with improved therapeutic potential was developed.

An In Silico Study on Withania somnifera Bioactives and Curcumin Analogs as Potential Inducers of Smoothened (Smo) Receptor of Sonic Hedgehog (SHH) Pathway to Promote Oligodendrogenesis.

Demyelinating disorder is a subset of neurodegenerative conditions wherein factors such as aging and/or auto-immune attack cause damage and degradation of myelin sheath which enwraps the neuronal axons. Lowered axonal integrity and sub-par conduction of nerve impulses due to impaired action potentials make neurodegeneration imminent as the neurons do not have mitotic ability to replenish their numbers. Oligodendrocytes (OLs) myelinate the axonal segments of neurons and perform neuronal maintenance. Neuroregenerative stem cell therapy exploits this property for remyelination by targeting OL replenishment using in vitro stem cell differentiation protocols for inducing OL lineage cells. But some shortcomings of such protocols are over-reliance on synthetic inducers, lengthy differentiation process, low differentiation efficiency besides being financially expensive. This in silico study sought to identify herbal substitutes of currently available OL-lineage-specific synthetic inducers from a virtual library of curcumin analogs and Withania somnifera bioactives. Smoothened (Smo) receptor belonging to the canonical sonic hedgehog (SHH) signaling pathway promotes in vivo differentiation of OLs as well as their subsequent lineage progression to myelinating OLs. Therefore, we performed pharmacokinetics prediction for the bioactives followed by their molecular docking and molecular dynamics simulation with Smo. From a pool of 1289 curcumin analogs and 80 Withania somnifera-derived bioactives, the best docked ligands were identified as the compounds with PubChem IDs 68815167 and 25880, respectively. Molecular dynamics simulation of these ligands further concluded the Withania somnifera bioactive 25880 to have the best activity with Smo. This compound may be deemed as a potential lead molecule for an agonistic interaction with and activation of Smo to initialize its downstream signaling cascade for enriching OL differentiation.

Regulating pri/pre-microRNA up/down expressed in cancer proliferation, angiogenesis and metastasis using selected potent triterpenoids.

MicroRNAs (miRNAs) play a crucial role in cancer progression by selectively inducing translational degradation of messenger RNA (mRNA) via sequence-specific interactions with the 3'-untranslated region (3'-UTR). The potential targeting of miRNA has been recognized as a significant avenue for investigating the biological progression of diverse cancer types. Consequently, targeting of pri-miRNA and pre-miRNA by phytochemicals emerges as a viable strategy in the realm of anticancer therapies. Among phytochemicals, triterpenoids have garnered significant recognition for their chemotherapeutic and chemopreventive capabilities in combating multiple cancers. To date, there is a dearth of literature about the molecular interactions between triterpenoids and miRNAs. The primary objective of this investigation is to discern the potential triterpenoids that can function as modulators for specific miRNAs, namely pri-miRNA-19b-2, pre-miR21, microRNA 20b, pri-miRNA-208a, pri-miRNA-378a, pri-miRNA-320b-2, and pri-miRNA-300, achieved through the use of in silico investigations. The study primarily focused on performing drug-likeness, computer-aided toxicity, and pharmacokinetic prediction studies for triterpenoids. Furthermore, molecular docking and simulation techniques were employed to investigate these compounds. The triterpenoids studied were shown to have drug-likeness characteristics, although asiatic acid, lupeol, and pristimerin were able to pass all toxicity tests. Among the triterpenoids that underwent docking, pristimerin had a significant binding energy of -10.9 kcal/mol during its interaction with pri-miR-378a. The stable interaction between the pristimerin and miRNA complex was demonstrated by molecular dynamics simulation. As a result, pristimerin has the potential to act as a modulator of carcinogenic miRNAs, making it a promising candidate for cancer prevention and treatment due to its tailored modulation of miRNA activity.

