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Spreading infectious illnesses such as viral meningitis, hepatitis, and cytomegalovirus among people is facilitated by spitting in public. India is more prone to transferring infectious illnesses. Recent research discovered that the new Coronavirus may also be transmitted via an infected person’s saliva. Self-collected saliva from 91.7% of patients contains COVID-19. Numerous nations have prioritized preventing individuals from spitting in open or public areas such as hospitals, parks, airports, train stations, etc. The UVC range has a greater damaging effect on microbial cells because microorganisms’ intracellular components, such as RNA, DNA, and proteins, are sensitive to UVC photon absorption. In this article, the design and construction of a solar-concentrating spittoon is attempted. At its receiver, it can create a temperature of 390 K and 176 W of heat. At this temperature, most viruses (including Coronavirus), bacteria, and pathogens are inactivated. Daily, from 8:00 a.m. until 5:00 p.m., the solar-concentrating spittoon is functional. The solar-concentrating spittoon performance was best for nine hours. The receiver thermal efficiency was 80% and 20% of heat was lost to the surroundings. The overall efficiency was found to be 70%. During this time, most people spend their time outside, where this solar-powered spittoon can incinerate human cough and spit within one minute. The installation of this solar-concentrated spittoon will aid in preventing the spread of fatal dangerous diseases and cleaning the city.

Through the boost of the natural medicinal market, individuals began to use a variety of organic materials in the marketed herbal preparation. Lagerstroemia speciosa (LS) leaves are known as banaba. People have been using a decoction of LS leaves as antidiabetic. The study aimed to investigate the acute and sub-acute oral toxicity of LS in Sprague-Dawley rats. The acute toxicity was determined by a single oral dose of LS (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The LS (200 mg/kg) was given for 28 days daily in the sub-acute study. The body weight, organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied. The findings of this study showed no mortality or morbidity was found in acute and sub-acute toxicity studies in rats. Additionally, no significant variations were found in the respective weight of organ, haematological and biochemical parameters of treated groups with reference to the control group. Moreover, no visible histological changes were detected in the liver of treated groups with reference to the control. In conclusion, the oral administration of LS did not fabricate any major toxic effect in rats. No toxic consequences were reported during acute and sub-acute toxicity investigations. Overall, LS is a safe, natural bio-actives as studied. Further investigations of cytotoxicity and genotoxicity of the above drug(s) or their combinations may be executed for appreciative safety.

Hyperglycemia as a common metabolic disorder in diabetes led to oxidative stress, inflammation and other complications. Natural and manufactured antioxidants alleviates the side effects of diabetes. The purpose of current study is to investigate the effect of pyrroloquinoline quinine (PQQ) as an antioxidant on the content of glucose-induced oxidative stress generation in the cells of the human hepatocellular liver carcinoma (HepG2) by inhibiting advanced glycation end products (AGEs) formation. The HepG2 cells were exposed to high dose (50 mM) of glucose (HG) only and with PQQ (HG + PQQ). Treatment with high dose increased AGEs formation, expression of receptor for advanced glycation endproducts (RAGE), reactive oxygen species ROS production, and oxidative stress markers in treated HepG2 cells. Interestingly, PQQ significantly reduced AGEs formation and (RAGE) expression, ROS formation, and inflammation induced by glucose. In conclusion, PQQ has a potentiail role as an antioxidant to reduce the oxidative damage during hyperglycemia by AGEs inhibition.

Islet amyloid polypeptide (amylin), consecrated by the pancreatic β-cells with insulin, has a significant role to play in maintaining homeostasis of islet cell hormones. Alzheimer's disease is the predominant source of dementia. However, its etiology remains uncertain; it appears that type 2 diabetes mellitus and other prediabetic states of insulin resistance contribute to the intermittent Alzheimer's disease presence. Amylin is abnormally elevated in Type II diabetes patients, accumulated into amylin aggregates, and ultimately causes apoptosis of the β-cells, and till date, its mechanism remains unclear. Several flavonoids have inhibitory effects on amylin amyloidosis, but its inhibition mechanisms are unknown. Screening a collection of traditional compounds revealed the flavone Chrysin, a potential lead compound. Chrysin inhibits amyloid aggregate formation according to Thioflavin T binding, turbidimetry assay. We report results of molecular interaction analysis of Chrysin with amylin which shows potent binding affinity against amylin. Pharmacokinetics and Drug likeness studies of Chrysin also suggest that it is a potential lead compound. Therefore, Chrysin prevented amylin aggregation.

The World Health Organization (WHO) recognized a novel coronavirus as the causative agent of a new form of pneumonia. It was subsequently named COVID-19 and reported as the source of a respiratory disease occurrence starting in December 2019 in Wuhan, Hubei Province, China. It has been affirmed a public health emergency of international significance by the World Health Organization. It is regarded as a subset of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS); COVID-19 is triggered by a betacoronavirus called SARS-CoV-2, which affects the lower respiratory tract and occurs in humans as pneumonia. A variety of drugs, such as remdesivir and favipiravir, are currently undergoing clinical trials to evaluate for the management of COVID-19. The effect of the pandemic as well as the epidemic that follows through the life cycles of various recycled plastic is evaluated, particularly those required for personal safety and health care. In response to the growth in COVID-19 cases worldwide, the energy and environmental impacts of these lifecycle management have risen rapidly. However, significant hazardous waste management concerns arise due to the need to assure the elimination of residual pathogens in household and medical wastes. This review article summarizes the preventive and environmental management of COVID-19.

This trial assessed the efficacy of a commercial essential oil (EO) product on the immune response to vaccination against Newcastle disease (ND) and subsequent challenge with virulent ND virus genotype VII (vNDv genotype VII) by using the following experimental groups of broiler chickens (Each group had 21 birds with 3 replicates in each, n = 7): NC (negative control), PC (positive control), VC (vaccinated), and VTC (vaccinated and treated with EOs). Moreover, in a trial to study the effect of EOs on vNDv genotype VII in vivo as a preventive or therapeutic measure, 2 additional ND-vaccinated groups were used (PRV: medicated 1 D before vNDv challenge for 5 D; and TTT: medicated 2 D after vNDv challenge for 5 D). In addition, the immune-modulatory effect of EOs on the avian influenza (AI), infectious bronchitis (IB), and infectious bursal disease (IBD) vaccines was assessed through the serological response. The use of EOs along with administration of ND vaccines (VTC) revealed a lower mortality rate (42.86%), clinical signs, and postmortem lesion score (11) than ND vaccines alone (VC) (52.28% mortality and score 15), in addition to lower hemagglutination inhibition (P < 0.05) (6.5 ± 0.46) and viral shedding (10 log 2.28 ± 0.24) titres 1 wk after challenge in comparison with VC (8.63 ± 0.65 and 10 log 3.29 ± 0.72, respectively). Nevertheless, the EOs mixture (VTC) (1952 ± 28.82) did not significantly (P > 0.05) improve growth performance compared with the nontreated birds (NC and VC) (1970 ± 19.56 and 1904 ± 38.66). EOs showed an antiviral effect on vNDv in vivo (in chickens) as a preventive measure (PRV) as well as some therapeutic effect (TTT) through decreasing the viral shedding titres (loNC0), mortality rate, and severity of clinical signs and postmortem lesions, in addition to serum malondialdhyde level. Regarding the other viruses, the EOs mixture did not improve the immune response to the AI and IB vaccines but significantly (P < 0.05) increased the ELISA antibody titre for IBD virus at the 28th D of age (2,108 ± 341.05). The studied EOs mixture showed an immune-stimulating response to ND and IBD vaccines, antiviral effect against ND virus, especially if administered before the challenge; however, it did not have a growth-promoting effect.

Diabetes mellitus is amongst the most severe incurable diseases affecting a huge number of people everywhere in the world. Diabetic nephropathy (DN) is the main cause for kidney disease, possibly due to the lack of appropriate DN treatments. The current study is to assess the role of Lagerstroemia speciosa extract (LSE) in the mitigation of DN in a streptozotocin rat model of hyperlipidemia and hyperglycemia. The animal model of DN was induced in Sprague Dawley rats by administering streptozotocin and fed on a western diet for six weeks. The administration of LSE treatment at a dose of 400 mg/kg for six weeks. LSE showed a significant decline in enhanced biochemical parameters, for instance, glucose level, creatinine, and lipid profile. LSE treatment lowered the enhanced albumin level. The advanced glycation end-product level in kidneys was significantly reduced along with augmentation in the glutathione level and a decrease in lipid peroxidation. The inflammatory markers were also reduced considerably. Thus, LSE treatment effectively protects against streptozotocin-induced nephrotoxicity in rats. LSE might act as a possible adjuvant for DN therapy and needs to be investigated further.

Cancer is the most serious disease globally and it’s the second in mortality rate after heart failure. Hepatic cancer is a common cancer disease worldwide. This investigation was designed to assess the cytotoxic and apoptotic effects of Ammi visnaga (A. visnaga) seed extract on human liver cancer cell line (HuH-7). Based on IC50 values, three doses (500, 1000, 1500 μg/ml) were selected. Treated cells with MTT assay reduced cell viability at 1000 μg/ml and higher after 48hrs. NRU test demonstrated significant increase at (1500 and 2000 μg/ml) in dose-dependent manner indicating lysosomal toxicity. The level of oxidative stress-mediated cytotoxicity was assessed using SOD, glutathione (GSH), catalase and ROS assays. The intracellular ROS was highly increased and loss of mitochondrial membrane potential (MMP) confirmed the damage of mitochondrial membrane in HuH-7 cells. The level of GSH significantly increased after treatment. In contrast, the levels of SOD, and catalase activities significantly decreased after treatment. The effects of MMP significantly decreased after treatment compared to control. Gene expression data reported significantly upregulation of apoptotic genes. In conclusion, this finding revealed that A. visnaga seeds extract has hepatoprotective potential against HuH-7 cells, signifying their promising clinical applications as a potential therapeutic agent for liver diseases.

The current study was carried out to evaluate the ameliorative effect of fucoidan against aflatoxicosis-induced hepatorenal toxicity in streptozotocin-induced diabetic rats. Sixty-four Wister albino male rats were randomly assigned into eight groups (8 rats each) that received normal saline, fucoidan (FUC) at 100 mg/kg/day orally for 4 weeks, streptozotocin (STZ) at 50 mg/kg/i.p. single dose, STZ plus FUC, aflatoxin B1(AFB1) at 50 μg/kg/i.p. after one month of the beginning of the experiment for 2 weeks, AFB1plus FUC, STZ plus AFB1, or STZ plus AFB1and FUC. Injection of rats with STZ induced hyperglycemia. Rats with STZ-induced diabetes, with or without AFB1intoxication, had significantly elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of serum urea, creatinine, cholesterol, 8-oxo-2′-deoxyguanosine, interleukin-1β, interleukin-6, and tumor necrosis factor-α. In addition, these rats exhibited increased lipid peroxidation and reduced glutathione concentration and activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes in the hepatic and renal tissues. In contrast, administration of FUC to diabetic rats, with or without AFB1intoxication, ameliorated the altered serum parameters, reduced oxidative stress, DNA damage, and inflammatory biomarkers, and enhanced the antioxidant defense system in the hepatic and renal tissues. These results indicated that FUC ameliorated diabetes and AFB1-induced hepatorenal injuries through alleviating oxidative stress, DNA damage, and inflammation.

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

The purpose of this study was to detect the immunomodulatory activity of Indigofera coerulea on the cytokine's expression in the THP-1 human cell line. THP-1 cell lines were differentiated into real macrophages. Cell's viability was assessed by MTT assay. The qRT-PCR assay was used to determine the effects of the I. coerulea extract on mRNA expression levels in THP-1 cells. The effects of extracts on proteins production were analyzed by Western blot assay and protein array. The ELISA was used to determine the effect of the plant extract on cytokine expression. Finally, apoptosis, phagocytosis, and cell migration assays were performed to investigate the effects of the extract on macrophage functions. The obtained results illustrated that I. coerulea extract possesses anti-oxidant and anti-inflammatory activities. In addition, current study reported that I. coerulea extract significantly reduced the proliferation of THP-1 cells at all-time points. Moreover, I. coerulea extract showed significant immunomodulatory activity compared with control macrophages by influencing tumor necrosis factor-α (TNF-α), IL-1β, IL-6, CCL22, CXCL10/IP-10, CXCL8/IL-8, ERK5, BAX, BcL2, Cyclin D1, ERK1, P-IκB-α, P-NF-κB, and P-p38 proteins and the signaling pathways of NF-κB, p38 MAPK, ERK1/2, and IL-6/JAK/STAT3. In conclusion, this study is the first to underline the anti-proliferative, anti-inflammatory, anti-phagocytic, anti-apoptotic, and anti-migratory properties of the studied plant extract in human monocytic THP-1 cells.

Despite recent advancements in cisplatin (cis-diamminedichloroplatinum II) and other platinum-based chemotherapeutic drugs for treating solid tumors, their uses are limited by either in terms of toxicity and/or acquired drug resistance. These side effects have a dangerous problem with higher dose for severe patients. To overcome the low therapeutic ratio of the free drug, a polymeric nanoparticle drug delivery system has been explored promoting delivery of cisplatin to tumors. Recently, the applications of nanoparticles (NPs) have been underlined for encouraging the effects of chemotherapeutic drugs in cancerous cells. The intention of this project is to assess the potential of poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for enhancing the effects of anticancer drug cisplatin. For the purpose, we have synthesized PLGA-cisplatin nanoparticles for increasing its bioavailability and studied the comparative cytotoxicity of free cisplatin and PLGA-cisplatin against MCF-7 cancer cell lines and HEK-293 normal cell lines. We have also analyzed the hallmarks of PLGA-cisplatin-induced apoptosis. The outcomes of this study may provide the possibility of delivery of anticancer drug to their specific site, which could minimize toxicity and optimize the drug efficacy.

Objectives: Nucleotide oligomerization domain 2 (NOD2) and myeloid differentiation protein 2 (MD-2) have crucial roles in the innate immune system. NOD2 is a member of the NOD-like receptor (NLR) family of pattern recognition receptors (PRRs), while MD-2 is a co-receptor for Toll-like receptor 4 (TLR4), which comprises another group of PRRs. Genetic variations in the NOD2 and MD-2 genes may be susceptibility factors to viral pathogens including hepatitis B virus (HBV). We investigated whether polymorphisms at NOD2 (rs2066845 and rs2066844) or at MD-2 (rs6472812 and rs11466004) were associated with susceptibility to HBV infection and advancement to related liver complications in a Saudi Arabian population. Methods: A total of 786 HBV-infected patients and 600 healthy uninfected controls were analyzed in the present study. HBV-infected patients were categorized into three groups based on the clinical stage of the infection: inactive HBV carriers, active HBV carriers, and patients with liver cirrhosis + hepatocellular carcinoma (HCC). Results: All four SNPs were significantly associated with susceptibility to HBV infection although none of the SNPs tested in NOD2 and MD-2 were significantly associated with persistence of HBV infection. We found that HBV-infected patients that were homozygous CC for rs2066845 in the NOD2 gene were at a significantly increased risk of progression to HBV-related liver complications (Odds Ratio = 7.443 and P = 0.044). Furthermore, haplotype analysis found that the rs2066844-rs2066845 C-G and T-G haplotypes at the NOD2 gene and four rs6472812-rs11466004 haplotypes (G-C, G-T, A-C, and A-T) at the MD-2 gene were significantly associated with HBV infection in the affected cohort compared to those found in our control group. Conclusion: We found that the single nucleotide polymorphisms rs2066844 and rs2066845 at NOD2 and rs6472812 and rs11466004 at MD-2 were associated with susceptibility to HBV infection in a Saudi population. Keywords: NOD2, MD-2, SNP, Hepatitis B virus, Saudi

Aflatoxicosis is one of the threats that cause severe mortalities in fish farms. The dietary functional additives are a friendly approach attributed to beneficial effects on aquatic animals. The study aimed at evaluating the impact of Spirulina platensis (SP) on the biochemical indices and antioxidative function of Nile tilapia (Oreochromis niloticus) intoxicated with aflatoxin B

