Isolation and characterization of novel cadmium-resistant Escherichia fergusonii ZSF-15 from industrial effluent for flocculant production and antioxidant enzyme activity.

Cadmium (Cd) is a highly toxic metal that frequently contaminates our environment. In this study, the bioflocculant-producing, cadmium-resistant Escherichia fergusonii ZSF-15 was characterized from Paharang drain, Bawa Chak, Faisalabad, Pakistan. The Cd-resistant E. fergusonii was used to determine the bioflocculant production using yeast-peptone-glycerol medium (pH 6.5) supplemented with 50 mg L-1 of Cd. The culture was incubated for 3 days at 37 °C in a rotary shaker at 120 rpm. The fermentation broth was centrifuged at 4000 g for 10 min after the incubation period. The maximum flocculating activity by isolate ZSF-15 was found to be 71.4% after 48 h of incubation. According to the Fourier transform infrared spectroscopy analysis, the bioflocculant produced by strain ZSF-15 was comprised of typical polysaccharide and protein, i.e. hydroxyl, carboxyl, and amino groups. The strain ZSF-15 exhibited bioflocculant activity at range of pH (6-8) and temperature (35-50℃). Maximum flocculation activity (i.e. 71%) was observed at 47℃, whereas 63% flocculation production was observed at pH 8. In the present study, antioxidant enzyme profile of ZSF-15 was also evaluated under cadmium stress. A significant increase in antioxidant enzymes including superoxide dismutase (118%) and ascorbate peroxidase (28%) was observed, whereas contents of catalase (86%), glutathione transferase (13%), and peroxidase (8%) were decreased as compared to control.

Ameliorative potential of eriocitrin against cadmium instigated hepatotoxicity in rats via regulating Nrf2/keap1 pathway.

BACKGROUND: Cadmium (Cd) is a hazardous heavy metal that adversely affects the vital body organs particularly liver. Eriocitrin (ERCN) is a plant-based flavonoid that is well-known for its wide range of pharmacological potential. This research trial was aimed to determine the ameliorative potential of ERCN against Cd provoked hepatotoxicity in rats. METHODOLOGY: Twenty-four rats (Rattus norvegicus) were apportioned into control, Cd treated (5 mg/kg), Cd (5 mg/kg) + ERCN (25 mg/kg) and only ERCN (25 mg/kg) administrated group. Expressions of Nrf2/Keap1 pathway and apoptotic markers were assessed through qRT-PCR. The levels of inflammatory and liver function markers were evaluated by using standard ELISA kits. KEY FINDINGS: Cd exposure reduced the expression of Nrf2 and anti-oxidant genes as well as the activity of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione (GSH) contents while escalating the expression of Keap1. Furthermore, Cd intoxication augmented malondialdehyde (MDA) and reactive oxygen species (ROS) levels in hepatic tissues. Exposure to Cd resulted in a notable elevation in the levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Cd administration upregulated nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels as well as cyclooxygenase-2 (COX-2) activity. Furthermore, Cd administration upsurged Bax and Caspase-3 expression while reducing the expression of Bcl-2. Moreover, Cd intoxication disrupted the normal architecture of hepatic tissues. However, supplementation of ERCN significantly (p < 0.05) ameliorated the aforementioned disruptions induced by Cd intoxication. CONCLUSION: ERCN treatment remarkably ameliorated the hepatic tissues owing to its antioxidant, anti-inflammatory, and anti-apoptotic potentials. These findings underscore the therapeutic potential of ERCN to counteract the adverse effects of environmental pollutants on hepatic tissues.

In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma.

NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).Communicated by Ramaswamy H. Sarma.

The role of bixin as antioxidant, anti-inflammatory, anticancer, and skin protecting natural product extracted from Bixa orellana L.

