Investigating the Role of Acacia Nilotica Nanoparticles on Promoting Apoptosis in Human Breast Cancer Cell Line (MDA-MB-231)

MDA-MB-231 is a model of a human breast cancer cell line. It represents a suitable cell line for breast cancer research worldwide, including anti-cancer studies. Natural products are rich in phytochemicals that have anti-cancer, antioxidant and anti-inflammatory effects. The aim of this study was to characterize the Acacia nilotica nanoparticles (AN-NPs) from the extract of Acacia nilotica (AN) using transmission electron microscopy (TEM), zeta sizer, X-ray diffraction (XRD) and Fourier transform infrared (FT-IR). Cytotoxic activity was assessed using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The morphological changes of the cells were examined using an inverted microscope. The results showed that at serial concentrations (5, 10, 20, 50 and 70 µg/ml) of AN extract and AN-NPs, a cytotoxic effect and morphological degeneration and damage of the cells were observed. The effect varied depending on the exposure time and AN extract and/or AN-NP concentration on MDA-MB-231. The results showed cytotoxic effects, morphological degeneration, damage and more efficacy against breast cancer cells. We can conclude that AN extract and AN-NP are an effective choice for the development of pharmacological treatments against cancer

PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

The role of IL-1β in regulating the expression and secretion of cytokines and chemokines by human adipocytes was examined. Adipocytes were incubated with human IL-1β for 4 or 24 h. The expression of a panel of 84 cytokine/chemokine genes was probed using PCR arrays. IL-1β stimulated the expression of >30 cytokine/chemokine genes on the arrays; 15 showed >100-fold increases in mRNA at 4 or 24 h including CSF3, CXCL1, CXCL2, CXCL12 and IL8. CSF3 exhibited a 10,000-fold increase in mRNA at 4 h. ADIPOQ was among the genes whose expression was inhibited. Protein arrays were used to examine the secretion of cytokines/chemokines from adipocytes. IL-1β stimulated the secretion of multiple cytokines/chemokines including MCP-1, IL-8, IP-10, MIP-1α and MCP-4. The most responsive was IP-10, which exhibited a 5,000-fold increase in secretion with IL-1β. IL-1β is likely to play a substantial role in stimulating the inflammatory response in human adipocytes in obesity

Cross talk between complete blood count and progression of type II diabetes mellitus

Background: Diabetes mellitus (DM) is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. The most common type is type II diabetes and is characterized by insulin resistance or relative insulin deficiency. Objectives: This study was performed to discover whether Complte blood count is a suitable indicator for development of type II diabetes complications. Methods: 137 type II diabetic patients with high blood glucose level were included in this study and their complete blood count was recorded. Demographic and laboratory data were also noted. Result: WBC, Hb, Hematocrit, MCH had abnormal values. As the results of this study show, higher leukocyte counts was correlated with uncontrolled diabetes. Accompanied by other markers, chronic inflammation that can be shown by this factor could be related to pathogenesis and the progression of these diabetes-related complications. Conclusion: Complete blood count test could be considered as an appropriate clinical examination for early diagnosis and prevention of microvascular and macrovascular complications thus reducing morbidity and mortality from diabetes mellitus

Potential histopathological and molecular changes in rat vas deferens inhaled by Boswellia papyrifera and Boswellia carterii

Boswellia papyrifera and Boswellia carterii released from smoke contaminate indoor environment and consequently adversely affect humans as evidenced by respiratory disturbances. The aim of this study was to determine the effects of these plants on pathological and biochemical changes in vas deferens of albino rats. Animals were administered 4g/kg body weight B. papyrifera and B. carterii daily for 120days along with controls. Significant changes were observed in epithelial cell types and some cells showed signs of degeneration. The ultrastructural studies revealed marked changes in cytoplasmic organelles. Microvilli were missing and lysosomes were found in the cytoplasm. In addition, all treated groups plasma fructose and other biochemical parameters were decreased indicating reduced energy necessary for motility and contractility of spermatozoa. Many spermatozoa were disorganized and agglomerated. Data suggest that smoke from these plants adversely affects vas deferens

Relationship between KIR genotypes and HLA-ligands with SARS-CoV-2 infection in the Saudi population

Aim: To ascertain whether killer cell immunoglobulin-like receptors (KIR) genes polymorphisms and HLA-I ligands are associated with COVID-19 in Saudi Arabia. Methods: Eighty-seven COVID-19 patients who tested positive for SARS-CoV-2 and one hundred and fourteen healthy controls were enrolled in this study for genotyping of the 16 KIR genes, HLA-C1 and -C2 allotypes and HLA-G 14-bp indels polymorphisms using the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency differences and combination KIR-HLA-C ligand were tested for significance. Results: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIR3DP2 were present in all individuals. The frequencies of KIR2DL2 and KIR2D4 were higher in COVID-19 positive patients than in healthy individuals. The frequencies of the combination KIR2DL2-HLA-C2 was also significantly higher in patients affected by COVID-19 compared with healthy controls. Conclusion: It was found that the inhibitory KIR2DL2 gene in isolation or combined with its HLA-C2 ligand could be associated with susceptibility to COVID-19 in the Saudi population

Association of IL-1β, IL-6, TNF-α, and TGFβ1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome

Recurrent spontaneous abortion (RSA) is a common pregnancy-associated complication of polycystic ovary syndrome (PCOS) which is an endocrine malfunction disease. Patients with PCOS may have several underlying contributing and interrelated factors, which have been reported in women with RSA. The incidence rate between PCOS and RSA remains uncertain. The aim of this study is to determine the possible association of IL-1β-511C/T, IL-6-174G/C, TNF-α-1031T/C, and TGFβ1-509T/C with RSA patients with or without PCOS. A total of 140 RSA patients, 70 of which were PCOS patients, and 140 healthy females with no history of RSA or PCOS were included in this study. PCR amplification, genotyping, and sequence analysis were employed to investigate the presence of the polymorphisms. The genotypic and allelic frequencies were calculated separately for each subject. Out of the four studied polymorphisms, the IL-1β-511C/T genotype in RSA without PCOS patients (12.7%) was significantly different compared with that in control subjects (p=0.047). For IL-6-174C/G, there was a tendency towards more CC carriers among RSA with PCOS patients (10%) than in controls (3%). The GG genotype in RSA women with PCOS (60%) was significantly different compared with that in control subjects (p=0.033), and the GC genotype in RSA with PCOS patients (30%) showed a marginal significant difference compared with that in control subjects (p=0.050). Significant difference was identified in the allelic frequencies in RSA patients with PCOS compared to controls (p=0.025). IL-6-174G/C and TNF-α-1031T/C polymorphisms are significantly associated with RSA patients in Saudi patients with PCOS, while the IL-1β-511C/T polymorphism is significantly associated with RSA patients without PCOS

Discovery of putative inhibitors against main drivers of SARS-CoV-2 infection: Insight from quantum mechanical evaluation and molecular modeling

International audienceSARS-CoV-2 triggered a worldwide medical crisis, affecting the world’s social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19’s threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski’s rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein–ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein–ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein–ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation