Repurposing of Strychnine as the Potential Inhibitors of Aldo-keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis.

AKR1B1 and AKR1B10 are important members of aldo-keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism. These enzymes are involved in various metabolic processes, including the synthesis and metabolism of hormones, detoxification of reactive aldehydes, and the reduction of various endogenous and exogenous compounds. This study aimed to explore the potential of strychnine as an anticancer agent by targeting AKR1B1 and AKR1B10 via drug repurposing approach. To assess the drug-like properties of strychnine, a physiologically based pharmacokinetic (PKPB) model and High Throughput Pharmacokinetics (HTPK) approach were employed. The obtained results fell within the expected range for drug molecules, confirming its suitability for further investigation. Additionally, density functional theory (DFT) studies were conducted to gain insight into the electronic properties contributing to the drug molecule's reactivity. Building upon the promising DFT results, molecular docking analysis using the AutoDock tool was performed to examine the binding interactions between strychnine and the proposed targets, AKR1B1 and AKR1B10. Findings from the molecular docking studies suggested a higher probability of strychnine acting as an inhibitor of AKR1B1 and AKR1B10 with docking scores of - 30.84 and - 29.36 kJ/mol respectively. To validate the stability of the protein-ligand complex, Molecular Dynamic Simulation (MDS) studies were conducted, revealing the formation of a stable complex between the enzymes and strychnine. This comprehensive approach sheds light on the potential effectiveness of strychnine as a treatment for breast, lung, liver, and pancreatic cancers, as well as related malignancies. The novel insights gained from the physiologically based pharmacokinetic modeling, density functional theory, molecular docking, and molecular dynamics simulations collectively support the prospect of strychnine as a promising molecule for anticancer therapy. Further investigations are warranted to validate these findings and explore the therapeutic potential of strychnine in preclinical and clinical settings.

Experimental investigations of arsenic adsorption from contaminated water using chemically activated hematite (Fe2O3) iron ore.

Indigenous hematite iron ore was chemically activated as a function of various hydrogen peroxide concentrations (0.5, 1, 1.5, and 2.0 M), activation time, and iron ore size. Adsorption potential was evaluated at various initial arsenic concentrations, contact time, adsorbent dose, and particle size. Maximum 95% removal efficiency was achieved at 600-µm size of iron ore, activated with 0.5 M concentration of hydrogen peroxide at 24 h of activation time. The experimental data were further evaluated through Langmuir and Freundlich isotherms. The maximum 14.46 mg/g of adsorption capacity was observed through Langmuir isotherm. Moreover, adsorption kinetics was evaluated using pseudo-first-order and pseudo-second-order kinetics, and the intra-particle diffusion model. The kinetics of arsenic adsorption was best described by using the pseudo-first-order kinetics with a kinetic rate of 0.621 min-1. The hematite iron ore before and after arsenic adsorption was characterized by XRD, SEM, and EDX.

Laser induced breakdown optical emission spectroscopic study of silicon plasma.

The laser induced breakdown optical emission spectroscopy technique has been employed for the analysis of silicon sample in the atmospheric air. Laser irradiance of 1 × 1011 Wcm-2 was created on specimen of silicon sample surface to generate the plasma plume by using the fundamental of Nd:YAG laser pulse. This laser produced silicon plasma was captured through the LIBS 2000 Spectrometer for the subsequent analysis of silicon sample. The electron temperature of silicon plasma is estimated to be 7500 K to 4000 K while electron number density of silicon plasma lies 3.2 × 1017 to 1.8 × 1017. In spatially resolved laser induced plasma and this temperature of silicon plasma has been estimated from the Boltzmann plot method to be in local thermodynamic equilibrium, and electron number density of silicon plasma has been estimated from the Stark width broadening at λ ~ 288.1 nm respectively. Observed result in spatially resolved laser plasma which shows the recombination rate of plasma plume along the direction of expansion. Which also affects on the temperature and density of silicon plasma besides the intensity decreasing factor with distance in silicon ionic and neutrals transition lines is discussed.

Lead Assessment in Biological Samples of Children with Different Gastrointestinal Disorders.