Since long, medicinal plants or herbs are being used in different traditional treatment systems as therapeutic agents to treat a variety of illnesses. Bixa orellana L., an medicinal plant (family: Bixaceae), is an Ayurvedic herb used to treat dyslipidemia, diarrhoea, and hepatitis since ancient times. B. orellana L., seeds contain an orange-red coloured component known as bixin (C25H30O4), which constitutes 80% of the extract.Chemically, bixin is a natural apocarotenoid, biosynthesized through the oxidative degradation of C40 carotenoids. Bixin helps to regulate the Nrf2/MyD88/TLR4 and TGF-1/PPAR-/Smad3 pathways, which further give it antifibrosis, antioxidant, and anti-inflammatory properties. This current review article presents a comprehensive review of bixin as an anti-inflammatory, antioxidant, anticancer,and skin protecting natural product. In addition, the biosynthesis and molecular target of bixin, along with bixin extraction techniques, are also presented.

Comparative analysis of phyto-fabricated chitosan, copper oxide, and chitosan-based CuO nanoparticles: antibacterial potential against Acinetobacter baumannii isolates and anticancer activity against HepG2 cell lines.

The aim of this study was to provide a comparative analysis of chitosan (CH), copper oxide (CuO), and chitosan-based copper oxide (CH-CuO) nanoparticles for their application in the healthcare sector. The nanoparticles were synthesized by a green approach using the extract of Trianthema portulacastrum. The synthesized nanoparticles were characterized using different techniques, such as the synthesis of the particles, which was confirmed by UV-visible spectrometry that showed absorbance at 300 nm, 255 nm, and 275 nm for the CH, CuO, and CH-CuO nanoparticles, respectively. The spherical morphology of the nanoparticles and the presence of active functional groups was validated by SEM, TEM, and FTIR analysis. The crystalline nature of the particles was verified by XRD spectrum, and the average crystallite sizes of 33.54 nm, 20.13 nm, and 24.14 nm were obtained, respectively. The characterized nanoparticles were evaluated for their in vitro antibacterial and antibiofilm potential against Acinetobacter baumannii isolates, where potent activities were exhibited by the nanoparticles. The bioassay for antioxidant activity also confirmed DPPH scavenging activity for all the nanoparticles. This study also evaluated anticancer activities of the CH, CuO, and CH-CuO nanoparticles against HepG2 cell lines, where maximum inhibitions of 54, 75, and 84% were recorded, respectively. The anticancer activity was also confirmed by phase contrast microscopy, where the treated cells exhibited deformed morphologies. This study demonstrates the potential of the CH-CuO nanoparticle as an effective antibacterial agent, having with its antibiofilm activity, and in cancer treatment.

A Comprehensive Review on Pharmacological Activities of Pachypodol: A Bioactive Compound of an Aromatic Medicinal Plant Pogostemon Cablin Benth.

As is well known, plant products have been increasingly utilized in the pharmaceutical industry in recent years. By combining conventional techniques and modern methodology, the future of phytomedicines appears promising. Pogostemon Cablin (patchouli) is an important herb used frequently in the fragrance industries and has various therapeutic benefits. Traditional medicine has long used the essential oil of patchouli (P. cablin) as a flavoring agent recognized by the FDA. This is a gold mine for battling pathogens in China and India. In recent years, this plant has seen a significant surge in use, and approximately 90% of the world's patchouli oil is produced by Indonesia. In traditional therapies, it is used for the treatment of colds, fever, vomiting, headaches, and stomachaches. Patchouli oil is used in curing many diseases and in aromatherapy to treat depression and stress, soothe nerves, regulate appetite, and enhance sexual attraction. More than 140 substances, including alcohols, terpenoids, flavonoids, organic acids, phytosterols, lignins, aldehydes, alkaloids, and glycosides, have been identified in P. cablin. Pachypodol (C18H16O7) is an important bioactive compound found in P. cablin. Pachypodol (C18H16O7) and many other biologically essential chemicals have been separated from the leaves of P. cablin and many other medicinally significant plants using repeated column chromatography on silica gel. Pachypodol's bioactive potential has been shown by a variety of assays and methodologies. It has been found to have a number of biological activities, including anti-inflammatory, antioxidant, anti-mutagenic, antimicrobial, antidepressant, anticancer, antiemetic, antiviral, and cytotoxic ones. The current study, which is based on the currently available scientific literature, intends to close the knowledge gap regarding the pharmacological effects of patchouli essential oil and pachypodol, a key bioactive molecule found in this plant.