Agrochemicals are one the most significant sources of environmental pollution. Cytotoxicity and genotoxicity are the serious side effects of fungicide. In the current study, I have evaluated acute cytotoxicity and genotoxicity of triphenyltin (TPT) on human hepatic carcinoma (HepG2) cells and the ameliorating effect of ascorbic acid for 24 h. In this experiment, I have exposed HepG2 cells to ascorbic acids (50, 100, and 200 μM) simultaneously and 24 h prior triphenyltin (TPT, 400 ng/ml) exposure for 24 h to determine the protective effect of ascorbic acid by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and NRU (neutral red uptake) assays. Oxidative stress, such as intracellular reactive oxygen species and glutathione levels, was measured in HepG2 cells. The intracellular reactive oxygen species was evaluated using fluorescent probe DCFDA (6-carboxy-2′,7′ dichloro-dihydrofluorescein diacetate). Apoptosis and genotoxicity effects of TPT in HepG2 cells were determined using flow cytometry and comet assay. The result of these experiments showed that the TPT compound (400 ng/ml) induced cytotoxicity, oxidative stress and apoptosis, and DNA damage in HepG2 cells.Ascorbic acid reduced cytotoxicity, oxidative stress, apoptosis, and genotoxicity induced by TPT. Thus, ascorbic acid is a potent antioxidant, and it showed a significant protective effect against toxicity induced by TPT in HepG2 cells.

Gadah AlBasher,1 Abdullah A AlKahtane,1 Saud Alarifi,1 Daoud Ali,1 Mohammed S Alessia,2 Rafa S Almeer,1 Mohamed M Abdel-Daim,3 Nouf K Al-Sultan,1 Ahmed A Al-Qahtani,4,5 Huma Ali,6 Saad Alkahtani1 1Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Biology, Science College, Al-Imam Muhammad Ibn Saud, Islamic University, Riyadh, Saudi Arabia; 3Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt; 4Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 5Department of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi Arabia; 6Department of Chemistry Maulana Azad National Institute of Technology, Bhopal, India Introduction: The communication between a substance and a cell may depend on whether the cell is normal or pathological. The disease cells and drug interaction may occasionally overcome beneficial action of the drug; subsequently, it is important to investigate the effect of the drug in both the normal and target cells. This study aimed to evaluate the methotrexate (MTX) antiproliferative effect and explore the mechanistic approach to investigate the cell death index in SKOV-3 ovarian cells during treatment with MTX. Methods: In vitro studies of SKOV-3 cells were examined by tetrazolium assay after exposure to various concentrations of MTX. Moreover, reactive oxygen species (ROS) generation, mitochondrial membrane potential, DNA damage, and AO/EtBr staining morphological analysis of necrotic/apoptotic cells were detected; cellular impairment in mitochondria and DNA was confirmed by JC-1 mitotracker/DAPI, respectively, and cell death pathway markers; bax/bcl-2 were analyzed. Results: A dose-dependent antiproliferative effect of MTX treatment was observed in SKOV-3 cells; the prominent inhibitory concentration was 40 µM of MTX (P

The current study was carried out to evaluate the ameliorative effect of fucoidan against aflatoxicosis-induced hepatorenal toxicity in streptozotocin-induced diabetic rats. Sixty-four Wister albino male rats were randomly assigned into eight groups (8 rats each) that received normal saline, fucoidan (FUC) at 100 mg/kg/day orally for 4 weeks, streptozotocin (STZ) at 50 mg/kg/i.p. single dose, STZ plus FUC, aflatoxin B1 (AFB1) at 50 μg/kg/i.p. after one month of the beginning of the experiment for 2 weeks, AFB1 plus FUC, STZ plus AFB1, or STZ plus AFB1 and FUC. Injection of rats with STZ induced hyperglycemia. Rats with STZ-induced diabetes, with or without AFB1 intoxication, had significantly elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of serum urea, creatinine, cholesterol, 8-oxo-2′-deoxyguanosine, interleukin-1β, interleukin-6, and tumor necrosis factor-α. In addition, these rats exhibited increased lipid peroxidation and reduced glutathione concentration and activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes in the hepatic and renal tissues. In contrast, administration of FUC to diabetic rats, with or without AFB1 intoxication, ameliorated the altered serum parameters, reduced oxidative stress, DNA damage, and inflammatory biomarkers, and enhanced the antioxidant defense system in the hepatic and renal tissues. These results indicated that FUC ameliorated diabetes and AFB1-induced hepatorenal injuries through alleviating oxidative stress, DNA damage, and inflammation.

Chlorpyrifos is an organophosphate pesticide whose exposure leads to inhibition of acetylcholinesterase (AChE) enzyme and induces oxidative stress, inflammation, and neurotoxicity. The current study was designed to evaluate the efficacy of carnosic acid (CA) in ameliorating CPF-induced cytotoxicity in mice brain and eye tissues. We allocated 40 male Swiss albino mice to receive DMSO 1% solution, oral CA 60 mg/kg/day bw, CPF 12 mg/kg/day bw via gastric gavage, or CPF plus CA at 30 and 60 mg/kg/day bw. Carnosic acid was administered once/day for 14 days, while CPF was administered in the last 7 days of the experiment. Biochemical analysis showed that CPF administration was associated with significant increases in the serum concentrations of interleukin-1β, IL-6, and tumor necrosis factor-α, while it was associated with significant reductions in serum AChE levels in mice. Moreover, CPF-intoxicated mice exhibited significantly higher levels of malondialdehyde and nitric oxide in the brain and eye tissues. However, they had significantly lower levels of reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase in comparison with normal controls. Pretreatment with CA at 30 and 60 mg/kg/day bw for 14 days significantly alleviated all the aforementioned CPF-induced alterations in a dose-dependent manner; more frequent restorations of the normal control ranges were observed in the higher dose group. In conclusion, CA offers a neuroprotective effect against CPF-induced oxidative stress and inflammation and should be further studied in upcoming experimental and clinical research.

