AKR1B1 drives hyperglycemia-induced metabolic reprogramming in MASLD-associated hepatocellular carcinoma.

Background & Aims: The mechanism behind the progressive pathological alteration in metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH)-associated hepatocellular carcinoma (HCC) is poorly understood. In the present study, we investigated the role of the polyol pathway enzyme AKR1B1 in metabolic switching associated with MASLD/MASH and in the progression of HCC.

Methods: AKR1B1 expression was estimated in the tissue and plasma of patients with MASLD/MASH, HCC, and HCC with diabetes mellitus.

Molecular dissection of anti-colon cancer activity of NARI-29: special focus on HO modulated NF-κB and death receptor signaling.

Accumulating evidence attributes the role of aldose reductase (AR) in modulating ROS and inflammation which are the main factor responsible for cancer progression and drug resistance. Epalrestat is the only AR inhibitor being used in Asian countries. It did not make it to the markets of the USA and Europe due to marginal efficacy as an antioxidant and anti-inflammatory agent owing to difficulty reaching intracellular targets.

AKR1B1 inhibition using NARI-29-an Epalrestat analogue-alleviates Doxorubicin-induced cardiotoxicity via modulating Calcium/CaMKII/MuRF-1 axis.

The clinical use of doxorubicin (Dox) is narrowed due to its carbonyl reduction to doxorubicinol (Doxol) implicating resistance and cardiotoxicity. Hence, in the present study we have evaluated the cardioprotective effect of AKR1B1 (or aldose reductase, AR) inhibitor NARI-29 (epalrestat (EPS) analogue) and its effect in the Dox-modulated calcium/CaMKII/MuRF1 axis. Initially, the breast cancer patient survival associated with AKR1B1 expression was calculated using Kaplan Meier-plotter (KM-plotter).

Pivotal role of AKR1B1 in pathogenesis of colitis associated colorectal carcinogenesis.

Identifying the target linking inflammation and oxidative stress to aggravate the disease progression will help to prevent colitis associated carcinogenesis. Since AKR1B1 overexpression is observed in inflammatory diseases and various cancers, we have investigated the role of AKR1B1 in colitis-associated colon carcinogenesis with the aid of epalrestat and its potent analogue NARI-29 (investigational molecule) as pharmacological probes. A TNF-α inducible NF-κB reporter cell line (GloResponse™ NF-κB-RE-luc2P HEK293) and dextran sodium sulfate (DSS) and 1,2 dimethyl hydrazine (DMH))-induced mouse model was used to investigate our hypothesis in vitro and in vivo.

2-Cyano-3-(2-thienyl)acrylic Acid as a New MALDI Matrix for the Analysis of a Broad Spectrum of Analytes.

A low-cost synthetic 2-cyano-3-(2-thienyl)acrylic acid (CTA) is developed as a new MALDI matrix for the analysis of various classes of compounds such as lipids (e.g., fatty acids), peptides, proteins, saccharides, natural products (i.

Fixing Transient Iodine on Developed Latent Fingermarks.

In the present study, a simple and novel fume-mist technique is described which can be used efficiently to fix the latent fingermarks developed using iodine. It is well known that the residues left over in the fingermarks interact with iodine to give transient brown impressions which disappear in a short time. Also, iodine forms colored complexes with various organic solvents.

Carbonyl Compounds' Journey to Amide Bond Formation.

The formation of amide bonds is one of the most stimulating emerging areas in organic and medicinal chemistry. Amides are recognized as central building blocks in a plethora of interesting pharmaceuticals, proteins, peptides, polymers, natural products, functional materials, and biologically relevant carbocyclic or heterocyclic molecules, and they are also found in a variety of industrial fields. Therefore, a review of recent developments and challenges in the formation of amide bonds from carbonyl compounds is particularly important.

Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function.

Background and Purpose- Acetylsalicylic acid and clopidogrel are the 2 main antithrombotic drugs for secondary prevention in patients with ischemic stroke (IS) without indication for anticoagulation. Because of their limited efficacy and potential side effects, novel antiplatelet agents are urgently needed. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor, protected from IS in clinical studies comprising mainly Asian populations.

IITZ-01, a novel potent lysosomotropic autophagy inhibitor, has single-agent antitumor efficacy in triple-negative breast cancer in vitro and in vivo.

Autophagy is a homeostatic process that recycles damaged organelles and long-lived proteins by delivering them in double-membrane vesicles to lysosomes for degradation. Autophagy has a prominent role in survival, proliferation, and resistance of tumors in metabolic and chemotherapeutic stress conditions. Clinical trials with chloroquine-a known autophagy inhibitor-were unable to achieve complete autophagy inhibition in vivo, warranting the search for more potent autophagy inhibitors.