Fisetin Attenuates Arsenic-Induced Hepatic Damage by Improving Biochemical, Inflammatory, Apoptotic, and Histological Profile: In Vivo and In Silico Approach.

Arsenic (As) is a toxic metalloid and human carcinogen that may cause hepatotoxicity. Fisetin (3, 3', 4', 7-tetrahydroxyflavone) is a phytoflavonoid, which shows diverse therapeutic activities. This study aimed to examine the remedial potential of fisetin against As-instigated hepatotoxicity in adult male rats. To accomplish this aim, albino rats (N = 48) were evenly classified into 4 groups: control group, As (10 mg/kg) group, fisetin (2.5 mg/kg) + As (10 mg/kg) group, and fisetin (2.5 mg/kg) group. After one month of treatment, biochemical assay, total protein content (TPC), hepatic serum enzymes, inflammatory as well as pro- or anti-apoptotic markers, and histopathological profile of hepatic tissues were estimated. As administration disordered the biochemical profile by decreasing activities of antioxidant enzymes i.e., catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS), and thiobarbituric acid reactive substances (TBARS). TPC was also considerably reduced after exposure to As. Furthermore, As markedly raised the levels of liver serum enzymes such as aspartate transaminase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) as well as the levels of inflammatory markers, i.e., nuclear factor- κB (NF-κB), tumor necrosis- α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclo-oxygenase-2 (COX-2) activity. Besides, it lowered the level of antiapoptotic markers (Bcl-2) and upregulated the levels of proapoptotic markers (Bax, Caspase-3, and Caspase-9). Additionally, As exposure led to histopathological damage in hepatic tissues. However, fisetin administration remarkably alleviated all the depicted hepatic damages. For further verification, the screening of several dock complexes was performed by using the GOLD 5.3.0 version. Based on docking fitness and GOLD score, the ranking order of receptor proteins with fisetin compound is superoxide dismutase, interleukin, aspartate aminotransferase, alkaline phosphatase, TNF-alpha, alanine transaminase, cyclo-oxygenase 2, antiapoptotic, and glutathione reductase. Out of these three receptor proteins superoxide dismutase, interleukin, and aspartate aminotransferase showed the best interaction with the fisetin compound. In vivo and in silico outcomes of the current study demonstrated that fisetin could potentially ameliorate As-instigated hepatotoxicity.

Effect of nucleated cell count and cryopreservation on engraftment post autologous stem cell transplant.

Using 753 collections from 426 adult haematology patients, we conducted a retrospective, analysis into the effects of overnight storage and nucleated cell counts (NCC) on viable, CD34+ (vCD34+) recovery and engraftment kinetics post autologous stem cell, transplant (ASCT) with peripheral blood stem cells (PBSC). There were significant, differences in vCD34 + recovery ( P < 0.01) after cryopreservation associated with, the fresh NCC of ≥ 300 × 10 6 /mL in products stored overnight, but no association, with time to platelet or neutrophil engraftment post-ASCT was observed for these, products. There was no association of vCD34+ numbers or engraftment kinetics with cryopreserved NCC with either below or greater than the local recommended concentration of 400 × 106 /mL of product. However, there was significant difference in engraftment kinetics in relation to the viable CD34+ dose given at ASCT, in relation to the time to early engraftment and the amount of platelet support given during the engraftment period post-ASCT. We conclude the vCD34+ dose at ASCT is of great importance to early engraftment kinetics and that NCC is an important factor during overnight storage, but not for cryopreservation of PBSC. In light of our findings, we recommend that apheresis products collected in a closed system can safely be stored undiluted overnight.

