Design, synthesis and evaluation of new thiazolidin-4-ones as LPA receptor antagonists for breast cancer therapy.

Breast cancer has been a leading cause of mortality among women worldwide in recent years. Targeting the lysophosphatidic acid (LPA)-LPA pathway using small molecules could improve breast cancer therapy. Thiazolidin-4-ones were developed and tested on MCF-7 cancer cells, and active compounds were analyzed for their effects on apoptosis, migration angiogenesis and LPA protein and gene expression.

Novel Antitubercular Agents: Design, Synthesis, Molecular Dynamic and Biological Studies of Pyrazole - 1,2,4-Triazole Conjugates.

Mycobacterium tuberculosis (Mtb) has numerous cell wall and non-cell wall mediated receptors for drug action, of which cell wall mediated targets were found to be more promising because of their pivotal role in bacterial protection and survival. Herein, we reported the design and synthesis of a series of pyrazole-linked triazoles based on the reported structural features of promising drug candidates that target DprE1 receptors through a Structure-based drug design (SBDD) approach (6a-6j and 7a-7j). The synthesized compounds were evaluated for their in-vitro antitubercular activity against virulent strains of Mtb H37Rv.

Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy.

Functional inactivation of wild-type p53 is a major trait of cancerous cells. In many cases, such inactivation occurs by either gene mutations or due to overexpression of p53 binding partners. This review focuses on an overexpressed p53 binding partner called mortalin, a mitochondrial heat shock protein that sequesters both wild-type and mutant p53 in malignant cells due to changes in subcellular localization.

Machine learning and deep learning in data-driven decision making of drug discovery and challenges in high-quality data acquisition in the pharmaceutical industry.

Predicting novel small molecule bioactivities for the target deconvolution, hit-to-lead optimization in drug discovery research, requires molecular representation. Previous reports have demonstrated that machine learning (ML) and deep learning (DL) have substantial implications in virtual screening, peptide synthesis, drug ADMET screening and biomarker discovery. These strategies can increase the positive outcomes in the drug discovery process without false-positive rates and can be achieved in a cost-effective way with a minimum duration of time by high-quality data acquisition.

Isolation and characterization of ACE-I inhibitory peptides from ribbonfish for a potential inhibitor of the main protease of SARS-CoV-2: An in silico analysis.

Recently, multifunctional fish peptides (FWPs) have gained a lot of attention because of their different biological activities. In the present study, three angiotensin-I converting enzyme (ACE-I) inhibitory peptides [Ala-Pro-Asp-Gly (APDG), Pro-Thr-Arg (PTR), and Ala-Asp (AD)] were isolated and characterized from ribbonfish protein hydrolysate (RFPH) and described their mechanism of action on ACE activity. As per the results, peptide PTR showed ≈ 2 and 2.

Lysophosphatidic acid (LPA) receptor modulators: Structural features and recent development.

Lysophosphatidic acid (LPA) activates six LPA receptors (LPAR) and regulates various cellular activities such as cell proliferation, cytoprotection, and wound healing. Many studies elucidated the pathological outcomes of LPA are due to the alteration in signaling pathways, which include migration and invasion of cancer cells, fibrosis, atherosclerosis, and inflammation. Current pathophysiological research on LPA and its receptors provides a means that LPA receptors are new therapeutic targets for disorders associated with LPA.

Aachen-Heerlen annotated steel microstructure dataset.

Studying steel microstructures yields important insights regarding its mechanical characteristics. Within steel, microstructures transform based on a multitude of factors including chemical composition, transformation temperatures, and cooling rates. Martensite-austenite (MA) islands in bainitic steel appear as blocky structures with abstract shapes that are difficult to identify and differentiate from other types of microstructures.

Dengue structural proteins as antiviral drug targets: Current status in the drug discovery & development.

Dengue virus belongs to the class of RNA viruses and subclass of enveloped single-stranded positive-sense RNA virus. It causes dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS), where DHF and DSS are life-threatening. Even though dengue is an age-old disease, it is still a mystery and continues to be a global threat.

Sonographic pattern of median nerve enlargement in Hansen's neuropathy.

Objectives: Median nerve enlargement in leprosy seems to be more proximal than in carpal tunnel syndrome (CTS), but this feature has not been studied systematically. The aim of the study was to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS.

Materials And Methods: Transverse sections of the median nerve were recorded from wrist to the mid-forearm (at distal wrist crease and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) in patients with leprosy, CTS and healthy subjects using high-resolution ultrasound.

Nanoparticle surface energy transfer (NSET) in ferroelectric liquid crystal-metallic-silver nanoparticle composites: Effect of dopant concentration on NSET parameters.

In the recent past, the resonance energy transfer studies using metallic nanoparticles has become a matter of quintessence in modern technology, which considerably extends its applications in probing specific biological and chemical processes. In the present study, metallic-silver nanoparticles of 2-4 nm (diameter) capped with hexanethiol ligand are developed and dispersed in ferroelectric liquid crystal (FLC). The morphology of nanoparticles was characterized using HR-TEM and SEM techniques.

A rare cause of median neuropathy at the carpal tunnel: Thrombosis of the persistent median artery.

Carpal tunnel syndrome is a common peripheral nerve entrapment neuropathy caused due to compression of the median nerve at the level of the wrist joint. Bifid median nerve associated with a persistent median artery is a rare entity and in itself asymptomatic anatomical variant. However, distension of the persistent median artery due to a thrombus can be symptomatic due to compression on the median nerve and can compromise the blood flow to the palm.

Hevea brasiliensis mediated synthesis of nanocellulose: Effect of preparation methods on morphology and properties.

In present research, Hevea brasiliensis (Rubber Wood) converted into cellulose by pre-treatment with NaOH (5%) and NaClO (5%). In addition, the cellulose was converted to nanocellulose (NC) using ionic liquid, acid hydrolysis and TEMPO oxidation accompanied by ultra-sonication. The prepared nanocellulose characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Fourier transformation infrared spectroscopy (FT-IR).

Comprehensive study of interaction between biocompatible PEG-InP/ZnS QDs and bovine serum albumin.

Polyethylene glycol (PEG) surface modified biocompatible InP/ZnS quantum dots (QDs) act as a potential alternative for conventional carcinogenic cadmium-based quantum dots for in vivo and in vitro studies. Comprehensively, we studied the interaction between a model protein bovine serum albumin (BSA) and PEGylated toxic free InP/ZnS QDs using various spectroscopic tools such as absorption, fluorescence quenching, time resolved and synchronous fluorescence spectroscopic measurements. These studies principally show that tryptophan (Trp) residues of BSA have preferable binding affinity towards PEG-InP/ZnS QDs surface and a blue shift in Trp fluorescence emission is a signature of conformational changes in its hydrophobic microenvironment.

Recent Advances and Structural Features of Enoyl-ACP Reductase Inhibitors of Mycobacterium tuberculosis.

Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase.

Carpal tunnel syndrome: Analyzing efficacy and utility of clinical tests and various diagnostic modalities.

Background: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, but not adequately studied in India.

Objectives: To study clinical tests, nerve conduction studies (NCS), ultrasonography (USG), and magnetic resonance imaging (MRI) in diagnosing CTS.

Materials And Methods: We diagnosed CTS in 54 patients (93 hands) out of 60 screened patients with symptoms compatible with CTS, including 19 control patients (23 hands).

Design, Synthesis and Optoelectronic Properties of Unsymmetrical Oxadiazole Based Indene Substituted Derivatives as Deep Blue Fluoroscent Materials.

A series of novel unsymmetrically substituted indene-oxadiazole derivatives (3a-f) have been designed and synthesized by employing palladium catalysed Suzuki cross coupling reaction in high yields. The structural integrity of all the novel compounds was established by (1)H, (13)C NMR and LC/MS analysis. These compounds are amorphous in nature and are remarkably stable to long term storage under ambient conditions.

Structural insights of PA-824 derivatives: ligand-based 3D-QSAR study and design of novel PA824 derivatives as anti-tubercular agents.

With the purpose of designing novel chemical entities with improved inhibitory potencies against drug-resistant Mycobacterium tuberculosis, the 3D- quantitative structure-activity relationship (QSAR) studies were carried out on biphenyl analogs of the tuberculosis (TB) drug, PA-824. Anti-mycobacterial activity (MABA) was considered for the 3D-QSAR studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. The best CoMFA and CoMSIA models were found statistically significant with cross-validated coefficients (q(2)) of 0.

Recurrent tumefactive demyelination: An unusual presentation.

Tumefactive multiple sclerosis (MS) is a rare variant of MS characterized by the presence of large demyelinating plaques of more than 2 cm, identified with magnetic resonance imaging (MRI). Distinguishing tumefactive lesions from other etiologies of intracranial space occupying lesions is necessary to avoid the inadvertent intervention. We had a 14-year-old girl who presented to us with two episodes of subacute hemiparesis over a span of 6 months.

A study of Guillain-Barré syndrome with reference to cranial neuropathy and its prognostic implication.

Background: Focused studies on cranial neuropathy in Guillain-Barré syndrome (GBS) and its prognostic implication are not done previously.

Aim: To study the clinical profile of GBS patients with special reference to cranial neuropathy and its prognostic implication.

Materials And Methods: The study included 61 patients with GB syndrome, fulfilling Asbury Cornblath's criteria for GB syndrome.

Response to abdominal hysterectomy with bilateral salpingo-oophorectomy in postmenopausal woman with anti-yo antibody mediated paraneoplastic cerebellar degeneration.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. PCD often precedes the cancer diagnosis by months to years. Here, we report a case of 44-year old postmenopausal woman who presented with PCD symptoms and high levels of anti-Yo antibodies titer since 8 months.

Design, synthesis and 3D-QSAR studies of new diphenylamine containing 1,2,4-triazoles as potential antitubercular agents.

A new series of new diphenylamine containing 1,2,4-triazoles were synthesized from 4-arylideneamino-5-[2-(2,6-dichlorophenylamino) benzyl]-2H-1,2,4-triazole-3(4H)-thiones 3a-f. The synthesized compounds were screened for in-vitro antimycobacterial and antibacterial activities. The synthesized compounds 4a, 4e and 4d have shown potential activity against Mycobacterium tuberculosis H37Rv strain with MIC of 0.

Guillain-Barre syndrome with posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity commonly associated with eclampsia, septicemia, chemotherapeutic drugs etc. Concurrent occurrence of Guillain-Barre syndrome (GBS) with PRES is a rare entity. Dysautonomia is a proposed mechanism for such occurrence.