Aflatoxins are a common food contaminant of global concern. Aflatoxin B1 (AFB1) intoxication is associated with serious health hazards. Recently, fucoidan (FUC) has gained much attention from pharmaceutical industry due to its promising therapeutic effects. The impacts of FUC on AFB1-induced liver and kidney injures have not been sufficiently addressed. This research was conducted to evaluate the ameliorative effect of FUC in AFB1-induced hepatorenal toxicity model in rats over 14 days. Five groups were assigned; control, FUC (200 mg/kg/day, orally), AFB1 (50 μg/kg, i.p.), and AFB1 plus a low or high dose of FUC. AFB1 induced marked hepatorenal injury elucidated by substantial alterations in biochemical tests and histological pictures. The oxidative distress instigated by AFB1 enhanced production of malondialdehyde (MDA) and nitric oxide (NO) along with reduction in the reduced-glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. DNA damage in the liver and kidney tissues has been demonstrated by overexpression of proliferating cell nuclear antigen (PCNA). Unambiguously, FUC consumption alleviates the AFB1-induced mitochondrial dysfunction, oxidative harm, and apoptosis. These ameliorated effects are proposed to be attributed to fucoidan's antioxidant and anti-apoptotic activities. Our results recommend FUC supplementation to food because it exerts both preventive and therapeutic effects against AFB1-induced toxicity.

The aquatic ecosystems are converting into the highly contaminated site due to environmental pollutants. The present study explores the oxidative stress and toxic potential of lead nitrate in freshwater snail Lymnaea luteola (L. luteola) L. The snails were exposed to an environmentally relevant concentration of lead nitrate for 24 and 96 h. Later exposure to lead nitrate (0, 10, 20 and 40 µg/mL) to the freshwater snail, the level of reactive oxygen species, malondialdehyde and nitric oxide (NO) were increased and glutathione, glutathione-S-transferase were decreased. Lead-nitrate-induced haemocyte cell death and it was observed by using Annexin-V FITC/PI through a flow cytometer. DNA damage in haemocyte cells was measured at above doses of lead-nitrate exposure for 24 and 96 h and it was compared to the untreated snail. Average tail DNA (%) and olive tail moment in single-cell gel test were increased dose and duration fashion and maximum DNA damage was measured at 96 h. These results indicate the ...

Background: Chorein, a protein encoded by VPS13A (vacuolar protein sorting-associated protein 13A), is defective in chorea acanthocytosis, a rare disease characterized by acanthocytosis of red blood cells and neuronal cell death with progressive hyperkinetic movement disorder, cognitive dysfunction, behavioral abnormalities and chronic hyperkalemia. Chorein is highly expressed in ZF rhabdomyosarcoma cells and counteracts apoptosis of those cells. Chorein is effective in part by interacting with and fostering stimulation of phosphoinositide-3-kinase (PI3K)-p85-subunit. PI3K dependent signaling includes the serum and glucocorticoid inducible kinase SGK1. The kinase activates NFκB with subsequent up-regulation of the Ca2+ channel subunit Orai1, which accomplishes store operated Ca2+ entry (SOCE). Orai1 and SOCE have been shown to confer survival of tumor cells. The present study thus explored whether chorein impacts on Orai1 expression and SOCE. Methods: In rhabdomyosarcoma cells chorein, Orai1, NFκB and SGK1 transcript levels were quantified by RT-PCR, Orai1 protein abundance by Western blotting, FACS analysis and confocal laser microscopy, [Ca2+]i utilizing Fura-2 fluorescence, and SOCE from the increase of [Ca2+]i following store depletion with extracellular Ca2+ removal and inhibition of the sarcoendoplasmatic reticular Ca2+ ATPase with thapsigargin. Results: The mRNA coding for chorein was most abundant in drug resistant, poorly differentiated human ZF rhabdomyosarcoma cells. Chorein silencing significantly decreased Orai1 transcript levels and Orai1 protein expression, as well as SGK1 and NFκB transcript levels. SOCE in ZF rhabdomyosarcoma cells was significantly blunted by chorein silencing, Orai1 inhibitor 2-APB (50 µM), SGK1 inhibitor EMD638683 (50 µM, 10 h) and NFκB inhibitor wogonin (50 µM, 24 h). Conclusion: Chorein is a stimulator of Orai1 expression and thus of store operated Ca2+ entry. The effect may involve SGK1 and NFκB.

International audience; Nephrotoxicity is a common adverse effect of treatment with cisplatin (CDDP). This study was performed to evaluate the antioxidant and nephroprotective efficacy of ceftriaxone (CTX) and vitamin E (Vit.E), alone and in combination against CDDP-induced acute renal injury. Fifty-six male albino rats were equally divided into seven groups, receiving (I) normal saline, (II) CTX (100 mg/kg, intraperitoneal [i.p] injection), (III) Vit.E (100 mg/kg orally), (IV) CDDP (5 mg/kg i.p injection), (V) CDDP plus CTX, (VI) CDDP plus Vit.E, and (VII) CDDP plus CTX in combination with Vit.E. All treatments were administered daily for 10 days except CDDP, which was given as a single dose at the sixth day of the study. Compared to normal control rats, CDDP-injected rats showed significantly (p < 0.05) higher serum levels of renal injury biomarkers (uric acid, urea, and creatinine) and tumor necrosis factor-α (TNF-α), as well as increased renal tissue concentrations of malondialdehyde, nitric oxide, and TNF-α. Moreover, CDDP administration was associated with significantly lower (p < 0.05) renal tissue levels of reduced glutathione and activities of endogenous antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and total antioxidant capacity. All these alterations were significantly ameliorated in CDDP-injected rats, receiving CTX and/or Vit.E, compared to rats receiving CDDP alone. Interestingly, the antioxidant and anti-inflammatory effects were more marked in the CTX-Vit.E combination group, compared to groups receivingeither drug alone. In conclusion, CTX and Vit.E (especially in combination) could counteract the nephrotoxic effect of CDDP, probably through their antioxidant activities.

International audience; Fucoidans (FUCs) are sulfated polysaccharides that have a wide range of bioactivities. The current study was designed toevaluate the antioxidant potential of FUC against microcystin-LR (MC-LR)-induced toxicity. Five mice groups (n = 8) wereused. Group 1 received saline, Group 2 received oral FUC 100 mg/kg/day for 21 days, Group 3 received i.p. MC-LR 10 μg/kg/day for 14 days, Group 4 received MC-LR plus FUC 50 mg/kg/day, and Group 5 received MC-LR plus FUC 100 mg/kg/day. Thepresent study showed that MC-LR administration was associated with significant increases (p < 0.01) in serum concentrations ofhepatic (aspartate transferase, alanine transferase, and alkaline phosphatase), renal (urea and creatinine), and cardiac (creatinekinase and CK-MB) injury biomarkers, as well as serum lactate dehydrogenase, cholesterol, and pro-inflammatory cytokines(interleukins-1β and 6, and tumor necrosis factor-α), compared with the control group. Further, MC-LR-intoxicated miceexhibited significantly higher (p < 0.01) hepatic, renal, and cardiac tissue levels of malondialdehyde and nitric oxide, as wellas lower tissue levels of reduced glutathione and activities of glutathione peroxidase, superoxide dismutase, and catalase enzymesin comparison with control mice. Treatment by FUC significantly ameliorated all the above-mentioned alterations in a dosedependent manner with frequent restoration of the normal ranges in the FUC 100 mg/kg/day dose group. Moreover, treatment byFUC alone at 100 mg/kg/day was not associated with significant negative alterations in the assessed biochemical parameters,highlighting its safety at this dose. In conclusion, treatment by FUC significantly ameliorated organ injury, induced by MC-LR inmouse hepatic, renal, and cardiac tissues.

Microcystin- (MC-) LR is the most frequent cyanotoxin produced byMicrocystis aeruginosacyanobacteria in the contaminated freshwater environment. MC represents a health hazard to humans and animals. Therefore, the present study was designed to evaluate the potential ameliorative effect of thymoquinone (TQ) and/or piperine (PP) against MC toxicity in mice. Fifty-six mice were randomly divided into seven experimental groups. Group I is the normal control that received distilled water for 21 days; Group II (TQ) was treated with TQ (10 mg/kg, i.p) for 21 days; Group III (PP) was treated with PP (25 mg/kg, i.p) for 21 days; Group IV (MC) was treated with MC (10 μg/kg, i.p) for 14 days and served as the toxic control; and Groups V, VI, and VII received TQ and/or PP 7 days prior to MC and continued for 14 days with MC. The results revealed that MC elicited hepatotoxicity and neurotoxicity which was evident due to the significant elevation of serum AST, ALT,γGT, ALP, LDH, IL-1β, IL-6, and TNF-αlevels. Furthermore, MC markedly increased MDA and NO contents along with reduction of GSH, SOD, CAT, and GSH-Px in liver and brain tissues. The electron transport chain may be a possible target for MC. TQ and/or PP ameliorated the MC-mediated oxidative damage in the liver and brain which might be attributed to their antioxidant properties. However, the concurrent treatment of TQ and PP showed the best regimen as a result of the PP-enhanced bioavailability of TQ.

International audience; Heat stress (HS) has adverse effects on the body: it decreases body weight, feed efficiency, feed intake, carcassquality, and nutrient digestibility. Chromium (Cr) can prevent lipid peroxidation induced by HS through itsstrong antioxidant activities, especially when it is added to the poultry diet. It improves the action of insulinand nutrient metabolism (of lipids, proteins, nucleic acid, and carbohydrates) through activation of enzymes associated with such pathways. The results of the studies on Cr added to diets with concentrations of 0.05 mg Cr/kgof Cr-methionine led to improved feed efficiency and DM intake by cows and Holstein dairy calves exposed tohigh environmental temperatures. Moreover, calves that received Cr at levels of 0.05 mg/kg of body weighttended to have higher serum concentrations of glucose and higher ratios of insulin to glucose. In heat-stressedpigs, Cr addition (200 ppb) increased blood neutrophils by about 37%. Several studies have asserted that Cr caninhibit inflammation in lactating cows by promoting the release of Hsp72, assisting production of IL-10 andinhibiting degradation of IκBα in HS conditions. In addition, Cr supplementation was observed to possibly havepositive impacts on both cell-mediated and humeral immunity in heat-stressed buffalo calves. Studies over thelast two decades have shown with certainty that chromium supplementation has an impact on many variablesin chickens. Moreover, Cr is believed to increase insulin action in insulin-sensitive tissues (i.e., adipose and muscles), resulting in increased farm animal productivity through the improvement of feed intake, growth rate, carcass quality, reproductive parameters and immune functions.