Lead (Pb) levels have been evaluated in the biological samples of children with different gastrointestinal disorders. Blood, scalp hair, and urine samples of children (of age 4-10 years) complaining about different gastrointestinal disorders were analyzed. For comparison, age matched healthy subjects were also included in this study. Biological samples were digested in a microwave oven prior to Pb determination by graphite furnace atomic absorption spectrometry. Significant differences in Pb profile were found between the diseased and referent children. Elevated Pb contents were observed in case of diseased children than WHO permissible limit, while normal results were obtained for healthy referents. The results were compared with those of healthy children having the same age, socioeconomic status, and residential areas.

Evaluation of zinc, copper and iron in biological samples (scalp hair, blood and urine) of tuberculosis and diarrhea male human immunodeficiency virus patients.

BACKGROUND: The consequence of a deficiency in trace elements has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. This study examined the association between low scalp hair and blood zinc, copper, and iron concentrations and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). METHODS: The study was performed on sixty two male HIV+ patients (HIV-1) from different cities in Pakistan. The patients were divided in two groups according to secondary infections (tuberculosis, diarrhea and high fever). The biological samples (scalp hair, blood, and urine) were collected from AIDS patients. For comparative study, 120 healthy subjects (males) of the same age group (31 - 45 years), socio-economic status, localities, and dietary habits were also included. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked using certified reference materials (CRMs) and values obtained by conventional wet acid digestion method of the same CRMs. RESULTS: The results indicated significantly lower levels of Fe and Zn and high levels of Cu in the biological samples (blood and scalp hair) of male HIV-1 patients compared with control subjects. It was observed that the low levels of zinc and iron may be predictors for secondary infections in HIV-1 patients. There was a significant decrease in mean values of Fe and Zn in whole blood and scalp hair samples of three groups of AIDS patients as compared to a control healthy male group (p < 0.001). CONCLUSIONS: Deficiency of Zn and Fe might play a role in the development of AIDS in the subjects of this study.

Effects of selenium supplementation on iodine and thyroid hormone status in a selected population with goitre in Pakistan.

BACKGROUND: Selenium (Se) has an essential role in thyroid hormone metabolism. It has the potential to play a major part in the outcome of iodine (I) deficiency The aim of the present study was to evaluate the Se and I status of biological samples (serum and urine) of 160 goitrous male (GMPs) and 195 female patients (GFPs). The supplemental effects of Se (200 microg/day) and I (100 - 125 microg/day) were evaluated after 6 months. For comparison purposes, non-goitrous subjects of both genders (n = 440) with same age group and socioeconomic status were also selected. METHODS: Hydride generation atomic absorption spectrometry (HGAAS) was used to investigate the Se concentration in the biological samples, prior to microwave assisted acid digestion. Quality control for the methodology was established by comparing the results obtained with certified samples with those obtained by conventional wet acid digestion method on the same CRMs and real samples. RESULTS: The mean serum Se concentration was significantly lower, while urinary Se was higher in GMPs and GFPs as compared to control subjects (p < 0.005 and < 0.007, respectively). The levels of I, free tri-iodothyronine, and thyroxin were found in goitrous patients of both genders were low compared to age matched healthy controls (p < 0.015, < 0.006, and < 0.002, respectively). On the other hand, high levels of thyroid stimulating hormone were observed in GMPs and GFPs (p < 0.009). CONCLUSIONS: It was observed that Se in biological samples of hypothyroid patients can play an important role in determining the severity of the hypothyroidism associated with iodine deficiency. A wide-scale epidemiological study is recommended together with the examination of the potential preventive role of Se supplementation in endemic goiter regions.

Evaluation of status of calcium, magnesium, potassium, and sodium levels in biological samples in children of different age groups with normal vision and night blindness.

BACKGROUND: The most common cause of blindness in developing countries is vitamin A deficiency. The World Health Organization (WHO) estimates 13.8 million children have some degree of visual loss related to vitamin A deficiency. The causes of night blindness in children are multifactorial and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence biological sample composition. Vitamin and mineral deficiency prevents more than two billion people from achieving their full intellectual and physical potential. METHODS: This study was designed to compare the levels of magnesium (Mg), calcium (Ca), potassium (K), and sodium (Na) in scalp hair, serum, blood, and urine of night blindness children in two age groups, (1-5) and (6-10) years, of both genders comparing them to sex- and age-matched controls. A microwave assisted wet acid digestion procedure was developed as a sample pretreatment for the determination of Mg, Ca, K, and Na in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, serum, blood, and urine. The digests of all biological samples were analysed for Mg, Ca, K, and Na by flame atomic absorption spectrometry (FAAS) using an air/acetylene flame. RESULTS: The results indicated significantly lower levels of Mg, Ca, and K in the biological samples (blood, serum, and scalp hair) of male and female children with night blindness and higher values of Na compared with control subjects of both genders. CONCLUSIONS: These data present guidance to clinicians and other professionals investigating deficiency of essential mineral elements in biological samples (scalp hair, serum, and blood) of children with night blindness.

Evaluation of calcium, magnesium, potassium, and sodium in biological samples of Pakistani viral hepatitis (A-E) patients and controls.

BACKGROUND: The aim of the present study was to compare the level of calcium (Ca), magnesium (Mg), potassium (K), and sodium (Na) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different types of viral hepatitis (A, B, C, D, and E; n = 521) of both genders, ages ranged between 31-45 years. For comparative study, 255 age-matched subjects of both genders, residing in the same city, were selected as controls. METHOD: The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and values obtained by conventional wet acid digestion method on the same CRMs. RESULT: The results of this study showed that the mean value of Na was higher in blood, sera, and scalp hair samples of hepatitis patients, while Ca, Mg and K levels were found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). CONCLUSIONS: These results are consistent with data reported in literature, confirming that the deficiency of essential mineral elements and sodium overload can directly cause lipid peroxidation and eventually hepatic damage.

Case-control study of male cancer patients exposed to arsenic-contaminated drinking water and tobacco smoke with relation to non-exposed cancer patients.

The investigated data indicated that inorganic arsenic in drinking water is associated with increased mortality from different types of cancers. In the present study, biological samples (blood and scalp hair) of male subjects having lung and bladder cancers and non-cancerous subjects belonging to arsenic (As)-exposed area of southern parts of Pakistan were analysed for As contents. The As levels in drinking water of understudy area showed that sections of understudy population are exposed to arsenic concentrations, which was 3-15-fold higher than the permissible level (<10 µg/L). For comparative purposes the biological samples of matched male cancer patient, as referent patients belonging to big city (Hyderabad) who had used municipal treated water with low arsenic levels <10 µg/L, were also collected. The exposed cancer patients have 2-3-fold higher level of As in both biological samples compared to non-exposed case-matched cancerous male subjects. This study is compelling evidence in support of positive associations between arsenic-contaminated water, food and cigarette with different types of risks of cancer.

Evaluation of zinc in scalp hair and blood samples of tuberculosis and diarrhea male human immunodeficiency virus patients.

BACKGROUND: The consequence of zinc (Zn) deficiency has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. METHODS: This study examined the association between low scalp hair and blood Zn concentrations and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). The study was performed on sixty two male HIV+ patients (HIV-1) from different cities in Pakistan. The patients were divided in two groups according to secondary infections (tuberculosis, diarrhea, and high fever). The biological samples (scalp hair and blood) were collected from AIDS patients, and for comparative study, 120 healthy subjects (males) of same age group (31 - 45 years), socio-economic status, localities, and dietary habits were also included. RESULTS: The Zn in biological samples was determined by flame atomic absorption spectrometry prior to microwave assisted acid digestion. The proposed method was validated by a certified sample of human hair BCR 397 and Clincheck control-lyophilized human whole blood. It was observed that the low levels of Zn may be predictors for secondary infections in HIV-1 patients. There was a significant decrease in mean values of Zn in whole blood and scalp hair samples in both groups of AIDS patients as compared to a controlled healthy male group (p < 0.001). CONCLUSIONS: Deficiency of zinc might play a role in the development of AIDS in the subjects of this study.

Determination of arsenic in scalp hair samples from exposed subjects using microwave-assisted digestion with and without enrichment based on cloud point extraction by electrothermal atomic absorption spectrometry.

A simple and rapid cloud point extraction (CPE) procedure was applied for preconcentration of trace quantities of arsenic (As) in scalp hair samples. The samples were subjected to microwave-assisted digestion in a mixture of nitric acid and hydrogen peroxide (2 + 1, v/v) prior to preconcentration by CPE. The As in digested samples was complexed with ammonium pyrrolidine dithiocarbamate (APDC), and the resultant As-PDC complex was extracted by a nonionic surfactant, octylphenoxypolyethoxyethanol (Triton X-114). After centrifugation, the surfactant-rich phase was diluted with 0.1 M HNO3 in methanol and analyzed by electrothermal atomic absorption spectrometry. The experimental parameters, i.e., amount of APDC, concentration of Triton X-114, equilibrium temperature and time, were optimized. For validation of the proposed method, a certified reference material (CRM) of human hair (BCR 397) was used. No significant difference (P > 0.05) was observed between the experimental results and certified values of the CRM (paired t-test). The LOD and LOQ obtained under the optimal conditions were 0.025 and 0.083 microg/kg, respectively. The developed method was applied for the determination of As in scalp hair samples from male and female subjects of two villages of Khairpur Mir's, Pakistan.

Comparative study of liver cancer patients in arsenic exposed and non-exposed areas of Pakistan.

The investigated data shows that arsenic (As) in drinking water is associated with increased mortality from different types of cancers including liver cancer. In this study, blood and scalp hair samples of male liver cancer patients and healthy referents belonging to As exposed areas of Sindh Pakistan were analyzed for As contents. The As levels in drinking water of understudy area showed that sections of this population was exposed to 3-15-folds higher concentrations of As than permissible limit. For comparative purposes, blood and scalp hair samples of matched cancerous patient as referent patients belonging to big city (Hyderabad) who have used municipal treated water with low As levels <10 µg/L were also collected. The results of this study showed that the average As concentration was higher in the blood and scalp hair of exposed and non-exposed referent cancer patients as compared to referents (p < 001). The exposed cancerous patients have twofolds higher As level in both biological samples as related to non-exposed case matched cancerous male subjects.

Distribution of copper, iron, and zinc in biological samples (scalp hair, serum, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls.

The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n = 521) of both gender age ranged 31-45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.

Chromium and manganese levels in biological samples of normal and night blindness children of age groups (3-7) and (8-12) years.

This study was designed to compare the levels of chromium (Cr) and manganese (Mn) in scalp hair, blood, and urine of night blindness in children age ranged (3-7) and (8-12) years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure, was developed as a sample pretreatment, for the determination of Cr and Mn in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood and urine. The digests of all biological samples were analyzed for Cr and Mn by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cr, whilst low level of Mn in the biological samples (blood and scalp hair) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating deficiency of Mn and excessive level of Cr in biological samples (scalp hair and blood) of night blindness children.

Evaluation of essential trace and toxic elements in biological samples of normal and night blindness children of age groups 3-7 and 8-12 years.

The most common cause of blindness in developing countries is vitamin A deficiency. The World Health Organization estimates 13.8 million children to have some degree of visual loss related to vitamin A deficiency. The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence biological samples composition. Vitamin and mineral deficiency prevents more than two billion people from achieving their full intellectual and physical potential. This study was designed to compare the levels of Zn, Mg, Ca, K, Na, As, Cd, and Pb in scalp hair, blood, and urine of night blindness children age ranged 3-7 and 8-12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of As, Ca, Cd, K, Pb, Mg, Na, and Zn in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The results of this study showed that the mean values of As, Cd, Na, and Pb were significantly higher in scalp hair, blood, and urine samples of male and female night blindness children than in referents (p < 0.001), whereas the concentrations of Zn, Ca, K, and Mg were lower in the scalp hair and blood but higher in the urine samples of night blindness children. These data present guidance to clinicians and other professional investigating deficiency of essential mineral elements in biological samples (scalp hair and blood) of night blindness children.

Status of toxic metals in biological samples of diabetic mothers and their neonates.

The mechanism of transport of trace elements from the mother to the newborn is still not well known. The aim of present study was to compare the status of trace toxic elements, arsenic (As), cadmium (Cd), and lead (Pb) in biological samples (whole blood, urine and scalp hair) of insulin-dependent diabetic mothers (age ranged 30-40) and their newly born infants (n = 76). An age and socioeconomics matched 68 nondiabetic mothers and their infants, residing in the same locality, who were selected as referents. The elemental concentrations in all three biological samples were determined by an electrothermal atomic absorption spectrometer, prior to microwave-assisted acid digestion. The mean values of As, Cd, and Pb in all biological samples of diabetic mothers and their infants were significantly higher as compared to the referent mother-infant pair samples (p < 0.01). The high levels of As, Cd, and Pb in biological samples of diabetic women may play a role in the pathogenesis of diabetes mellitus and impacts on their neonates.

Interactions between cadmium and zinc in the biological samples of Pakistani smokers and nonsmokers cardiovascular disease patients.

The pathogenesis of some cardiovascular diseases (CVDs) has been altered with changes in the balance of certain trace and toxic elements. The aim of the present study was to assess the role of zinc (Zn) and cadmium (Cd) in smoker and nonsmoker male CVD patients (n = 457) of two age groups (31-45) and (46-60). The both elements were determined in biological samples (scalp hair, blood, and urine) of CVD patients and healthy referents for comparison purpose. The concentrations of Zn and Cd were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. It was observed that the mean values of Cd were significantly higher in the biological samples of smokers CVD as compared to nonsmoker CVD patients, while the level of Zn was lower in both smoker and nonsmoker patients. The concentrations of Zn in whole blood and scalp hair samples were lower in CVD patients as compared to referents (p > 0.001). Results showed significant changes of levels of Cd and Zn in blood and scalp hair samples of CVD patients when compared with healthy referents, while reverse in the case of urine samples. It was observed that low Zn levels were associated with both smoker and nonsmoker CVD patients, while increased cadmium accumulation was observed in smoker patients as compared to nonsmoker patients (p > 0.025).

Association of environmental toxic elements in biological samples of myocardial infarction patients at different stages.

The exposure of toxic elements may directly or indirectly associate with different pathogenesis of heart diseases. In the present study, the association of arsenic (As), cadmium (Cd), cobalt (Co), lead (Pb), and nickel (Ni) in biological samples (whole blood and urine) and mortality from myocardial infarction (MI) patients at first, second, and third heart attacks was carried out. Both biological samples of 130 MI patients (77 male and 53 female), with ages ranging from 45 to 60 years, and 61 healthy persons (33 male and 28 female) of the same age group were collected. The elements in biological samples were assessed by electrothermal atomic absorption spectrophotometer, prior to microwave-assisted acid digestion. The validity of methodology was checked by the biological certified reference materials. During this study, 78% of 32 patients aged above 50 years, registered after third MI attack, died. In these subjects, the levels of As, Cd, Co, Ni, and Pb in blood samples were higher in MI patients as compared with referents (p < 0.05), while increased by 11.7%, 12.2%, 5.55%, and 7.2%, respectively, in the blood samples of those patients who tolerated the third MI attack (p = 0.12). The high level of understudied toxic elements may play a role in the mortality of MI patients.

Evaluation of status of cadmium, lead, and nickel levels in biological samples of normal and night blindness children of age groups 3-7 and 8-12 years.

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood trace metals toxicity, which is the most common problem found in underdeveloped countries. This study was designed to compare the levels of cadmium (Cd), lead (Pb), and nickel (Ni) in scalp hair, blood, and urine of night blindness children age ranged 3-7 and 8-12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of Cd, Pb, and Ni in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cd, Pb, and Ni by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cd, Pb, and Ni in the biological samples (blood, scalp hair, and urine) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating toxicity of trace metals in biological samples of night blindness children.

Evaluation of cadmium, chromium, nickel, and zinc in biological samples of psoriasis patients living in Pakistani cement factory area.

Psoriasis is a noncontiguous common and chronic skin disorder. The aim of the present study was to compare the level of trace elements cadmium (Cd), chromium (Cr), Nickel (Ni), and zinc (Zn) in biological samples (whole blood, urine, and scalp hair) of psoriasis patients of both gender age ranged (25-55 years) at mild, moderate severe, and more severe stage (n = 418) living in the vicinity of cement factory. For comparison purposes, healthy age-matched referent subjects, residents of industrial and non-industrial area, of both gender were also selected (n = 241). The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The validity and accuracy of methodology was checked by using certified reference materials (CRMs) and conventional wet acid digestion method on same CRMs and real samples. The results of this study showed that the mean values of Cd, Cr, Ni, and Pb were significantly higher in scalp hair, blood, and urine samples of mild and severe psoriasis patients as compared to referents (p < 0.001), while the concentration of Zn was lower in the scalp hair and blood, but higher in the urine samples of psoriasis patients. The deficiency of Zn in psoriasis patients may be undoubtedly caused by the toxic element exposures via cement factory.