In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer.

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability. Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C -80, C-120,C -150, C -200 ns) revealed strong hydrogen bonding in the complexes and showed -12.9, -11.6, and -11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis. Conclusion: Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

Impacts of Smoking and Stomach Disorders on Essential Elements in Biological Samples of Cement and Glass Industrial Workers.

The infection caused by Helicobacter pylori (H. pylori) disrupts the metabolism and absorption of essential trace elements. Stomach disorders are related to changes in essential trace element metabolism caused by increased toxic metal exposure and H. pylori infection. The aim of the work is to link the development of stomach-related illnesses to an imbalance of essential trace and toxic metals. We have investigated the variations in essential trace elements such zinc (Zn), iron (Fe), and copper and toxic metals like lead (Pb) and cadmium (Cd) in biological (scalp hair, blood) samples of glass and cement workers. The study participants are further divided into smokers and nonsmokers, as well as diseased (gastric ulcer, irritable bowel syndrome, and chronic ulcer) and exposed referents (non-diseased industrial workers). Biological samples of age-matched (40-60 years) male subjects living in non-industrial areas were gathered for comparative purposes. After a pre-concentration method, the drinking water of industrial and domestic areas was analysed for both toxic metals. Microwave-aided acid digestion was used to oxidise the matrices of biological samples before atomic absorption spectrometer analysis of selected metals. Toxic metal levels in both industries' drinking water were much higher than those found in domestically treated water (p < 0.01). Industrial workers suffering different types of stomach disorders have two to three times higher Pb and Cd concentrations than age-matched referents. Toxic metals are found in higher concentrations in smoker referents and diseased patients' biological samples than in nonsmoker subjects. The findings of this study suggested that Pb and Cd toxicity's immunological effects may be associated to an increased vulnerability to chronic infections.

Essential trace and toxic elemental concentrations in biological samples of male adult referent and Eunuch subjects.

BACKGROUND: The influence of essential nutrients such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) on male fertility has been extensively studied. For reproductive health, adequate spermatogenesis, sperm maturation and motility, as well as optimal sperm function, these essential elements are required. Several pathologic and male infertility disorders have been linked to an imbalance of these elements. METHODS: The purpose of this study was to determine the relationship between essential and toxic elements, such as Ca, Cu, Fe, Mg Se, and Zn, as well as cadmium (Cd), lead (Pb), and mercury (Hg) in human biological samples, such as blood, serum, and seminal plasma, from 96 referent male adults aged 21 to 49 years, who were further divided into three age groups. The biological samples of Eunuch people (n = 37), ranging in age from 21 to 42 years, were also analysed for comparison. The method of acid digestion was controlled by a microwave oven. The essential and toxic elements in the oxidised biological samples were determined using atomic absorption spectrometry. Certified reference material of blood and serum was being used to validate the methodology's accuracy. RESULT: The Ca, Cu, Fe, Mg, Se, and Zn concentrations in blood and serum samples of Eunuch people were found to be lower, whereas Cd, Pb, and Hg levels were significantly higher than those found in data from normal adult male subjects (p 0.001). The results reveal that the concentrations of Ca, Cu, Fe, Mg, Se, and Zn in the seminal plasma of adult male participants in the younger age group (21-29) were higher than those in the older age groups (30-39) and (40-49). Although essential trace element levels in Eunuch people's biological samples were significantly lower than those observed in adult male subjects. CONCLUSION: Essential elemental deficiency and elevated levels of toxic heavy metals in all biological fluid samples may have significant negative effects on human reproductive health (sperm quality and function), leading to male infertility.

Hazardous impact of organic arsenical compounds in chicken feed on different tissues of broiler chicken and manure.

The purpose of this study was to evaluate the translocation of arsenic (As) from feed to different tissues of broiler chicken (leg, breast, liver and heart) and excretory product (manure). The feed, broiler chicken and manure samples were collected from five selected poultry farms. The As concentrations in all samples were determined by electrothermal atomic absorption spectrometry, after microwave assisted acid digestion in closed vessels. The concentrations of As in different chicken feeds were found in the range of 21.3-43.7 µg g⁻¹. The contents of As in different tissues of broiler chicken, liver, muscles and heart were found in the range of 3.07-7.17, 2.15-5.28 and 2.11-6.36 µg g⁻¹, respectively, while manure samples contains 22.8-50.3 µg g⁻¹. The obtained data shows the high correlation coefficient between As contents in feed, excretory product or manure and tissues of broiler chicken in the range of r=0.41-0.83. The high level of As in excretory product may add toxicant to environment, on their disposal.

Speciation and evaluation of Arsenic in surface water and groundwater samples: a multivariate case study.

The principal object of the current study was to estimate total arsenic and its inorganic speciation in different origins of surface water (n=480) and groundwater (n=240) of Sindh, Pakistan. This study provided a description based on the evaluation of physico-chemical parameters of collected water samples and possible distribution of As with respect to its speciation. The concentration of total inorganic As (iAs) and its species (As(3+) and As(5+)) for the surface and underground water was reported in terms of basic statistical parameters, principal component analysis, cluster analysis, metal-to-metal correlations and linear regression analyses. The chemical correlations were observed by PCA, which were used to classify the samples by CA, based on the PCA scores. Standard addition method confirmed the accuracy; the recoveries of As(3+) and iAs were found to be >98%. The concentration of As(5+) in the water samples was calculated by the difference of the total inorganic arsenic and As(3+). The results revealed that the groundwater of the understudied area was more contaminated as compared to the surface water samples. The mean concentration of As(3+) and As(5+) in the surface water and groundwater samples were in the range 3.0 to 18.3 and 8.74-352 microg/L, respectively.