Extensive production and use of organophosphate pesticide in agriculture, has risen concerned about its ecotoxicity and risk assessment of insecticides, which are more important. Therefore, the present investigation was aimed to study the induction of oxidative stress and DNA damage by organophosphate insecticide profenofos (PFF) in freshwater snail Lymnea luteola (L. luteola). The median lethal value (96 h LC50) of PFF was estimated as 1.26 mg/L for L. luteola in a semi-static system and on the basis of LC50 value three concentrations viz., 0.126 (1/10 of LC50, Sublethal I), 0.63 (1/2 of LC50, Sublethal II) and 0.84 mg/L (2/3 of LC50, Sublethal III) were determined. Snails were exposed to above-mentioned concentrations of PFF along with solvent control (acetone) and negative control for 96 h. The haemolymph was collected at 24 and 96 h of after treatment. In heamolymph of PFF exposed snail, lipid peroxide, glutathione reduced glutathione S transferase and superoxide dismutase activities at the tested concentrations significantly differ from those in the control. The genotoxicity induced in hemocytes of treated snails was measured by alkaline single cell gel electrophoresis assay. The data of this experiment demonstrated significantly enhancement of oxidative stress and DNA damage in the treated snails as compared to controls. Also, we observed statistically significant correlations of ROS with DNA damage (% tail DNA) (R2 = 0.9708) for 24 h and DNA damage (R2 = 0.9665) for 96 h. Results of the current experiment can be useful in risk evaluation of PFF among aquatic organisms. The study confirmed the use of comet assay for in vivo laboratory experiments using freshwater snail for selecting the toxic potential of industrial chemicals and environmental contaminants.

Indium tin oxide (ITO) nanoparticles (NP) have extensive applications in industrial fields, and concerns regarding their potential toxicity in humans and environmental impact have increased. Since exposure to ITO NP is mainly via skin and inhalation, this study was conducted utilizing human lung epithelial (A549) cell line. Cells were exposed to different concentrations of the ITO NP for 24 and 48 hr. A severe cytotoxic response of ITO NP was observed as evident by the (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and neutral red uptake assays after 48 hr exposure. ITO NP significantly reduced glutathione levels with a concomitant increase in lipid hydroperoxide levels, superoxide activity, and reactive oxygen species (ROS) generation after exposure. A significant induction in caspase activity and formation of condensed chromosomal bodies was also observed after ITO NP (10 or 25 µg/ml) exposure. Furthermore, a significant induction in DNA damage was observed by the Comet assay in cells expo...

Nanoscale silica is an important industrial material and extensively used in medicines. The objective of this study was to determine potential cytotoxicity and genotoxic effects attributed to nanosilica exposure in mouse embryonic fibroblasts (L929) cells. Nanosilica produced mild cytotoxicity in L929 cells. Results showed that nanosilica increased thiobarbituric acid reactive substance levels and enhanced superoxide dismutase activity but decreased levels of glutathione. This was accompanied by a concomitant generation of reactive oxygen species, loss of mitochondrial membrane potential, and activation of caspase-3 activity. In addition, in the single-cell gel test, nanosilica (50–300 μg/ml) at two treatment times 24 and 48 hr produced concentration- and time-dependent increase of DNA damage. Therefore, the obtained results indicate that nanosilica may induce genotoxic effects in cultured L929 cells associated with induction of oxidative stress.

Daoud Ali,1 Abhilasha Tripathi,2 Hussain Al Ali,3 Yadvendra Shahi,2 Kamlesh K Mishra,2 Saud Alarifi,1 Abdullah A Alkahtane,1 Salem Manohardas1 1Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia; 2CytoGene Research and Development, Lucknow, India; 3Centre of Excellence for Genomics, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia Abstract: There are a large number of agricultural workers who are exposed to pesticides through skin and inhalation. The best approach to identify altered molecular pathways during dermal exposure to pesticides is relevant to risk-associated concern about skin safety. In this study, we investigated the cytotoxic effect of zineb, a fungicide, in human keratinocyte (HaCaT) cells. HaCaT cells were treated with zineb (1–40 µg/mL) for 24 hours. Cellular and molecular mechanisms of cell toxicity were investigated through MTT and neutral red-uptake assays. Zineb reduced viability of HaCaT cells and induced apoptosis in a concentration-dependent manner. Zineb increased levels of Bax and caspase 3 and inhibited the level of Bcl2, which subsequently induced apoptosis via the Bax/Bcl2 and caspase pathway. Therefore, zineb could have induced apoptosis through the mitochondrial pathway in HaCaT cells. Our study suggests that zineb is cytotoxic to HaCaT cells via the induction of apoptosis and oxidative stress in vitro. Keywords: zineb, HaCaT cells, apoptosis, MTT assay, DNA damage

