QbD-guided phospholipid-tagged nanonized boswellic acid naturosomal delivery for effective rheumatoid arthritis treatment.

Studies have reported the potential role of Boswellic acids (BAs), bioactive pentacyclic triterpenes from (BS), in treating rheumatoid arthritis (RA). However, poor water solubility and limited oral absorption are restricting factors for its better therapeutic efficacy. Based on these assumptions, the current study aimed to develop naturosomal delivery of BAs to boost their extremely low bioavailability, colloidal stability, and water solubility.

Integrated machine learning and physics-based methods assisted de novo design of Fatty Acyl-CoA synthase inhibitors.

Background: Tuberculosis is an infectious disease that has become endemic worldwide. The causative bacteria (Mtb) is targeted via several exciting drug targets. One newly discovered target is the Fatty Acyl-CoA synthase, which plays a significant role in activating the long-chain fatty acids.

The Mycobacterium tuberculosis Cell Wall: An Alluring Drug Target for Developing Newer Anti-TB Drugs-A Perspective.

The Mycobacterium cell wall is a capsule-like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti-TB drugs.

Structural insights into i-motif DNA structures in sequences from the insulin-linked polymorphic region.

The insulin-linked polymorphic region is a variable number of tandem repeats region of DNA in the promoter of the insulin gene that regulates transcription of insulin. This region is known to form the alternative DNA structures, i-motifs and G-quadruplexes. Individuals have different sequence variants of tandem repeats and although previous work investigated the effects of some variants on G-quadruplex formation, there is not a clear picture of the relationship between the sequence diversity, the DNA structures formed, and the functional effects on insulin gene expression.

Identification of mycobacterial Thymidylate kinase inhibitors: a comprehensive pharmacophore, machine learning, molecular docking, and molecular dynamics simulation studies.

Thymidylate kinase (TMK) is a pivotal enzyme in Mycobacterium tuberculosis (Mtb), crucial for phosphorylating thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), thereby playing a critical role in DNA biosynthesis. Dysregulation or inhibition of TMK activity disrupts DNA replication and cell division, making it an attractive target for anti-tuberculosis drug development. In this study, the statistically validated pharmacophore mode was developed from a set of known TMK inhibitors.

Identification and Design of Novel Potential Antimicrobial Peptides Targeting Mycobacterial Protein Kinase PknB.

Antimicrobial peptides have gradually gained advantages over small molecule inhibitors for their multifunctional effects, synthesising accessibility and target specificity. The current study aims to determine an antimicrobial peptide to inhibit PknB, a serine/threonine protein kinase (STPK), by binding efficiently at the helically oriented hinge region. A library of 5626 antimicrobial peptides from publicly available repositories has been prepared and categorised based on the length.

PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.

In the realm of oncology, the transformative impact of PROTAC (PROteolysis TAgeting Chimeras) technology has been particularly pronounced since its introduction in the 21st century. Initially conceived for cancer treatment, PROTACs have evolved beyond their primary scope, attracting increasing interest in addressing a diverse array of medical conditions. This expanded focus includes not only oncological disorders but also viral infections, bacterial ailments, immune dysregulation, neurodegenerative conditions, and metabolic disorders.

Quest for Anti-SARS-CoV-2 antiviral therapeutics: in-silico and in-vitro analysis of edible mushroom- Cordyceps militaris.

Background: The emergence and evolution of SARS-CoV-2 resulted a severe threat to public health globally. Due to the lack of an effective vaccine with durable immunity, the disease transited into the endemic phase, necessitating potent antiviral therapy including a scientific basis for current traditional herbal medicine.

Objective: This study aimed to conduct a pharmacoinformatic analysis of selected chemical ingredients and in-vitro evaluation of Cordyceps militaris extract against SARS-CoV-2.

Identification of novel hit molecules targeting M. tuberculosis polyketide synthase 13 by combining generative AI and physics-based methods.

In this work we investigated the Pks13-TE domain, which plays a critical role in the viability of the mycobacteria. In this report, we have used a series of AI and Physics-based tools to identify Pks13-TE inhibitors. The Reinvent 4, pKCSM, KDeep, and SwissADME are AI-ML-based tools.

In Vitro Comparison to Evaluate Metal Ion Release: Nickel-Titanium vs. Titanium-Molybdenum Orthodontic Archwires.

Background When metals used in orthodontic materials are exposed to the oral environment, teeth, and gingivae over an extended period of time, they may gradually deteriorate. As a result, the patient is exposed to higher concentrations of metals and metal ions than what they would be exposed to through food and other sources. The goal of the current in vitro experiment was to evaluate and contrast the metal ion release from orthodontic archwires made of titanium-molybdenum alloy (TMA) and nickel-titanium (NiTi).

Identification of Mycobacterium tuberculosis transcriptional repressor EthR inhibitors: Shape-based search and machine learning studies.

Tuberculosis has been a challenge to the world since prehistoric times, and with the advent of drug-resistant strains, it has become more challenging to treat this infection. Ethionamide (ETH), a second-line drug, acts as a prodrug and targets mycolic acid synthesis by targeting the enoyl-acyl carrier protein reductase (InhA) enzyme. (Mtb) EthR is an ethA gene repressor required to activate prodrug ETH.

Machine learning assisted methods for the identification of low toxicity inhibitors of Enoyl-Acyl Carrier Protein Reductase (InhA).