Development of pH-Sensitive hydrogel for advanced wound Healing: Graft copolymerization of locust bean gum with acrylamide and acrylic acid.

Wounds pose a formidable challenge in healthcare, necessitating the exploration of innovative tissue-healing solutions. Traditional wound dressings exhibit drawbacks, causing tissue damage and impeding natural healing. Using a Microwave (MW)-)-assisted technique, we envisaged a novel hydrogel (Hg) scaffold to address these challenges. This hydrogel scaffold was created by synthesizing a pH-responsive crosslinked material, specifically locust bean gum-grafted-poly(acrylamide-co-acrylic acid) [LBG-g-poly(AAm-co-AAc)], to enable sustained release of c-phycocyanin (C-Pc). Synthesized LBG-g-poly(AAm-co-AAc) was fine-tuned by adjusting various synthetic parameters, including the concentration of monomers, duration of reaction, and MW irradiation intensity, to maximize the yield of crosslinked LBG grafted product and enhance encapsulation efficiency of C-Pc. Following its synthesis, LBG-g-poly(AAm-co-AAc) was thoroughly characterized using advanced techniques, like XRD, TGA, FTIR, NMR, and SEM, to analyze its structural and chemical properties. Moreover, the study examined the in-vitro C-Pc release profile from LBG-g-poly(AAm-co-AAc) based hydrogel (HgCPcLBG). Findings revealed that the maximum release of C-Pc (64.12 ± 2.69 %) was achieved at pH 7.4 over 48 h. Additionally, HgCPcLBG exhibited enhanced antioxidant performance and compatibility with blood. In vivo studies confirmed accelerated wound closure, and ELISA findings revealed reduced inflammatory markers (IL-6, IL-1ß, TNF-α) within treated skin tissue, suggesting a positive impact on injury repair. A low-cost and eco-friendly approach for creating LBG-g-poly(AAm-co-AAc) and HgCPcLBG has been developed. This method achieved sustained release of C-Pc, which could be a significant step forward in wound care technology.

Impact of Orthodontic Treatment on the Incidence of Dental Caries in Adolescents: A Prospective Cohort Study.

BACKGROUND: Orthodontic treatment is a widely embraced intervention aimed at enhancing dental aesthetics and correcting malocclusions among adolescents. However, concerns persist regarding its potential impact on oral health, particularly on the development of dental caries. This study aimed to systematically investigate the relationship between orthodontic treatment and the incidence of new carious lesions among adolescents. METHODS: A prospective cohort design involving adolescents aged 12-18 years was employed. A total of 82 patients met the inclusion criteria. In addition, an age-matched control group of 82 participants who did not undergo orthodontic treatment was included. The study included both a treatment group undergoing orthodontic treatment (braces or aligners) and an age-matched control group that did not undergo any orthodontic intervention. Demographic characteristics, orthodontic treatment details, and oral hygiene practices were documented at baseline and throughout the study period. Dental examinations at six-month intervals post-treatment were conducted to track the incidence and progression of carious lesions. RESULTS: The demographic characteristics, baseline oral health status, orthodontic treatment details, and oral hygiene practices were comparable between the treatment and control groups. Post-orthodontic treatment assessment revealed a slightly higher incidence of new carious lesions in the treatment group (14.6%) than in the control group (9.8%), although this difference was not statistically significant (p = 0.15). Dental examinations at six-month intervals demonstrated a gradual increase in caries incidence over time in both groups, with no substantial disparities observed. CONCLUSIONS: This study provides a comprehensive examination of the relationship between orthodontic treatment and the incidence of new carious lesions among adolescents. While a trend towards higher caries incidence in the treatment group was observed, the difference was not statistically significant. These findings contribute to the existing body of knowledge and emphasize the need for ongoing research to guide clinical practice.

Appraisal of folate functionalized bosutinib cubosomes against hepatic cancer cells: In-vitro, In-silico, and in-vivo pharmacokinetic study.

Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was -20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma.