Design and synthesis of novel 3,7-dihydro-1H-purine-2,6-diones as DPP-4 inhibitors: An in silico, in vitro and in vivo approach.

The inhibition of enzyme DPP-4 is pivotal for targeting type 2 diabetes mellitus (DM). The study introduces two series of novel 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones derivatives (PB01-PB10) and 3,7-dihydro-1H-purine-2,6-diones compounds (PB11-PB16) were developed using linagliptin scaffold. Sixteen derivatives were synthesized and screened in vitro against DPP-4, revealing IC ranging from 15.

Ultrashort Peptide Hydrogels Biomaterials with Potent Antibacterial Activity.

For the past few decades, ultrashort peptide hydrogels have been at the forefront of biomaterials due to their unique properties like biocompatibility, tunable mechanical properties, and potent antibacterial activity. These ultrashort peptides self-assemble into a hydrogel matrix with nanofibrous networks. In this minireview, we have explored the design and self-assembly of these ultrashort peptide hydrogels by focusing on their antibacterial properties.

The Opportunities and Challenges of Mesenchymal Stem Cells-Derived Exosomes in Theranostics and Regenerative Medicine.

Cell-secreted nanovesicles of endosomal origin, called exosomes, are vital for mediating intracellular communication. As local or distal transporters of intracellular cargo, they reflect the unique characteristics of secretory cells and establish cell-specific interactions via characteristic surface proteins and receptors. With the advent of rapid isolation, purification, and identification techniques, exosomes have become an attractive choice for disease diagnosis (exosomal content as biomarkers), cell-free therapy, and tissue regeneration.

Development of bioengineered 3D patient derived tumor organoid model focusing dynamic Fibroblast-Stem Cell reciprocity.

Three-dimensional (3D) models, such as tumor spheroids and organoids, are increasingly developed by integrating tissue engineering, regenerative medicine, and personalized therapy strategies. These advanced 3D in-vitro models are not merely endpoint-driven but also offer the flexibility to be customized or modulated according to specific disease parameters. Unlike traditional 2D monolayer cultures, which inadequately capture the complexities of solid tumors, 3D co-culture systems provide a more accurate representation of the tumor microenvironment.

Costus igneus: A Versatile Herbal Remedy for Multiple Health Conditions.

Costus igneus, commonly known as the insulin plant, is a potent medicinal herb with a wide range of pharmacological activities. Traditionally used in diabetes management, recent studies have highlighted its antidiabetic, antioxidant, antimicrobial, hepatoprotective, and kidney stone inhibitor properties. Phytochemical analyses reveal the presence of saponins, flavonoids, alkaloids, steroids, and terpenoids, which contribute to its therapeutic effects.

Biopharmaceutical and pharmacokinetic attributes to drive nanoformulations of small molecule tyrosine kinase inhibitors.

Buoyed by the discovery of small-molecule tyrosine kinase inhibitors (smTKIs), significant impact has been made in cancer chemotherapeutics. However, some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties. Almost all of these molecules exhibit significant inter- and intra-patient variations in plasma concentration-time profiles.

Challenges and Opportunities in Developing Tracheal Substitutes for the Recovery of Long-Segment Defects.

Tracheal resection and reconstruction procedures are necessary when stenosis, tracheomalacia, tumors, vascular lesions, or tracheal injury cause a tracheal blockage. Replacement with a tracheal substitute is often recommended when the trauma exceeds 50% of the total length of the trachea in adults and 30% in children. Recently, tissue engineering and other advanced techniques have shown promise in fabricating biocompatible tracheal substitutes with physical, morphological, biomechanical, and biological characteristics similar to native trachea.

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib.

Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.

Peptide-Based Biomaterials for Bone and Cartilage Regeneration.

The healing of osteochondral defects (OCDs) that result from injury, osteochondritis, or osteoarthritis and bear lesions in the cartilage and bone, pain, and loss of joint function in middle- and old-age individuals presents challenges to clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage separately; however, none of them addressed the simultaneous healing of these tissues in the complicated heterogeneous environment of the osteochondral (OC) interface.

Recent Advances and Challenges in the Early Diagnosis and Treatment of Preterm Labor.

Preterm birth (PTB) is the primary cause of neonatal mortality and long-term disabilities. The unknown mechanism behind PTB makes diagnosis difficult, yet early detection is necessary for controlling and averting related consequences. The primary focus of this work is to provide an overview of the known risk factors associated with preterm labor and the conventional and advanced procedures for early detection of PTB, including multi-omics and artificial intelligence/machine learning (AI/ML)- based approaches.

Cu(II)-Catalyzed Aminocyclization of -Propargyl Hydrazones to Substituted Pyrazolines.

An efficient route for the copper(II)-catalyzed synthesis of substituted pyrazolines from readily accessible -propargyl hydrazones has been reported under open flask conditions via intramolecular C-N bond formation. -acyl and -tosyl-substituted pyrazolines have been prepared in moderate to excellent yields. Mechanistic investigations using NMR, high-resolution mass spectrometry (HRMS), and Hammett analyses suggest that the Cu(II) catalyst generally acts as a Lewis acid to form an iminium-ion intermediate via cyclization, which afforded the desired pyrazolines upon hydrolysis.

Piezoelectric-based bioactive zinc oxide-cellulose acetate electrospun mats for efficient wound healing: an insight.

Being a complex physiological process involving the removal of damaged tissue debris and creating a new microenvironment for host tissue regeneration, wound healing is still a major challenge for healthcare professionals. Disruption of this process can lead to tissue inflammation, pathogenic infections, and scar formation. Current wound healing treatments primarily focus on passive tissue healing, lacking active engagement in the healing process.

Targeting Staphylococcal Cell-Wall Biosynthesis Protein FemX Through Steered Molecular Dynamics and Drug-Repurposing Approach.

-mediated infection is a serious threat in this antimicrobial-resistant world. has become a "superbug" by challenging conventional as well as modern treatment strategies. Nowadays, drug repurposing has become a new trend for the discovery of new drug molecules.

Metal-free synthesis of selenoesters directly from carboxylic acids using bifunctional selenoureas under batch and continuous-flow conditions.

A new metal-free method for the synthesis of selenoesters directly from carboxylic acids in a flow reactor is reported. The carboxylic acids, Michael acceptors, and bifunctional selenoureas (source of selenium and nucleophile, activator of carbonyl group) were reacted to obtain selenoesters (up to 70% yield). An evidence-backed plausible mechanism is also presented.

Recent Developments in the Design of New Water-Soluble Boron Dipyrromethenes and Their Applications: An Updated Review.

Boron-dipyrromethene (BODIPY) and its derivatives play an important role in the area of organic fluorophore chemistry. Recently, the water-soluble boron-dipyrromethene dyes have increasingly received interest. The structural modification of the BODIPY core by incorporating different neutral and ionic hydrophilic groups makes it water-soluble.

Patient-specific femoral implant design using metamaterials for improving load transfer at proximal-lateral region of the femur.

Loading configuration of hip joint creates resultant bending effect on femoral implants. So, the lateral side of femoral implant which is under tension retracts from peri‑implant bone due to positive Poisson's ratio. This retraction of implant leads to load shielding and gap opening in proximal-lateral region, thereby allowing entry of wear particle to implant-bone interface.

Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches.

The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin's stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach.

Expanding the Toolbox of Target Directed Bio-Orthogonal Synthesis: In Situ Direct Macrocyclization by DNA Templates.

Herein, we demonstrate for the first time that noncanonical DNA can direct macrocyclization-like challenging reactions to synthesize gene modulators. The planar G-quartets present in DNA G-quadruplexes (G4s) provide a size complementary reaction platform for the bio-orthogonal macrocyclization of bifunctional azide and alkyne fragments over oligo- and polymerization. G4s immobilized on gold-coated magnetic nanoparticles have been used as target templates to enable easy identification of a selective peptidomimetic macrocycle.

Simulation and experimental investigation of the surgical needle deflection model during the rotational and steady insertion process.

Needle insertion is executed in numerous medical and brachytherapy events. Exact needle insertion into inhomogeneous soft biological tissue is of useful importance due to its significance in clinical diagnosis (especially percutaneous) and treatments. The surgical needles used in such processes can deflect during the percutaneous process.

Peptide-Based Low Molecular Weight Photosensitive Supramolecular Gelators.

Over the last couple of decades, stimuli-responsive supramolecular gels comprising synthetic short peptides as building blocks have been explored for various biological and material applications. Though a wide range of stimuli has been tested depending on the structure of the peptides, light as a stimulus has attracted extensive attention due to its non-invasive, non-contaminant, and remotely controllable nature, precise spatial and temporal resolution, and wavelength tunability. The integration of molecular photo-switch and low-molecular-weight synthetic peptides may thus provide access to supramolecular self-assembled systems, notably supramolecular gels, which may be used to create dynamic, light-responsive "smart" materials with a variety of structures and functions.

Study of the surgical needle and biological soft tissue interaction phenomenon during insertion process for medical application: A Survey.

The insertion of the surgical needle in soft tissue has involved significant interest in the current time because of its purpose in minimally invasive surgery (MIS) and percutaneous events like biopsies, PCNL, and brachytherapy. This study represents a review of the existing condition of investigation on insertion of a surgical needle in biological living soft tissue material. As observes the issue from numerous phases, like, analysis of the cutting forces modeling (insertion), tissue material deformation, analysis of the needle deflection for the period of the needle insertion, and the robot-controlled insertion procedures.

An insight into SARS-CoV-2 structure, pathogenesis, target hunting for drug development and vaccine initiatives.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been confirmed to be a new coronavirus having 79% and 50% similarity with SARS-CoV and MERS-CoV, respectively. For a better understanding of the features of the new virus SARS-CoV-2, we have discussed a possible correlation between some unique features of the genome of SARS-CoV-2 in relation to pathogenesis. We have also reviewed structural druggable viral and host targets for possible clinical application if any, as cases of reinfection and compromised protection have been noticed due to the emergence of new variants with increased infectivity even after vaccination.