Tuberculosis (TB) is one of the life-threatening infectious diseases with prehistoric origins and occurs in almost all habitable parts of the world. TB mainly affects the lungs, and its etiological agent is Mycobacterium tuberculosis (Mtb). In 2022, more than 10 million people were infected worldwide, and 1.

Current biomarkers and treatment strategies in Alzheimer disease: An overview and future perspectives.

Alzheimer's disease (AD), a progressive degenerative disorder first identified by Alois Alzheimer in 1907, poses a significant public health challenge. Despite its prevalence and impact, there is currently no definitive ante mortem diagnosis for AD pathogenesis. By 2050, the United States may face a staggering 13.

Nutritional Composition, Mineral Profiling, In Vitro Antioxidant, Antibacterial and Enzyme Inhibitory Properties of Selected Indian Guava Cultivars Leaf Extract.

L. is a small evergreen tree known for its magnificent medicinal and nutritional value. This study aimed to evaluate the nutritional profile and in vitro pharmacological potentialities of the different leaf extracts of four cultivars of namely Surka chitti, Allahabad safeda, Karela, and Lucknow-49.

A Review on Five and Six-Membered Heterocyclic Compounds Targeting the Penicillin-Binding Protein 2 (PBP2A) of Methicillin-Resistant (MRSA).

is a common human pathogen. Methicillin-resistant (MRSA) infections pose significant and challenging therapeutic difficulties. MRSA often acquires the non-native gene PBP2a, which results in reduced susceptibility to β-lactam antibiotics, thus conferring resistance.

Rutin from Begonia roxburghii modulates iNOS and Sep A activity in treatment of Shigella flexneri induced diarrhoea in rats: An in vitro, in vivo and computational analysis.

In developing countries, diarrhoea is a major issue of concern, where consistent use of antibiotics has resulted in several side effects along with development of resistance among pathogens against these antibiotics. Since natural products are becoming the treatment of choice, therefore present investigation involves mechanistic evaluation of antidiarrhoeal potential of Begonia roxburghii and its marker rutin against Shigella flexneri (SF) induced diarrhoea in rats following in vitro, in vivo and in silico protocols. The roots of the plant are used as vegetable in the North East India and are also used traditionally in treating diarrhoea.

Isolation and Characterization of Anti-Inflammatory Compounds from L.f. Stem Bark.

The anti-inflammatory effect of the ethyl acetate extract of bark (EAFMB) was investigated in acute and chronic (21 days) inflammation induced in Wistar albino rats. EAFMB (200 mg/kg b.w.

Process Optimization for the Bioinspired Synthesis of Gold Nanoparticles Using , Its Characterization, and Assessment of Enhanced Therapeutic Efficacy.

The promising therapeutic implications of nanoparticles have spurred their development for biomedical applications. An eco-friendly methodology synthesizes gold nanoparticles using , an edible mushroom (-Au-NPs), using a quality-by-design approach (central composite design). UV-visible spectroscopy analysis revealed an absorption peak at 540-550 nm, thus confirming the synthesis of gold nanoparticles.

Analysing the impact of eriosematin E from Vogel. against different diarrhoeagenic pathovars of using and approach.

Since diarrhoea is reportedly the third largest cause of fatality among kids, therefore it is considered to be one of the major areas of concerns among developing nations. The main causative agents of diarrhoea include , and where shares the maximum contribution. The roots of the plant Vogel.

Unlocking the potential of PROTACs: A comprehensive review of protein degradation strategies in disease therapy.

The technology known asPROTACs (PROteolysisTArgeting Chimeras) is a method of protein degradation. Utilising bifunctional small molecules, the ubiquitin-proteosome system (UPS) is used to induce the ubiquitination and degradation of target proteins. In addition to being novel chemical knockdown agents for biological studies that are catalytic, reversible, and rapid, PROTACs used in the treatment for disorders like cancer, immunological disorders, viral diseases, and neurological disorders.

TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair.

Environmental agents like ionizing radiation (IR) and chemotherapeutic drugs can cause severe damage to the DNA, often in the form of double-strand breaks (DSBs). Remaining unrepaired, DSBs can lead to chromosomal rearrangements, and cell death. One major error-free pathway to repair DSBs is homologous recombination repair (HRR).

Fabrication of chitosan nanocomposites loaded with biosynthetic metallic nanoparticles and their therapeutic investigation.

The present research demonstrates the formation of zinc oxide nanoparticles facilitated by Cissus quadrangularis (CQ-ZnONPs) and subsequent synthesis of chitosan-conjugated nanocomposites (CQ-CS/ZnONCs) along with their biological assessment. The biosynthesized nanoparticles and nanocomposites were physicochemically characterized and therapeutically assessed for their antioxidant, antibacterial, and antidiabetic potential. The formation of CQ-ZnONPs and CQ-CS/ZnONCs was preliminarily validated by the change in color and subsequently by UV-visible spectroscopic analysis.

Effective Drug Candidates against Global Pandemic of Novel Corona Virus (nCoV-2019): A Probability Check through Computational Approach for Public Health Emergency.

The infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started form Wuhan, Chinais a devastating and the incidence rate has increased worldwide. Due to the lack of effective treatment against SARS-CoV-2, various strategies are being tested in China and throughout the world, including drug repurposing. To identify the potent clinical antiretroviral drug candidate against pandemic nCov-19 through computational tools.