Modified Citrus Pectin (MCP) Confers a Renoprotective Effect on Early-Stage Nephropathy in Type-2 Diabetic Mice.

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a ß-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-ßRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators.

Dapoxetine prevents neuronal damage and improves functional outcomes in a model of ischemic stroke through the modulation of inflammation and oxidative stress.

Stroke is a medical emergency that is associated with substantial mortality and functional disability in adults. The most popular class of antidepressants, selective serotonin reuptake inhibitors SSRIs, have recently been shown in studies to have positive effects on post-stroke motor and cognitive function. Thus, we hypothesized that dapoxetine (DAP), a short-acting SSRI, would be effective against cerebral ischemia/reperfusion injury. Adult male Wister rats (200-250 g) were subjected to a sham operation or bilateral common carotid artery occlusion (BCCAO) for 30 min followed by 24 h of reperfusion to induce global cerebral ischemia/reperfusion (I/R) injury. Rats were treated with vehicle or DAP (30 or 60 mg/kg, i.p.) 1 h before BCCAO. The neurobehavioral performance of rats was assessed. The infarct volume, histopathological changes, oxidative stress parameters, and apoptotic and inflammatory mediators were determined in the brain tissues of euthanized rats. Our results confirmed that DAP significantly ameliorated cerebral I/R-induced neurobehavioral deficits, reduced cerebral infarct volume, and histopathological damage. Moreover, DAP pretreatment reduced lipid peroxidation, caspase-3, and inflammatory mediators (TNF-α and iNOS) compared to I/R-injured rats. Thus, DAP pretreatment potentially improves neurological function, and cerebral damage in cerebral ischemic rats may be partly related to the reduction in the inflammatory response, preservation of oxidative balance, and suppression of cell apoptosis in brain tissues.

Interferon-λ3 rs12979860 can regulate inflammatory cytokines production in pulmonary fibrosis.

Pulmonary fibrosis (PF) is the last phase of interstitial lung diseases (ILDs), which are a collection of pulmonary illnesses marked by parenchymal remodeling and scarring. Treatment can only halt the functional decline of the lung, raising the necessity of identifying the basic processes implicated in lung fibrogenesis. The Interferon lambda-3 (IFNL3) gene variant, rs12979860, was determined to be related to an elevated risk of fibrosis in different organs, but the mechanism through which it mediates fibrogenesis is not clear. In the current research, we aim to figure out some of the mechanistic pathways by which IFN-λ3 mediates ILDs. 100 healthy controls and 74 ILD patients were genotyped for IFNL3 rs12979860. Then the mRNA expression of IFNL3 and some other proinflammatory mediators was examined according to genotype in the peripheral blood mononuclear cells (PBMCs) of ILDs patients. The IFNL3 rs12979860 genotype distribution of healthy individuals and ILDs patients was shown to be in Hardy-Weinberg equilibrium (HWE) with a minor allele frequency (MAF) of 0.293 and 0.326, respectively. Furthermore, the CC genotype was demonstrated to be linked to enhanced IFNL3 expression. Also, the CC genotype was linked to an increase in the mRNA expression of TLR4 (P = 0.03) and the inflammatory cytokines IL-1ß and TNF-α (P = 0.01 and 0.04, respectively) and had no effect on the NF-kB level (P = 0.3). From these results, we can deduce that IFN-λ3 may mediate tissue fibrosis via increasing the expression of IFN-λ3 itself and other proinflammatory mediators. This stimulates a self-sustaining loop mechanism which includes a reciprocal production of IFN-λ3, TLR4, IL-1ß, and TNF-α leading to persistent inflammation and fibrosis.

Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines.

The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.