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

High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats.

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson's Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life

Surface engineered mesoporous silica carriers for the controlled delivery of anticancer drug 5-fluorouracil: Computational approach for the drug-carrier interactions using density functional theory

Introduction: Drug delivery systems are the topmost priority to increase drug safety and efficacy. In this study, hybrid porous silicates SBA-15 and its derivatives SBA@N and SBA@3N were synthesized and loaded with an anticancer drug, 5-fluorouracil. The drug release was studied in a simulated physiological environment.Method: These materials were characterized for their textural and physio-chemical properties by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), small-angle X-ray diffraction (SAX), and nitrogen adsorption/desorption techniques. The surface electrostatics of the materials was measured by zeta potential.Results: The drug loading efficiency of the prepared hybrid materials was about 10%. In vitro drug release profiles were obtained in simulated fluids. Slow drug release kinetics was observed for SBA@3N, which released 7.5% of the entrapped drug in simulated intestinal fluid (SIF, pH 7.2) and 33% in simulated body fluid (SBF, pH 7.2) for 72 h. The material SBA@N presented an initial burst release of 13% in simulated intestinal fluid and 32.6% in simulated gastric fluid (SGF, pH 1.2), while about 70% of the drug was released within the next 72 h. Density functional theory (DFT) calculations have also supported the slow drug release from the SBA@3N material. The release mechanism of the drug from the prepared carriers was studied by first-order, second-order, Korsmeyer–Peppas, Hixson–Crowell, and Higuchi kinetic models. The drug release from these carriers follows Fickian diffusion and zero-order kinetics in SGF and SBF, whereas first-order, non-Fickian diffusion, and case-II transport were observed in SIF.Discussion: Based on these findings, the proposed synthesized hybrid materials may be suggested as a potential drug delivery system for anti-cancer drugs such as 5-fluorouracil

Anticancer and Antimicrobial Activity of Silver Nanoparticles Synthesized from Pods of Acacia nilotica

Green synthesized silver nanoparticles (AgNPs) have been used against antibiotic-resistant bacteria and chemo-resistant cancer cells. We synthesized AgNPs from Acacia nilotica pods, evaluating their antibacterial activity against eight bacterial strains and anticancer efficiency against two colon cancer cell lines, SW620 and SW480. Expression levels of eight genes (β-catenin, APC, TP53, Beclin1, DKK3, Axin, Cyclin D1, and C-myc) were checked by a reverse transcription-polymerase chain reaction in cancer cells before and after treatment with A. nilotica extract and A. nilotica-AgNPs. Prepared nanoparticles were characterized through ultraviolet-visible (UV-vis), Zetasizer, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Fourier transform infrared spectroscopy (FTIR) was used to identify the functional group in extracts. At first, AgNPs were confirmed by a sharp peak of surface plasmon resonance at 375 nm. The Z-average size was 105.4 nm with a polydispersity index of 0.297. TEM showed particle size of 11–30 nm. The prepared AgNPs showed promising antibacterial activity against bacterial strains and cytotoxic activity against the cancer cell lines. Expression levels of all the genes were affected by extract and AgNPs treatment. Overall, this study recommended both A. nilotica pods and A. nilotica-AgNPs as attractive candidates for antibacterial and anticancer applications

Anticancer and Antimicrobial Activity of Silver Nanoparticles Synthesized from Pods of <i>Acacia nilotica</i>

