Synthesis and potential anti-inflammatory response of indole and amide derivatives of ursolic acid in LPS-induced RAW 264.7 cells and systemic inflammation mice model: Insights into iNOS, COX2 and NF-κB.

Ursolic acid (3-hydroxy-urs-12-ene-28-oic acid, UA) is a pentacyclic triterpene present in numerous plants, fruits and herbs and exhibits various pharmacological effects. However, UA has limited clinical applicability since it is classified as BCS class IV molecule, characterized by low solubility, low oral bioavailability and low permeability. In the present study, UA was isolated from the biomass marc of Lavandula angustifolia and was structurally modified by an induction of indole ring at the C-3 position and amide group at the C-17 position with the aim to enhance its pharmacological potential.

Anti-inflammatory and anti-arthritic potential of methotrexate in combination with BA-25, an amino analogue of β-boswellic acid in the treatment of rheumatoid arthritis.

β- boswellic acid, a pentacyclic triterpene derived from Boswellia serrata is extensively known for its anti-inflammatory potential. BA-25 (3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene) is an amino analogue of β-boswellic acid that has shown anti-inflammatory potential in LPS-induced macrophages and animal models. The present study aims at investigation of the combination of BA-25 with the conventional gold standard DMARD methotrexate (MTX) for its anti-inflammatory and anti-arthritic potential using in vitro and in vivo experimental models.

Semisynthesis of Novel Dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione Natural Product Hybrids of Parthenin Followed by Their Cytotoxicity Evaluation.

Natural products possess unique and broader intricacies in the chemical space and have been essential for drug discovery. The crucial factor for drug discovery success is not the size of the library but rather its structural diversity. Although reports on the number of new structurally diverse natural products (NPs) have declined recently, researchers follow the next logical step: synthesizing natural product hybrids and their analogues using the most potent tool, diversity-oriented synthesis (DOS).

Gold nanoblackbodies-based multifunctional nanocomposite for multimodal cancer therapy.

Multifunctional nanocomposites are of potential use to achieve complete tumor elimination and, thus, to avoid tumor recurrence. Herein, polydopamine (PDA)-based gold nanoblackbodies (AuNBs) loaded with indocyanine green (ICG) and Doxorubicin (DOX) termed as A-P-I-D nanocomposite were investigated for multimodal plasmonic photothermal-photodynamic-chemotherapy. Upon near-infrared (NIR) irradiation, A-P-I-D nanocomposite showed enhanced photothermal conversion efficiency of 69.

In vitro and in vivo anticancer potential and molecular targets of the new colchicine analog IIIM-067.

Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells.

Methods: Sulforhodamine B (SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide (IIIM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4',6-diamidino-2-phenylindole (DAPI) and annexin V/propidium iodide.

Gold nanoblackbodies mediated plasmonic photothermal cancer therapy for melanoma.

Gold nanoblackbodies (AuNBs)-mediated plasmonic photothermal cancer therapy was investigated through melanoma-bearing mice. Polydopamine-coated Au nanoclusters were synthesized, termed AuNBs and PEGylated AuNBs (AuNBs-PEG). The photothermal response of AuNBs-PEG was evaluated upon low-intensity broadband near-infrared irradiation (785/62 nm; 0.

'Stenting the Lacrimal System in Modified Denker's for Mucormycosis: Really Needed!'-A Longitudinal Study.

Introduction: Recent advances in endoscopic paraphernalia have brought the once intricate anterior lateral wall of maxilla, within reach of the endoscopic surgeon. Endoscopic modified Denker's approach provides another route to reach the indiscernible sites of maxillary & other paranasal sinuses along with PPF (pterygo-palatine fossa)/ITF (infra-temporal fossa) region. This approach has been widely used Pan-India during the Post-Covid Mucormycosis Epidemic, in our country.

Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma.

Purpose: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC).

Patients And Methods: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status.

Synthetic Triterpenoid RTA-408: Limits Radiation Damage to Normal Tissue.

Objectives/hypothesis: To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model.

Study Design: Randomized, prospective study using an in vivo rat model.

Methods: Experimental animal study utilizing Sprague-Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA-408 (therapeutic drug); and 3) no radiation + DMSO.

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy.

Background/aims: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM.

Real time detection and quantification of Epstein Barr virus in different grades of oral gingivitis and periodontitis patients.

Background: Periodontal diseases are of microbial etiology and are globally causing loss of teeth in adult population. Many severe oral diseases have been recently associated to Herpes viruses, of which Epstein Barr Virus (EBV) and human cytomegalovirus (HCMV) have been indicated in the etiology of periodontal diseases.

Aim: The purpose of the study was to compare the effect of EBV in different types of periodontal diseases namely acute gingivitis, chronic gingivitis, acute and chronic, localized and generalized aggressive (juvenile) periodontitis and apical periodontitis.

Expression levels of A disintegrin and metalloproteases (ADAMs), and Th17-related cytokines and their association with Helicobacter pylori infection in patients with gastroduodenal diseases.

Expression levels of A disintegrin and metalloproteases (ADAMs) (10 and 17) and Th17-related cytokines [interleukin (IL) 17A, IL-17F, IL-33, IL-23, IL-23R] were investigated by quantitative real time polymerase chain reaction in gastric biopsies of patients with different gastroduodenal pathologies in the presence and absence of Helicobacter pylori infection. Patients with gastric cancer (GC) (n = 70, intestinal-type 38 and diffuse type 32), peptic ulcer disease [n = 50, duodenal ulcer (DU) 16 and gastric ulcer (GU) 34] and functional dyspepsia (n = 120) were included in the study. Further, the expression levels of ADAMs and Th17 cytokines were correlated with H.

Proteasome biology and therapeutics in cardiac diseases.

The ubiquitin proteasome system (UPS) is the major pathway for intracellular protein degradation in most organs, including the heart. UPS controls many fundamental biological processes such as cell cycle, cell division, immune responses, antigen presentation, apoptosis, and cell signaling. The UPS not only degrades substrates but also regulates activity of gene transcription at the post-transcription level.

The Role of Allograft Inflammatory Factor-1 in the Effects of Experimental Diabetes on B Cell Functions in the Heart.

Diabetes mellitus (DM) often causes chronic inflammation, hypertrophy, apoptosis and fibrosis in the heart and subsequently leads to myocardial remodeling, deteriorated cardiac function and heart failure. However, the etiology of the cardiac disease is unknown. Therefore, we assessed the gene expression in the left ventricle of diabetic and non-diabetic mice using Affymetrix microarray analysis.

High Fat Diet Upregulates Fatty Acid Oxidation and Ketogenesis via Intervention of PPAR-γ.

Background/aims: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis.

Methods: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy.

Epstein-Barr Virus Nuclear Antigen 3C Facilitates Cell Proliferation by Regulating Cyclin D2.

Cell cycle regulation is one of the hallmarks of virus-mediated oncogenesis. Epstein-Barr virus (EBV)-induced lymphomas express a repertoire of essential viral latent proteins that regulate expression of cell cycle-related proteins to dysregulate this process, thereby facilitating the proliferation of infected cells. We now demonstrate that the essential EBV latent protein 3C (EBNA3C) stabilizes cyclin D2 to regulate cell cycle progression.

Molecular network, pathway, and functional analysis of time-dependent gene changes related to cathepsin G exposure in neonatal rat cardiomyocytes.

The molecular pathways activated in response to acute cathepsin G (CG) exposure, as well as the mechanisms involved in activation of signaling pathways that culminate in myocyte detachment and apoptosis remain unclear. This study aimed to determine the changes in gene expression patterns associated with time dependent CG exposure to neonatal rat cardiomyocytes (NRCMs). Microarray analysis revealed a total of 451, 572 and 1127 differentially expressed genes after CG exposure at 1, 4 and 8 h respectively.

Epigenetic Regulation of Tumor Suppressors by Enhances EBV-Induced Proliferation of Gastric Epithelial Cells.

and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells.

HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk.

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined.

An EBV recombinant deleted for residues 130-159 in EBNA3C can deregulate p53/Mdm2 and Cyclin D1/CDK6 which results in apoptosis and reduced cell proliferation.

Epstein-Barr virus (EBV), a gamma herpes virus is associated with B-cell malignancies. EBNA-3C is critical for in vitro primary B-cell transformation. Interestingly, the N terminal domain of EBNA3C which contains residues 130-159, interacts with various cellular proteins, such as p53, Mdm2, CyclinD1/Cdk6 complex, and E2F1.

Gammaherpesvirus Infection of Human Neuronal Cells.

Unlabelled: Gammaherpesviruses human herpesvirus 4 (HHV4) and HHV8 are two prominent members of the herpesvirus family associated with a number of human cancers. HHV4, also known as Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus prevalent in 90 to 95% of the human population, is clinically associated with various neurological diseases such as primary central nervous system lymphoma, multiple sclerosis, Alzheimer's disease, cerebellar ataxia, and encephalitis. However, the possibility that EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) can directly infect neurons has been largely overlooked.

Dissecting the contribution of EBNA3C domains important for EBV-induced B-cell growth and proliferation.

Epstein-Barr virus (EBV) is an oncogenic gammaherpes virus which is linked to pathogenesis of several human lymphatic malignancies. The EBV essential latent antigen EBNA3C is critical for efficient conversion of primary human B-lymphocytes to lymphoblastic cell lines and for continued LCL growth. EBNA3C, an EBV latent antigen with oncogenic potential can bind and regulate the functions of a wide range of cellular transcription factors.

Transforming growth factor beta 1 (TGF-β1) modulates Epstein-Barr virus reactivation in absence of Helicobacter pylori infection in patients with gastric cancer.

Background: Transforming growth factor-beta 1 (TGF-β1), a multifunctional cytokine, acts as a key factor for Epstein-Barr virus (EBV) reactivation. We investigated the role of TGF-β1 in latent and lytic stages of EBV in relation to Helicobacter pylori infection among patients with gastric cancer (GC) and peptic ulcer disease (PUD).

Method: Gastric mucosal TGF-β1 expression was determined in 95 EBV positive patients with gastroduodenal pathology [GC 40, PUD 19 and non-ulcer dyspepsia (NUD) 36] by quantitative real time PCR.