Visible Light-Mediated Co(II) Catalyzed Synthesis of Epoxy Ketones by Oxidative Coupling of Alkenes and Aldehydes in Water.

A one-step, two-component visible light-mediated CoCl·6HO-catalyzed oxidative acylation of alkenes by aldehydes to synthesize -epoxy ketone has been achieved in water at room temperature. The photocatalytic activity of Co(II) presented a remarkable achievement for synthesis of -epoxy ketones from aldehydes and olefins, with a wide substrate compatibility including aromatic, heteroaromatic and aliphatic aldehydes, styrenes with both electron-donating and withdrawing groups, α-substituted styrenes, stilbene, acrylates, and even the challenging unactivated aliphatic alkenes. Mechanistic studies including radical trapping experiments, intermediate detection by GCMS, Hammett analysis, and DFT studies unveil the nature of the photocatalytic pathway.

Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.

Unlabelled: Combinatorial molecular therapy in pancreatic ductal adenocarcinoma (PDAC) has yielded largely disappointing results in clinical testing to-date as a multitude of adaptive resistance mechanisms is making selection of patients via molecular markers that capture essential, intersecting signaling routes challenging. Here, we report the scaffolding protein connector enhancer of kinase suppressor of Ras 1 (CNKSR1) as mediator of resistance to MAPK (MEK) inhibition. MEK inhibition in CNKSR1high cancer cells induces translocation of CNKSR1 to the plasma membrane where the scaffolding protein interacts with and stabilizes the phosphorylated form of AKT.

Evaluation of levels of oxidative stress as a potential biomarker in patients with rheumatoid arthritis.

Objectives: One of the most prevalent autoimmune disease globally, rheumatoid arthritis (RA) is caused by interplay of multiple inflammatory mediators in specific joints. Altered redox balance is one of the key factors in pathophysiology of RA. This study aims to find whether oxidative stress in peripheral blood neutrophil correlates with the disease activity and disability associated with it.

Generation of a robust model for inducing autoimmune arthritis in Sprague Dawley rats.

Introduction: The prerequisite for any experimental model in animals is similarity with the human disease, uniformity in disease severity and incidence. In antigen-induced arthritis models it is generally recognized that the major limitation is inconsistency in terms of incidence and severity. As access to strains like DBA/1 mice or Lewis rats is difficult for resource restrained laboratories, this study aimed to establish a robust and reproducible animal model of rheumatoid arthritis (RA).

Role of redox imbalance and cytokines in mediating oxidative damage and disease progression of patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder wherein the contributory role of oxidative stress has been established in the synovial fluid. As availability of synovial fluid is limited, this study aimed to evaluate in the peripheral blood of patients with RA, the relationship if any, between the extent of oxidative stress in terms of generation of reactive oxygen species (ROS) in neutrophils, plasma NADPH oxidase and myeloperoxidase activity with markers of oxidative damage, circulating cytokines and disease activity score (DAS28). In patients with RA, neutrophils in peripheral blood demonstrated an enhanced generation of ROS, coupled with depletion of free radical scavenging activity.

Allylpyrocatechol attenuates methotrexate-induced hepatotoxicity in a collagen-induced model of arthritis.

The cornerstone of treatment for rheumatoid arthritis is low dose methotrexate (MTX), but its use is limited by concerns regarding its potential for hepatotoxicity. Allylpyrocatechol (APC), a phytoconstituent sourced from leaves of Piper betle demonstrated antioxidant, anti-inflammatory, and antiarthritic properties. The present study aimed to evaluate the combined effect of APC and MTX on limiting progression of lipopolysaccharide accelerated collagen-induced arthritis, along with reduction of MTX-induced hepatic damage.

Allylpyrocatechol Attenuates Collagen-Induced Arthritis via Attenuation of Oxidative Stress Secondary to Modulation of the MAPK, JAK/STAT, and Nrf2/HO-1 Pathways.

