Background: Diabetic nephropathy (DNP) is a type 2 diabetes mellitus (T2DM) chronic complication, which is the largest single cause of end-stage kidney disease. There is an increasing evidence of the role of inflammation and Toll-like receptors (TLRs) as part of innate immune system in its development and progression. In addition, Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) downward signaling causes the production of proinflammatory cytokines, which can induce insulin (INS) resistance in T2DM.Objective: The goal of this study was to estimate the expression of TLRs (TLR2 and TLR4) in relation to inflammation and INS resistance in nephrotic type 2 diabetic patients with or without renal failure and to discuss the role of these TLRs in DNP progression.Patients and Methods: In this study, blood samples were obtained from type 2 diabetic patients with or without renal failure, and patients with non-diabetic renal failure were compared to healthy controls. All participants were tested for analysis of fasting plasma glucose and serum insulin, kidney function tests, C-reactive protein (CRP), and proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6) as well as expression of TLR2 and TLR4 in peripheral blood (PB). Statistical analysis of data was done by using SPSS.Results: Diabetic patients with renal failure exhibited significant increase in TLR2, TLR4 mRNA expression in PB in comparison with normal subjects, diabetic patients without renal failure and non-diabetic patients with renal failure. Both diabetic patients with or without kidney failure and non-diabetic patients with renal failure had increased TLR2 and TLR4 mRNA expression in association with increased levels of proinflammatory cytokines (TNF-α, IFN-γ, and IL-6) compared to normal subjects. The diabetic patients with kidney failure exhibited the highest elevation of TLRs, Th1 cytokines and CRP in association the highest record of insulin resistance.Conclusion: Toll-like receptor 2 and Toll-like receptor 4 increased expression and Th2 cytokines may have an important role in the progression of DNP and deteriorations in insulin resistance in type 2 diabetic patients. Therefore, TLR2 and TLR4 may be a promising therapeutic target to prevent or retard DNP in type 2 diabetic patients.

Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. Brassica nigra (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of B. nigra seeds against A549 and H1299 human non-small cell lung cancer cell lines. B. nigra extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. B. nigra extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with B. nigra extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, B. nigra extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, B. nigra extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that B. nigra seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.

Background: COVID-19 impacts the cardiovascular system resulting in myocardial damage, and also affects the kidneys leading to renal dysfunction. This effect is mostly through the binding with angiotensin-converting enzyme 2 (ACE2) and Neuropilin-1 (NRP-l) receptors. Toll-Like Receptors (TLRs) typically combine with microbial pathogens and provoke an inflammatory response. Aim: This work aims to compare the changes in kidney and heart function bioindicators and expressions of TLRs (TLR2 and TLR2) as well as ACE2 and NRP-l receptors in moderate and severe COVID-19 patients. The correlations between kidney and heart function bioindicators and expressions of these receptors are also studied. Patients and Methods: In this study, 50 healthy control and 100 COVID-19 patients (55 males and 45 females) were enrolled. According to WHO guidelines, these participants were divided into severe (50 cases) and moderate (50 cases). Serum creatinine, blood urea, CK-MB, LDH, and Troponin I were estimated. We measured the gene expression for Toll-Like Receptors (TLR2 and TLR4), ACE2, and NRP-1 in the blood samples using quantitative real-time PCR (qRT-PCR). Results: In comparison with the healthy group, all patients exhibited a significant elevation in serum creatinine, urea, cardiac enzymes (CK-MB and LDH), and CRP. Serum Troponin I level was significantly increased in severe COVID-19 patients. Furthermore, all studied patients revealed a significant elevation in the expression levels of TLR2, TLR4, ACE2, and NRP-1 mRNA. In all patients, CK-MB, ACE2, and NRP-1 mRNA expression levels were positively correlated with both TLR2 and TLR4 expression levels. Moreover, serum creatinine and urea levels were positively correlated with both TLR2 and TLR 4 expression levels in the severe group only. In the moderate group, serum CK-MB activity and Troponin I level had a significant positive correlation with both NRP-1 and ACE2 expression levels, while serum urea level and LDH activity had a significant positive correlation with NRP-1 only. In severe patients, the increases in serum creatinine, urea, CK-MB, and LDH were significantly associated with the elevations in both ACE2 and NRP-1 expression levels, whereas serum Troponin I level had a positive direct relationship with NRP-1 only. Conclusions: Our study concluded that expression levels for TLR2, TLR4, ACE2, and NRP-1 mRNA in both severe and moderate patients were positively correlated with renal biomarkers and cardiac enzymes. Innate immune markers can be important because they correlate with the severity of illness in COVID-19.