Chemoprotective effect of vitexin against cisplatin-induced biochemical, spermatological, steroidogenic, hormonal, apoptotic and histopathological damages in the testes of Sprague-Dawley rats.

Cisplatin (CP) is one of the most widely used antineoplastic drugs, which possesses the potential to treat a variety of malignancies. However, it displays numerous side effects as well. Male reproductive dysfunction is one of the most adverse side effects of CP. Vitexin is a naturally occurring flavonoid, which exhibits remarkable antioxidant properties. Present study was designed to evaluate the protective effects of vitexin on CP-induced damages on testes. 48 Sprague-Dawley rats were equally distributed into 4 groups: control, cisplatin (CP), cisplatin + vitexin (CP + VIT) and vitexin (VIT). After 14 days of treatment, evaluation of biochemical, spermatogenic, steroidogenical, hormonal, apoptotic and histopathological parameters was carried out. CP damaged the biochemical profile by reducing activity of CAT, SOD, GPx and GSR, while level of MDA and ROS was increased. It also decreased sperm motility, viability, number of hypo-osmotic tail swelled spermatozoa and epididymal sperm count, besides increasing the sperm morphological anomalies. Moreover, levels of LH, FSH and plasma testosterone were reduced. CP reduced the gene expression of testicular anti-apoptotic marker (Bcl-2) and steroidogenic enzymes (3ß-HSD, 17ß-HSD and StAR), but upregulated the gene expressions of apoptotic markers (Bax and Caspase-3). Besides, CP led to histopathological damages in testicular tissues. However, vitexin reversed all aforementioned damages in testes. Therefore, it is concluded that vitexin could play an effective role as a therapeutic agent against CP-prompted testicular toxicity due to its antioxidant, anti-apoptotic and androgenic potential.

Hepatoprotective role of vitexin against cadmium-induced liver damage in male rats: A biochemical, inflammatory, apoptotic and histopathological investigation.

Cadmium (Cd) is one of the potent occupational and environmental toxicants, which induces oxidative stress to the multiple organs of the body, including liver. The present investigation was planned to evaluate the protective role of vitexin against Cd-prompted hepatotoxicity in rats. 24 male rats were divided into 4 groups viz. control, Cd-induced group (5 mg/kg), Cd + vitexin-treated group (2 mg/kg + 30 mg/kg), and vitexin-treated group (30 mg/kg). After 30 days of treatment, it was indicated that Cd escalated the level of liver function enzymes namely alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) as well as total bilirubin. Whereas the levels of albumin and total proteins were decreased in the rats. Additionally, it reduced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR) and glutathione-S-transferase (GST), in addition to glutathione (GSH) content, whereas levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were escalated. Furthermore, level of nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) as well as the activity of cyclooxygenase-2 (COX-2) were increased. Besides, the level of Bax, caspase-9 and caspase-3 were elevated, while the Bcl-2 level was reduced following the Cd intoxication. Histopathological observation revealed significant hepatic tissue damage in Cd-administered rats. However, treatment of rats with vitexin significantly (p < 0.05) improved the Cd-induced disruptions in biochemical parameters as well as histological damages. Therefore, it is concluded that vitexin could be used as a therapeutic agent to counter the Cd-generated hepatic toxicity in rats owing to its anti-oxidant, anti-apoptotic and anti-inflammatory potential.

Tangeretin ameliorates bisphenol induced hepatocyte injury by inhibiting inflammation and oxidative stress.

Bisphenol A (BPA) is an industrial toxicant that can potentially damage the liver. Tangeretin (TGN) is a natural flavonoid that displays various pharmacological activities. This experiment was carried out to evaluate the protective effects of TGN against BPA-induced hepatic impairment in the male albino rat. Twenty-four male albino rats were equally divided into four different groups: control, BPA (100 mg/kg), BPA + TGN (100 mg/kg + 50 mg/kg) and TGN (50 mg/kg). BPA exposure significantly decreased the activities of catalase (CAT), superoxidase dismutase (SOD), peroxidase (POD), glutathione reductase (GSR), glutathione S-transferase (GST), and glutathione (GSH) content while substantially increasing the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels. A substantial increase in the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) was also observed in BPA treated rats. Moreover, BPA significantly increased the inflammatory markers, including tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß)levels, cyclooxygenase-2 (COX-2) activity, and histopathological damages. However, co-treatment with TGN efficiently minimized the BPA-induced biochemical, inflammatory, and histopathological impairments in rat liver. The present study shows that TNG has significant potential to avert BPA-induced liver damage to its antioxidant and anti-inflammatory properties.