The plasma levels of testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) were evaluated in Arabian sand gazelles Gazalla subgutrosa marica to reveal their relation with the sexual desire and testicular efficiency. The levels of those hormones fluctuated over the year; the FSH peak (2.212 ml/mlu) was in October (the beginning of reproductive season). LH level peaked in November (0.73 ml/mlu), while the testosterone level started to increase from July and reached its peak during September and October (340.38 and 419. 5 ng/dl, respectively) and decreased rapidly after November. The levels of some semen inorganic constituents were also measured, the average of sodium, potassium and chloride concentrations were 652.75 ± 124 ± 2.3 and 7.2 ± 0.15 ml mol/L, respectively. Fructose level averaged 141 ± 3.5 mg /dl. The use of the reproductive biotechnologies, which aim to preserve the endangered mammals including Gazelles, is restricted by several factors and depends upon the understanding of the relevant reproductive physiology. In conclusion, sexual hormones were strongly influenced by season. The results from this study suggest more investigation on the reproductive physiological research in order to detect the suitable period for semen collection of Arabian Sand Gazelles ( G. subgutturosa marica ) in Saudi Arabia. Keywords: Testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), fructose and Gazalla subgutrosa marica African Journal of Biotechnology , Vol 13(52) 4647-4652

Extensive applications of cerium oxide (CeO2) nanoparticles require a better understanding of their possible effects on human health. However, data demonstrating the effect of CeO2 nanoparticles on the human skin melanoma cell remain scanty. In the current study, we determined the mechanism through which CeO2 nanoparticles (APS

Recently we have reported potent anti-cancer actions of various steroidal Na + /K + ATPase inhibitors in multiple cell lines. Furthermore, the most powerful compound identified in this study, the 3-[(R)-3-pyrrolidinyl]oxime derivative (3-R-POD), was highly effective in various tumor cell lines in vitro, and exhibited significant tumor growth inhibition in prostate and lung xenografts in vivo. In the present study we have addressed the molecular mechanisms implicated in the anti-cancer actions of 3-R-POD. We report here that 3-R-POD induces strong apoptotic responses in A549 lung- and in DU145 prostate- cancer cells. These effects are accompanied by significant upregulation of caspase-3 activity. Focussing on A549 cells, we further demonstrate late downregulation of BCL-2- and upregulation of c-Fos- gene transcription. In addition, the steroidal Na + /K + ATPase inhibitor induced late de-phosphorylation of Focal Adhesion Kinase (FAK) and activation of p38 MAPK. Our findings suggest that the steroidal Na + /K + ATPase inhibitor 3-R-POD induces apoptosis, paralleled by altered BCL-2 and c-Fos gene transcription, inhibition of the pro-survival FAK signalling, up-regulation of the pro-apoptotic p38 MAPK pathway and stimulation of caspase-3 activity.

Toll-like receptor 3 (TLR3) plays a key role in innate immunity by recognizing pathogenic, double-stranded RNAs. Thus, activation of TLR3 is a major factor in antiviral defense and tumor eradication. Although downregulation of TLR3 gene expression has been mainly reported in patients infected with hepatitis C virus (HCV), the influence of TLR3 genotype on the risk of HCV infection, HCV-related cirrhosis, and/or hepatocellular carcinoma (HCC) remains to be determined. Single-nucleotide polymorphisms (SNPs) within the TLR3 gene and their associations with HCV-related disease risk were investigated in a Saudi Arabian population in this study. Eight TLR3 SNPs were analyzed in 563 patients with HCV, which consisted of 437 patients with chronic HCV infections, 88 with HCV-induced liver cirrhosis, and 38 with HCC. A total of 599 healthy control subjects were recruited to the study. Among the eight TLR3 SNPs studied, the rs78726532 SNP was strongly associated with HCV infection when compared to that in healthy control subjects. The rs5743314 was also strongly associated with HCV-related liver disease progression (cirrhosis and HCC). In summary, these results indicate that distinct genetic variants of TLR3 SNPs are associated with HCV infection and HCV-mediated liver disease progression in the Saudi Arabian population.

Photodynamic inactivation of Leishmania spp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency against Leishmania tropica promastigotes and axenic amastigotes in vitro . The uptake of these PCs by both Leishmania stages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation of Leishmania spp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitized Leishmania tropica strains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ∼650 nm) at a fluence of 1 to 2 J cm −2 . Quantitative fluorescence assays based on the loss of GFP/CFSE from live Leishmania tropica showed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Leishmania tropica strains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC 50 s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation of Leishmania spp. for use as vaccines or vaccine carriers.

Huma Ali,1 Savita Dixit,1 Daoud Ali,2 Abdullah A Alkahtane,2 Saud Alarifi,2 Bahy A Ali,2,3 Saad Alkahtani2 1Department of Chemistry, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh, India; 2Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia; 3Department of Nucleic Acids Research, Genetic Engineering and Biotechnology Research Institute, City Science Research and Technology Application, Alexandria, Egypt Abstract: Quercetol is a polyphenolic molecule present in vegetables and fruits, and is beneficial to human and animal health. The current work aimed to test cytotoxic and apoptotic effects of quercetol on HepG2 cells. Quercetol was isolated from Ocimum sanctum and characterized by gas chromatography–tandom mass spectrometry (GC-MS/MS), nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. Quercetol (50–600 µg/mL) was examined for cytotoxic activity by tetrazolium salt and neutral red uptake tests and comet assay for genotoxicity, using HepG2 cells, over 24 hours. Data from 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and neutral red uptake tests demonstrated quercetol-induced cytotoxicity in HepG2 cells in a concentration-dependent manner. With 4',6-diamidino-2-phenylindole staining, a significant induction of chromosomal condensation was observed at 300 µg/mL of quercetol. DNA fragmentation analysis showed that quercetol produced cell death in HepG2 cells in a concentration-dependent manner. Thus, our study suggests that an environmentally relevant concentration of quercetol, which was a chemically standardized extract from O. sanctum, induced cell death and DNA damage in HepG2 cells. Keywords: NMR, FTIR, quercetol, HepG2 cells, MTT assay, apoptosis, comet assay