Silencing Nrf2 in cisplatin resistant non-small cell lung cancer cells augments sensitivity towards EGFR inhibitor.

Recently, non-small cell lung cancer (NSCLC) has been the prime concern of cancer clinicians due to its high mortality rate worldwide. Cisplatin, a platinum derivative, has been used as a therapeutic option for treating metastatic NSCLC for several years. However, acquired, or intrinsic drug resistance to Cisplatin is the major obstacle to the successful treatment outcome of patients.

Adipocyte Mitochondria: Deciphering Energetic Functions across Fat Depots in Obesity and Type 2 Diabetes.

Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D). Mitochondrial dysfunction within adipocytes leads to inefficient lipid handling and increased oxidative stress, which together promote systemic metabolic disruptions central to obesity and its complications. This review explores the pivotal role that mitochondria play in altering the metabolic functions of the primary adipocyte types, white, brown, and beige, within the context of obesity and T2D.

Nrf2 inhibition regulates intracellular lipid accumulation in mouse insulinoma cells and improves insulin secretory function.

High amount of fat in the pancreas is linked to poor functioning of β-cells and raises the risk of type 2 diabetes. Here we report the putative role of a circulatory glycoprotein Fetuin-A, a known obesity marker, in promoting lipid accumulation in β-cells and its association with Fatty acid translocase/CD36 for lipid storage culminate in β-cell dysfunction. Additionally, this work reveals regulation of CD36 via Nrf2, a key regulator of oxidative stress, and reduction of lipid accumulation by suppression of Nrf2 that restores β-cell function.

Reliable fluorescence technique to detect the antibiotic colistin, a possible environmental threat due to its overuse.

Colistin, considered a drug of last resort as it is effective towards multidrug-resistant Gram-negative bacterial infections. Oral administration of colistin in the poultry industry is a common practice, not only to prevent and reduce bacterial infections, but also as a rapid-growth promoter. Long-term exposure to any antibiotic will eventually lead to the development of bacterial resistance towards all antibiotics through various mechanisms in the physiological system and environment.

Fetuin-A secretion from β-cells leads to accumulation of macrophages in islets, aggravates inflammation and impairs insulin secretion.

Elevated fetuin-A levels, chemokines and islet-resident macrophages are crucial factors associated with obesity-mediated type 2 diabetes (T2D). Here, the aim of the study was to investigate the effect of MIN6 (a mouse insulinoma cell line)-derived fetuin-A (also known as AHSG) in macrophage polarization and decipher the effect of M1 type pro-inflammatory macrophages in commanding over insulin secretion. MIN6 and islet-derived fetuin-A induced expression of the M1 type macrophage markers Emr1 (also known as Adgre1), Cd68 and CD11c (Itgax) (∼1.

Exploring the Propensities of Fluorescent Carbazole Analogs toward the Inhibition of Amyloid Aggregation in Type 2 Diabetes: An Experimental and Theoretical Endeavor.

Amyloid aggregation is a pathological trait observed in many incurable and fatal neurodegenerative and metabolic diseases associated with misfolding and self-assembly of various proteins. Noncovalent interactions between these structural motifs and small molecules can, however, prevent this aggregation. Herein, five structurally different synthetic (Cz1-Cz4) and naturally occurring (Cz5, mahanimbine) fluorescent carbazole analogs are explored for their comparative amyloid aggregation inhibitory activities.

Fetuin-A excess expression amplifies lipid induced apoptosis and β-cell damage.

Fetuin-A, a hepato-adipokine, is associated with lipid-mediated islet inflammation and inflicts β-cell death but the underlying mechanisms are still unclear. In an earlier report, it was shown that fetuin-A promotes lipid-induced insulin resistance by acting as an endogenous ligand of toll like receptor 4. Recently, we have also reported that β-cells secrete fetuin-A on stimulation by palmitate causing β-cell dysfunction.

Blocking TLR4-NF-κB pathway protects mouse islets from the combinatorial impact of high fat and fetuin-A mediated dysfunction and restores ability for insulin secretion.

Lipid mediated pancreatic β-cell dysfunction during Type 2 diabetes is known to be regulated by activation of TLR4 (Toll Like Receptor 4) and NF-κB (Nuclear factor kappa B). Recently we have reported that MIN6 cells (mouse insulinoma cells) secrete fetuin-A on stimulation by palmitate that aggravates β-cell dysfunction, but the mechanism involved in-vivo has not been demonstrated and thus remained unclear. Here we attempted to dissect the role of palmitate and fetuin-A on insulin secretion using high fat diet (HFD) fed mice model.

Kaempferol inhibits Nrf2 signalling pathway via downregulation of Nrf2 mRNA and induces apoptosis in NSCLC cells.

Chemoprevention failure is considered to be the most emerging problem that makes non-small cell lung cancer (NSCLC) as one of the deadliest malignancies in the world. In NSCLC cells, Nuclear factor erythroid 2-related factor 2 (Nrf2), a redox sensitive transcription factor, promotes cancer cell survival and fosters mechanism for drug resistance. Here we report identification of Kaempferol, a dietary flavonoid, as a potent Nrf2 inhibitor using Nrf2 reporter assay in NSCLC cells (A549 and NCIH460).

Unfolding the Role of a Flavone-Based Fluorescent Antioxidant towards the Misfolding of Amyloid Proteins: An Endeavour to Probe Amyloid Aggregation.

4'-,-Dimethylamino-3-hydroxyflavone (DMAHF), a synthetic fluorescent flavone analogue with potent antioxidant activity, was explored as a molecular rotor-like fluoroprobe for amyloid aggregations, a causative factor in Alzheimer's disease, Parkinson's disease, type-2 diabetes, etc. During its interactions with (human) insulin amyloid aggregation (IAA), its microenvironment was changed. This instigated a drastic change in its excited-state intramolecular proton transfer-based dual emission behavior, which was tracked to monitor its amyloid probing activity.

Trigonelline inhibits Nrf2 via EGFR signalling pathway and augments efficacy of Cisplatin and Etoposide in NSCLC cells.

Constitutive high expression of Nrf2 (Nuclear factor erythroid 2-related factor 2) is an important contributor of proliferation and chemoresistance in Non-small cell lung cancer (NSCLC). The aim of this present study was to investigate the Nrf2 inhibitory effect of Trigonelline, its mechanism of action and its possible use in combinatorial treatment with anti- lung cancer drugs, Cisplatin and Etoposide. Our immunofluorescence, western blot and real time PCR data showed that Trigonelline prevented nuclear accumulation of pNrf2 (four folds) and downregulated Nrf2 targeted genes in both A549 and NCIH460 cells.

Designed Synthesis of Dual Emitting Silicon Quantum Dot for Cell Imaging: Direct Labeling of Alpha 2-HS-Glycoprotein.

The innocent silicon quantum dots (SQDs) having dual emissive property (blue in VIS and red in NIR), high photostability, and freedom from auto fluorescence are designed and synthesized for the first time using ethylene glycol. A new attempt has been made for direct labeling of Alpha 2-HS-Glycoprotein (Fetuin A) through functionalization of the synthesized dots by EDC coupling. The SQDs were characterized by FTIR, TEM, AFM, XRD, EDX, DLS, and TGA.

Palmitate induced Fetuin-A secretion from pancreatic β-cells adversely affects its function and elicits inflammation.

Islets of type 2 diabetes patients display inflammation, elevated levels of cytokines and macrophages. The master regulator of inflammation in the islets is free fatty acids (FFA). It has already been reported that FFA and TLR4 stimulation induces pro-inflammatory factors in the islets.