A pyrene formulation for fluorometric visualization of latent fingermarks.

Present work is conducted to demonstrate the use of pyrene for the development of latent fingermarks. Pyrene formulation with binders can be efficiently used for developing latent fingermarks on porous, non-porous and semi-porous surfaces. The effectiveness of pyrene formulation for the detection of latent fingermarks present on a large variety of objects was systematically and comparatively carried out.

Dithieno[3,2-b:2',3'-d]pyrrole-benzo[c][1,2,5]thiadiazole conjugate small molecule donors: effect of fluorine content on their photovoltaic properties.

Two new small molecule donors, namely ICT4 and ICT6 with D-A-D-A-D architecture having 2,4-bis(2-ethylhexyl)-4H-dithieno[3,2-b:2',3'-d]pyrrole (EHDTP, D) and 4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b']dithiophene (OBDT, D) as the terminal and central donor, and benzo[c][1,2,5]thiadiazole (BT for ICT4) and 5,6-difluorobenzo[c][1,2,5]thiadiazole (F2BT for ICT6) as the acceptor (A) moieties, are synthesized and their optical, electronic and photovoltaic properties are investigated. Both ICT4 and ICT6 have considerable solubility in various solvents and possess efficient light absorption ability [ε (×10 mol cm) is 0.99 and 1.

A dithieno[3,2-b:2',3'-d]pyrrole based, NIR absorbing, solution processable, small molecule donor for efficient bulk heterojunction solar cells.

A novel, NIR absorbing organic small molecular donor material denoted as ICT3 with an A-D-D-D-A architecture having dithieno[3,2-b:2',3'-d]pyrrole (DTP) and butylrhodanine as donor and acceptor moieties, respectively, is synthesized and its thermal, photophysical, electrochemical and photovoltaic properties are explored. ICT3 has excellent stability over a broad range of temperatures with a decomposition temperature (T corresponds to 5% weight loss) of 372 °C, soluble in most common organic solvents (solubility up to 30 mg mL) and suitable for solution processing during device fabrication. ICT3 has broad (520-820 nm) and intense visible region absorption (molar excitation coefficient is 1.

2-Azetidinones: Synthesis and biological evaluation as potential anti-breast cancer agents.

A series of twenty-five 2-azitidinone (β-lactam) derivatives were synthesized and evaluated for anti-cancer properties against breast cancer, MCF-7 and MDA-MB-231. These β-lactam derivatives depicted significant cytotoxicity in cancer cell lines but not in normal human mammary epithelial cells, MEpiC. Interestingly, derivatives of 2-bromo ethyl acrylonitrile (19w) exhibited - potent anti-proliferative activity with IC, 5.

Synthesis and biological evaluation of new rhodanine analogues bearing 2-chloroquinoline and benzo[h]quinoline scaffolds as anticancer agents.

Several rhodanine derivatives (9-39) were synthesized for evaluation of their potential as anticancer agents. Villsmeier cyclization to synthesize aza-aromatic aldehydes, rhodanine derivatives preparation and Knoevenagel type of condensation between the rhodanines and aza-aromatic aldehydes are key steps used for the synthesis of 31 compounds. In vitro antiproliferative activity of the synthesized rhodanine derivatives (9-39) was studied on a panel of six human tumor cell lines viz.

Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors.

A series of thio-substituted pyrimidine, benzoxazole, benzothiazole and triazole analogues were synthesized from Baylis-Hillman bromides in a clean and efficient way. The synthesized twenty new compounds were subjected to in vitro COX-1 and COX-2 inhibitory activity. Majority of compounds found to be highly selective COX-2 inhibitor.

Synthesis, antitubercular and anticancer activity of new Baylis-Hillman adduct-derived -cinnamyl-substituted isatin derivatives.

Baylis-Hillman adduct-derived -cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on HRv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (-) have shown significant activity against strain and the compound has shown specific cytotoxic activity.

Simultaneous determination of atorvastatin, amlodipine, ramipril and benazepril in human plasma by LC-MS/MS and its application to a human pharmacokinetic study.

A rapid, simple, sensitive and specific LC-MS/MS method has been developed and validated for the simultaneous estimation of atorvastatin (ATO), amlodipine (AML), ramipril (RAM) and benazepril (BEN) using nevirapine as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Analytes and IS were extracted from plasma by simple liquid-liquid extraction technique using ethyl acetate.