Green synthesized silver nanoparticles (AgNPs) have been used against antibiotic-resistant bacteria and chemo-resistant cancer cells. We synthesized AgNPs from Acacia nilotica pods, evaluating their antibacterial activity against eight bacterial strains and anticancer efficiency against two colon cancer cell lines, SW620 and SW480. Expression levels of eight genes (β-catenin, APC, TP53, Beclin1, DKK3, Axin, Cyclin D1, and C-myc) were checked by a reverse transcription-polymerase chain reaction in cancer cells before and after treatment with A. nilotica extract and A. nilotica-AgNPs. Prepared nanoparticles were characterized through ultraviolet-visible (UV-vis), Zetasizer, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Fourier transform infrared spectroscopy (FTIR) was used to identify the functional group in extracts. At first, AgNPs were confirmed by a sharp peak of surface plasmon resonance at 375 nm. The Z-average size was 105.4 nm with a polydispersity index of 0.297. TEM showed particle size of 11–30 nm. The prepared AgNPs showed promising antibacterial activity against bacterial strains and cytotoxic activity against the cancer cell lines. Expression levels of all the genes were affected by extract and AgNPs treatment. Overall, this study recommended both A. nilotica pods and A. nilotica-AgNPs as attractive candidates for antibacterial and anticancer applications

Investigation of Klotho G395A and C1818T Polymorphisms and Their Association with Serum Glucose Level and Risk of Type 2 Diabetes Mellitus

Objective: The objective was to study the association of Klotho gene G395A and C1818T single nucleotide polymorphisms with glycemia, serum, glycosylated hemoglobin (HbA1c) level and the risk of type 2 diabetes mellitus (T2DM) in the Pashtun population of Pakistan. Methods: In this study, 195 normal individuals and 217 T2DM patients were enrolled. All subjects were divided into three groups, namely overall subjects (control + T2DM patients), control individuals and T2DM patients, and their fasting glucose, HbA1c level, lipid profile and C1818T and G395A polymorphisms were determined. Results: The allele frequencies of G395A in overall subjects were 0.568 for A and 0.432 for G. Similarly, allele frequencies for G395A in overall subjects were 0.597 and 0.403 for C and T alleles, respectively. The AA genotype of G395A was observed to be a risk factor for T2DM. In normal individuals, no significant (p > 0.05) association was observed between klotho C1818T and G395A polymorphisms and hyperglycemia. In overall subjects, the C1818T polymorphism was associated (p p < 0.05) associated with high fasting glucose and HbA1c levels both in males and females. Conclusion: The G395A polymorphism was observed to increase the risk of T2DM. Both C1818T and G395 were associated with high fasting glucose and HbA1c levels in T2DM patients

Prevalence and Significance of Pyuria in Chronic Kidney Disease Patients in Saudi Arabia

Chronic kidney disease (CKD) is considered a major health problem, which poses a burden for health care systems worldwide. It has been estimated that 10% of the population worldwide have CKD; however, most of the cases are undiagnosed. If left untreated, CKD could lead to kidney failure, which highlights the importance of early diagnosis and treatment. Pyuria has been reported in CKD patients, and could be the result of several comorbidities, such as diabetes, or urinary tract infections (UTIs). A few studies have shown that pyuria is associated with the late stages of CKD. However, there are limited data on the prevalence of non-UTI (sterile) and UTI–pyuria in different CKD patient populations, and its association with the decline in kidney function and progression of CKD. In this retrospective study, we report the prevalence of pyuria (sterile and UTI) in 754 CKD patients of King Fahd Specialist Hospital, Buraydah, Saudi Arabia. Our data showed that 164/754 CKD patients (21.8%) had pyuria, whereas 590 patients (78.2%) presented with no pyuria. There was a significantly higher percentage of late-stage (stage 4) CKD patients in the pyuric group compared to the non-pyuric group (36.6% vs. 11.9%). In line with the previous data, proteinuria was detected in a significantly higher percentage of pyuric patients, in addition to significantly higher levels of serum creatinine and urea, compared to non-pyuric patients. Furthermore, 13.4% of the pyuric CKD patients had UTI, whereas 86.6% presented with sterile pyuria. E. coli was indicated as the causative agent in 45.5% of UTI patients. Our patient data analysis showed that a significantly higher percentage of UTI–pyuric CKD patients, than sterile pyuric patients (63.6% vs. 19.7%), had higher numbers of urinary white blood cells (&gt;50/HPF, WBCs). The data also showed that a higher percentage of UTI–pyuric patients were late-stage CKD patients, compared to sterile pyuric patients (50% vs. 34.5%). Our findings indicate that a high level of pyuria could be considered as a marker for late-stage CKD, and that UTI is an important risk factor for the decline in kidney function and the progression to late-stage CKD. We believe that further studies are needed to correlate pyuria to kidney function, which could be helpful in monitoring the progression of CKD. Moreover, the management of comorbidities, such as diabetes and UTIs, which are risk factors for CKD and associated pyuria, could help to control the progression of CKD to the late stages