Rheumatoid arthritis (RA), an inflammatory autoimmune disorder, is characterized by synovial hyperplasia and bony destruction. The pathogenesis of RA includes redox dysregulation, concomitant with increased levels of proinflammatory mediators. As the ability of allylpyrocatechol (APC), a phytoconstituent of Piper betle leaves, to alleviate oxidative stress has been demonstrated in patients with RA, its antiarthritic activity was evaluated in an animal model of arthritis, and the underlying mechanism(s) of action clarified.

Impact of MAPK and PI3K/AKT signaling pathways on Malabaricone-A induced cytotoxicity in U937, a histiocytic lymphoma cell line.

Intrinsically cancer cells have higher basal levels of reactive oxygen species (ROS), which when augmented by pro-oxidants such as Malabaricone-A (MAL-A) triggers apoptotic cell death, secondary to 'turning on' of the apoptosis related cell signaling pathways. The effects of MAL-A upon key inflammation related signaling molecules were evaluated by western blotting in U937, a histiocytic lymphoma derived cell line. The impact of inhibitors of the pro-apoptotic MAPK and anti-apoptotic PI3K/AKT signaling pathways upon MAL-A induced cytotoxicity and generation of ROS was evaluated by a cell viability assay and flow cytometry respectively in two hematopoietic cell lines, U937 and MOLT3.

Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.

The variable chemotherapeutic response of Malabaricone-A in leukemic and solid tumor cell lines depends on the degree of redox imbalance.

Purpose: The 'two-faced' character of reactive oxygen species (ROS) plays an important role in cancer biology by acting as secondary messengers in intracellular signaling cascades, enhancing cell proliferation and survival, thereby sustaining the oncogenic phenotype. Conversely, enhanced generation of ROS can trigger an oxidative assault leading to a redox imbalance translating into an apoptotic cell death. Intrinsically, cancer cells have higher basal levels of ROS which if supplemented by additional oxidative insult by pro-oxidants can be cytotoxic, an example being Malabaricone-A (MAL-A).

Can systemically generated reactive oxygen species help to monitor disease activity in generalized vitiligo? A pilot study.

Background: Generalized vitiligo is a disease with unpredictable bursts of activity, goal of treatment during the active phase being to stabilize the lesions. This emphasizes the need for a prospective marker for monitoring disease activity to help decide the duration of therapy.

Aims And Objectives: In the present study, we examined whether reactive oxygen species (ROS) generated in erythrocytes can be translated into a marker of activity in vitiligo.

Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease whose etiology remains unknown, but studies have consistently implicated a plethora of inflammatory mechanisms culminating in chronic symmetric and erosive synovitis. Importantly, reactive oxygen species (ROS) have been attributed to directly contribute towards the destructive, proliferative synovitis evident in RA. Accordingly, this study aimed to establish whether the degree of oxidative stress and disease activity score (DAS28) correlated with the downstream effects of oxidative damage.

Combination of vildagliptin and rosiglitazone ameliorates nonalcoholic fatty liver disease in C57BL/6 mice.

Objectives: To evaluate the effect of vildagliptin alone and in combination with metformin or rosiglitazone on murine hepatic steatosis in diet-induced nonalcoholic fatty liver disease (NAFLD).

Materials And Methods: Male C57BL/6 mice were fed with high fat diet (60 Kcal %) and fructose (40%) in drinking water for 60 days to induce NAFLD. After the induction period, animals were divided into different groups and treated with vildagliptin (10 mg/kg), metformin (350 mg/kg), rosiglitazone (10 mg/kg), vildagliptin (10 mg/kg) + metformin (350 mg/kg), or vildagliptin (10 mg/kg) + rosiglitazone (10 mg/kg) orally for 28 days.

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway.

Objectives: The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action.

Materials And Methods: Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.

The antioxidant activity of allylpyrocatechol is mediated via decreased generation of free radicals along with escalation of antioxidant mechanisms.

Allylpyrocatechol (APC) is responsible for the antiinflammatory activity exhibited by the methanolic extract of leaves of Piper betle. As antiinflammatory compounds may display antioxidant properties and vice versa, we investigated the antioxidant effect of APC. APC effectively reduced phorbol-myristate-acetate-induced generation of reactive oxygen species and superoxide in murine peritoneal macrophages as well as inhibited Escherichia-coli-induced phagocytic activity of macrophages.