Development and evaluation of Amikacin-loaded carbopol hydrogel for topical treatment of Mycobacterium marinum skin infections.

Mycobacterium marinum is a slow growing Non-Tuberculosis Mycobacteria (NTM) known to cause skin and subcutaneous tissue infections known as "fish tank granuloma" in humans. Treatment of M. marinum skin infections can last for several months or even years.

Paired single-B-cell transcriptomics and receptor sequencing reveal activation states and clonal signatures that characterize B cells in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained.

Identification of a Staphylococcus aureus amidase catalytic domain inhibitor to prevent biofilm formation by sequential virtual screening, molecular dynamics simulation and biological evaluation.

Staphylococcus aureus (S. aureus) is one of the common causes of implant associated biofilm infections and their biofilms are resistant to antibiotics. S.

Identification of a PD1/PD-L1 inhibitor by structure-based pharmacophore modelling, virtual screening, molecular docking and biological evaluation.

PD-1/PD-L1 is a critical druggable target for immunotherapy against sepsis. Chemoinformatics techniques involved the structure-based 3D pharmacophore model development followed by virtual screening of small molecule databases to identify the small molecules against PD-L1 pathway inhibition. Raltitrexed and Safinamide act as potent repurposed drugs, and three other Specs database compounds using in silico methods.

A multicenter study of ICU resource utilization in pediatric, adolescent and young adult patients post CAR-T therapy.

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging.

A phytochemical-based medication search for the SARS-CoV-2 infection by molecular docking models towards spike glycoproteins and main proteases.

Identifying best bioactive phytochemicals from different medicinal plants using molecular docking techniques demonstrates a potential pre-clinical compound discovery against SARS-CoV-2 viral infection. The screening of bioactive phytochemicals with the two druggable targets of SARS-CoV-2 by simple precision/extra precision molecular docking methods was used to compute binding affinity at its active sites. phyllaemblicin and cinnamtannin class of phytocompounds showed a better binding affinity range (-9.

Cytokine Release Syndrome and Associated Acute Toxicities in Pediatric Patients Undergoing Immune Effector Cell Therapy or Hematopoietic Cell Transplantation.

Immune effector cells (IEC) are a powerful and increasingly targeted tool, particularly for the control and eradication of malignant diseases. However, the infusion, expansion, and persistence of autologous or allogeneic IEC or engagement of endogenous immune cells can be associated with significant systemic multi-organ toxicities. Here we review the signs and symptoms, grading and pathophysiology of immune-related toxicities arising in the context of pediatric immunotherapies and haploidentical T cell replete Hematopoietic Cell Transplantation (HCT).

Doxycycline prevents blood-brain barrier dysfunction and microvascular hyperpermeability after traumatic brain injury.

The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary injuries following traumatic brain injury (TBI). Microvascular hyperpermeability and cerebral edema resulting from BBB dysfunction after TBI leads to elevation of intracranial pressure, secondary brain ischemia, herniation, and brain death. There are currently no effective therapies to modulate the underlying pathophysiology responsible for TBI-induced BBB dysfunction and hyperpermeability.

Discovery of Anticancer Hybrid Molecules by Supervised Machine Learning Models and Validation in Drug Resistant Chronic Myeloid Leukemia Cells.

The concept of hybrid drugs for targeting multiple aberrant pathways of cancer, by combining the key pharmacophores of clinically approved single-targeted drugs, has emerged as a promising approach for overcoming drug-resistance. Here, we report the design of unique hybrid molecules by combining the two pharmacophores of clinically approved BCR-ABL inhibitor (ponatinib) and HDAC inhibitor (vorinostat) and results of studies in drug-resistant CML cells. Robust 2D-QSAR and 3D-pharmacophore machine learning supervised models were developed for virtual screening of the hybrid molecules based on their predicted BCR-ABL and HDAC inhibitory activity.

Machine learning models for predicting the activity of AChE and BACE1 dual inhibitors for the treatment of Alzheimer's disease.

Multi-target directed ligand-based 2D-QSAR models were developed using different N-benzyl piperidine derivatives showing inhibitory activity toward acetylcholinesterase (AChE) and β-Site amyloid precursor protein cleaving enzyme (BACE1). Five different classes of molecular descriptors belonging to spatial, structural, thermodynamics, electro-topological and E-state indices were used for machine learning by linear method, genetic function approximation (GFA) and nonlinear method, support vector machine (SVM) and artificial neural network (ANN). Dataset used for QSAR model development includes 57 AChE and 53 BACE1 inhibitors.

Predicting the Molecular Mechanism of EGFR Domain II Dimer Binding Interface by Machine Learning to Identify Potent Small Molecule Inhibitor for Treatment of Cancer.

Epidermal growth factor receptor (EGFR) is a transmembrane druggable target controlling cellular differentiation, proliferation, migration, survival and invasion. EGFR activation mainly occurs by its homo/hetro dimerization molecular phenomenon leading to tumor development and invasion. Several tyrosine kinase based inhibitors were discovered as potent anti-cancer drugs.

Multiple e-Pharmacophore modeling to identify a single molecule that could target both streptomycin and paromomycin binding sites for 30S ribosomal subunit inhibition.

The bacterial ribosome is an established target for anti-bacterial therapy since decades. Several inhibitors have already been developed targeting both defined subunits (50S and 30S) of the ribosome. Aminoglycosides and tetracyclines are two classes of antibiotics that bind to the 30S ribosomal subunit.

Computational simulations and experimental validation of structure- physicochemical properties of pristine and functionalized graphene: Implications for adverse effects on p53 mediated DNA damage response.

Recent reports indicated DNA damaging potential of few-layer graphene in human cell systems. Here, we used computational technique to understand the interaction of both pristine (pG) or carboxyl functionalized graphene (fG) of different sizes (1, 6, and 10nm) with an important DNA repair protein p53. The molecular docking study revealed strong interaction between pG and DNA binding domains (DBD) of p53 with binding free energies (BE) varying from -12.

Mechanistic understanding of Phenyllactic acid mediated inhibition of quorum sensing and biofilm development in Pseudomonas aeruginosa.

Pseudomonas aeruginosa depends on its quorum sensing (QS) system for its virulence factors' production and biofilm formation. Biofilms of P. aeruginosa on the surface of indwelling catheters are often resistant to antibiotic therapy.

Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques.

Antimicrobial activities of secondary metabolites and phylogenetic study of sponge endosymbiotic bacteria, sp. at Agatti Island, Lakshadweep Archipelago.

Twenty-one species of sponges were recorded under the class of Demospongiae and Calcareous sponges of which 19 species were new to Agatti reef. A total of 113 Sponge endosymbiotic bacterial strains were isolated from twenty-one species of sponges and screened for antimicrobial activity. Five bacterial strains of sponge endosymbiotic bacteria (SEB) namely SEB32, SEB33, SEB36, SEB43 and SEB51 showed antimicrobial activity against virulent marine fish pathogens such as , , , , sp.

Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice.

In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge.

Understanding the Structure-Function Relationship of Lysozyme Resistance in Staphylococcus aureus by Peptidoglycan O-Acetylation Using Molecular Docking, Dynamics, and Lysis Assay.

Lysozyme is an important component of the host innate defense system. It cleaves the β-1,4 glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine of bacterial peptidoglycan and induce bacterial lysis. Staphylococcus aureus (S.

Less is more: Ebola virus surface glycoprotein expression levels regulate virus production and infectivity.

Unlabelled: The Ebola virus (EBOV) surface glycoprotein (GP1,2) mediates host cell attachment and fusion and is the primary target for host neutralizing antibodies. Expression of GP1,2 at high levels disrupts normal cell physiology, and EBOV uses an RNA-editing mechanism to regulate expression of the GP gene. In this study, we demonstrate that high levels of GP1,2 expression impair production and release of EBOV virus-like particles (VLPs) as well as infectivity of GP1,2-pseudotyped viruses.

Dual binding site and selective acetylcholinesterase inhibitors derived from integrated pharmacophore models and sequential virtual screening.

In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer's randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.

Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents.

A novel series of pyrazole derivatives were synthesized and evaluated in vivo for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Among all compounds, 5a, and 5b showed comparable anti-inflammatory activity to Nimesulide, the standard drug taken for the studies. In silico (docking) studies were carried out to investigate the theoretical binding mode of the compounds to target the cyclooxygenase (COX-2) using Autodock 4.

Chemical modifications of cinchona alkaloids lead to enhanced inhibition of human butyrylcholinesterase.

Butyrylcholinesterase (BChE) inhibitors were identified from a collection containing cinchonine, cinchonidine and synthetic derivatives, and further characterized using cytotoxicity and molecular docking studies. The most active ones were: (10 triple bond)-10,11-dibromo-10,11-dihydrocinchonidine (11), a competitive inhibitor with Ki = 3.45 +/- 0.