Obesity in women living with HIV aged 45-60 in England: An analysis of the PRIME study.

OBJECTIVES: Menopause contributes to weight gain in women. We explored factors associated with obesity in women with HIV aged 45-60 years. METHODS: The present study is an analysis of cross-sectional questionnaire and clinic data from the Positive Transitions Through the Menopause (PRIME) Study. We categorized body mass index (BMI) as normal/underweight (< 25 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (> 30 kg/m2 ). We used logistic regression to explore demographic, social, lifestyle and clinical factors associated with BMI. RESULTS: We included 396 women in this analysis. Median age was 49 years [interquartile range (IQR): 47-52]. Most (83.6%) were not UK-born; the majority (69.4%) were black African (BA). Median (IQR) BMI was 28.6 (24.6-32.6) kg/m2 ; and 110 (27.8%), 127 (32.1%) and 159 (40.1%) of the women were normal/underweight, overweight and obese, respectively. Median (IQR) BMI did not differ in pre-, peri- and post-menopausal women (p = 0.90). In univariable analysis, being non-UK-born was associated with BMI > 30 kg/m2 [odds ratio (OR) = 1.94, 95% confidence interval (CI): 1.07-3.53]. Compared with BA women, women of other black ethnicities were more likely to be obese (OR = 2.37, 95% CI: 1.02-5.50) whereas white British women were less likely to be obese (OR = 0.34, 95% CI: 0.17-0.68). Current smoking and increasing number of comorbid conditions were associated with increased BMI. We found no association between obesity and socioeconomic status. On multivariable analysis, only ethnicity remained associated with obesity (compared with BA: white British, OR = 0.34, 95% CI: 0.17-0.68; other black, OR = 2.50, 95% CI: 1.07-5.82). CONCLUSIONS: Nearly two-fifths of women had BMI > 30 kg/m2 . Obesity was associated with black ethnicities but not with menopausal status. The combination of obesity and HIV may place women at increased risk of co-morbidities, requiring tailored and culturally appropriate interventions.

Biofabrication of ZnO nanoparticles using Acacia arabica leaf extract and their antibiofilm and antioxidant potential against foodborne pathogens.

Emergence of multidrug resistant pathogens is increasing globally at an alarming rate with a need to discover novel and effective methods to cope infections due to these pathogens. Green nanoparticles have gained attention to be used as efficient therapeutic agents because of their safety and reliability. In the present study, we prepared zinc oxide nanoparticles (ZnO NPs) from aqueous leaf extract of Acacia arabica. The nanoparticles produced were characterized through UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. In vitro antibacterial susceptibility testing against foodborne pathogens was done by agar well diffusion, growth kinetics and broth microdilution assays. Effect of ZnO NPs on biofilm formation (both qualitatively and quantitatively) and exopolysaccharide (EPS) production was also determined. Antioxidant potential of green synthesized nanoparticles was detected by DPPH radical scavenging assay. The cytotoxicity studies of nanoparticles were also performed against HeLa cell lines. The results revealed that diameter of zones of inhibition against foodborne pathogens was found to be 16-30 nm, whereas the values of MIC and MBC ranged between 31.25-62.5 µg/ml. Growth kinetics revealed nanoparticles bactericidal potential after 3 hours incubation at 2 × MIC for E. coli while for S. aureus and S. enterica reached after 2 hours of incubation at 2 × MIC, 4 × MIC, and 8 × MIC. 32.5-71.0% inhibition was observed for biofilm formation. Almost 50.6-65.1% (wet weight) and 44.6-57.8% (dry weight) of EPS production was decreased after treatment with sub-inhibitory concentrations of nanoparticles. Radical scavenging potential of nanoparticles increased in a dose dependent manner and value ranged from 19.25 to 73.15%. Whereas cytotoxicity studies revealed non-toxic nature of nanoparticles at the concentrations tested. The present study suggests that green synthesized ZnO NPs can substitute chemical drugs against antibiotic resistant foodborne pathogens.