Biosynthesis of nanoparticles is a valuable method and highly safe with low cost. Gold nanoparticles have an enormous medical application, in recent days. This study demonstrates an optimized biosynthesis for stable gold nanoparticles (AuNPs) using Pleurotus ostreatus extracellular filtrate. The biosynthesized gold nanoparticles characterization using UV-Vis spectrophotometer, Zeta seizer, X-ray diffraction, TEM, and FTIR. UV-Vis spectra of gold nanoparticles showed maximum absorption peak at 550 nm. From the TEM images, the size of AuNPs was found to be about 10−30 nm. The physicochemical parameters of gold nanoparticles biosynthesis were studied using Plackett-Burman design. All parameters were highly significant (p < 0.001). The rate of AuNPs biosynthesis was found to increase with increasing the salt concentration, incubation time and temperature. On the other hand, lowering both the pH and ratio increase the biosynthesis rate. Furthermore, we compared the anti-proliferation of the biosynthesized and the commercial prepared AuNPs against human liver cancer cell line (HepG2), Prostate cancer cell line (PC3) and Human colon cancer cell line (HCT-116). The biosynthesized AuNPs caused a significant decrease in cell viability of both HepG2 and HCT-116 (33.5%, 22.7%) than commercial AuNPs (29.7%, 9.8%). The synergistic effect of biosynthesized AuNPs gave highest fold increase (11) against E. coli, followed by (10) fold against Staphylococcus auras using Azithromycin and Amoxicillin as standard antibiotics respectively.

Background: Higher expression of angiotensin-converting enzyme-2 (ACE-2) in addition to neuropilin-1 (NRP-1) can lead to a cytokine storm which is correlated to higher mortality rate and contributes to the progression of renal diseases and the pathogenesis of coronary heart disease (CHD) in COVID-19 patients. Aim: We herein sought to examine correlations between cytokine levels, ACE-2 and NRP-1 expression, renal function biomarkers, and cardiac enzymes in COVID-19 patients. Patients and Methods: For the study, 50 healthy subjects and 100 COVID-19 patients were enrolled. Then, confirmed cases of COVID-19 were divided into two groups—those with moderate infection and those with severe infection—and compared to healthy controls. Serum creatinine, urea, CK-MB, LDH, troponin I, IL-1β, IL-4, IL-10, IL-17, and INF-γ levels were estimated. We also studied the gene expression for ACE-2 and NRP-1 in blood samples utilizing quantitative real-time polymerase chain reaction (qRT-PCR). Results: All COVID-19 patients demonstrated a significant increase in the levels of serum creatinine, urea, CK-MB, LDH, and troponin I, as well as examined cytokines compared to the healthy controls. Furthermore, ACE-2 mRNA and NRP-1 mRNA expression levels demonstrated a significant increase in both severe and moderate COVID-19 patient groups. In the severe group, serum creatinine and urea levels were positively correlated with IL-10, INF-γ, NRP-1, and ACE-2 expression levels. Moreover, LDH was positively correlated with all the examined cytokine, NRP-1, and ACE-2 expression levels. Conclusion: Deficits in renal and cardiac functions might be attributable to cytokine storm resulting from the higher expression of ACE-2 and NRP-1 in cases of COVID-19.