Heparin-Loaded Alginate Hydrogels: Characterization and Molecular Mechanisms of Their Angiogenic and Anti-Microbial Potential

Background: Chronic wounds continue to be a global concern that demands substantial resources from the healthcare system. The process of cutaneous wound healing is complex, involving inflammation, blood clotting, angiogenesis, migration and remodeling. In the present study, commercially available alginate wound dressings were loaded with heparin. The purpose of the study was to enhance the angiogenic potential of alginate wound dressings and analyze the antibacterial activity, biocompatibility and other relevant properties. We also aimed to conduct some molecular and gene expression studies to elaborate on the mechanisms through which heparin induces angiogenesis. Methods: The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Swelling ability was measured by soaking hydrogels in the Phosphate buffer at 37 °C, and cell studies were conducted to evaluate the cytotoxicity and biocompatibility of hydrogels in NIH3T3 (fibroblasts). Real-time PCR was conducted to check the molecular mechanisms of heparin/alginate-induced angiogenesis. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Results: FTIR confirmed the formation of heparin-loaded alginate wound dressing and the compatibility of both heparin and alginate. Among all, 10 µg/mL concentration of heparin showed the best antibacterial activity against E. coli. The swelling was considerably increased up to 1500% within 1 h. Alamar Blue assay revealed no cytotoxic effect on NIH3T3. Heparin showed good anti-microbial properties and inhibited the growth of E. coli in zones with a diameter of 18 mm. The expression analysis suggested that heparin probably exerts its pro-angiogenetic effect through VEGF and cPGE. Conclusions: We report that heparin-loaded alginate dressings are not cytotoxic and offer increased angiogenic and anti-bacterial potential. The angiogenesis is apparently taken through the VEGF pathway

Long-Term Impact of Multiple Micronutrient Supplementation on Micronutrient Status, Hemoglobin Level, and Growth in Children 24 to 59 Months of Age: A Non-Randomized Community-Based Trial from Pakistan

Cost-effective interventions are needed to address undernutrition, particularly micronutrient deficiencies, which are common in children under the age of five in low- and middle-income countries. A community-based, non-randomized clinical trial was undertaken in the Kurram district of Khyber Pakhtunkhwa from January 2018 to June 2019, to evaluate the effect of locally produced micronutrient powder (local name: Vita-Mixe) on plasma micronutrient status, hemoglobin level, and anthropometric outcomes. Children aged 24–48 months old were recruited and allocated to the intervention and control arm of the study. The enrolled children in the intervention arm received one micronutrient powder (MNP) sachet for consumption on alternate days for 12 months. To assess the impact of the intervention on plasma levels of zinc, vitamin D, vitamin A, and hemoglobin level, blood samples were taken at baseline and after one year following the intervention. The analysis was conducted using Enzyme-Linked Immunosorbent Assay (ELISA), atomic absorption spectrometry, and an automated hematology analyzer. For the impact on growth parameters, the anthropometric assessment was performed using WHO standard guidelines. A 24 h dietary recall interview was used to assess the nutrient intake adequacy. Results showed that in the intervention arm, children had on average a 7.52 ng/mL (95% CI 5.11–9.92, p-value p-value p-value p-value p p p = 0.93). In conclusion, micronutrient powder supplementation is a cost-effective intervention to improve the micronutrient status, hemoglobin level, and growth parameters in under-five children, which can be scaled up in the existing health system to address the alarming rates of undernutrition in Pakistan and other developing countries