Protective effects of vitexin on cadmium-induced renal toxicity in rats.

Cadmium (Cd) is an industrial contaminant that poses severe threats to human and animal health. Vitexin (VIT) is a polyphenolic flavonoid of characteristic pharmacological properties. We explored the curative role of vitexin on Cd-induced mitochondrial-dysfunction in rat renal tissues. Twenty-four rats were equally divided into four groups and designated as control, Cd, Cd + vitexin and vitexin treated groups. The results showed that Cd exposure increased urea and creatinine levels while decreased creatinine clearance. Cd reduced the activities of antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione content in the Cd exposed group. Cd exposure significantly (p < 0.05) elevated the reactive oxygen species (ROS) and Thiobarbituric acid reactive substances (TBARS) levels in rat kidney. Cd also caused a significant (p < 0.05) reduction in the mitochondrial TCA-cycle enzymes, including isocitrate dehydrogenase, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, and malate-dehydrogenase activities. Besides, mitochondrial respiratory chain enzymes, including NADH-dehydrogenase, coenzyme Q-cytochrome reductase, succinic-coenzyme Q, and cytochrome c-oxidase activities were also decreased under Cd exposure. Cd exposure also damaged the mitochondrial membrane potential (MMP). However, VIT treatment potentially reduced the detrimental effects of Cd in the kidney of rats. In conclusion, our study indicated that the VIT could attenuate the Cd-induced renal toxicity in rats.

Administration of Vaccine Preservative Thimerosal Produces Impairment in Rat Liver

Abstract The present research was planned to analyze the toxic effects of thimerosal on rat liver. Mercury and mercury compounds are universally known toxicants for animals and humans. Thimerosal is widely used in the vaccines as a preservative which contains 49.6% mercury. Twenty-four adult male albino rats were distributed into four groups (n=6). The first group was considered as a control group. While, second, third and fourth groups were intoxicated with 0.5, 10 and 50 µg/kg thimerosal (i.m.) respectively. After 30 days, rats were slaughtered to analyze the liver tissues. The results of the experiment exposed that thimerosal instigated significant (p<0.05) increase in alanine transaminase (ALT), alkaline phosphatase (ALP) and aminotransferase (AST) levels. Catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) activities and Glutathione (GSH) and protein levels were significantly (p<0.05) reduced. Furthermore, significant increases in Hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) level and DNA damage was observed. Histopathological study revealed severe damages, e.g. fatty alterations, deterioration of lobular structure and degeneration of nuclei in hepatic tissues of thimerosal treated rats. Results of present investigation revealed that thimerosal induces hepatotoxicity at different levels.

Biotechnological approaches to the production of plant-derived promising anticancer agents: An update and overview.

The plant kingdom is a rich source of bioactive compounds, many of which have been used since pre-history for their therapeutic properties to treat a range of illnesses. These metabolites have recently attracted attention to their antineoplastic activities to treat various cancers relying on different mechanisms. Some of these molecules are glycosides, which have proven useful as anti-cancer agents, namely podophyllotoxin (PPT) anaryltetralin lignan or alkaloids. There are three primary forms of alkaloids, such as indole alkaloids (vincristine and vinblastine from Catharanthus roseus), quinoline alkaloid (camptothecin from Camptotheca acuminata), and diterpenoid alkaloid (taxol and it's analogous from Taxus and Corylus species). This review considers various plant biotechnology approaches used to enhance the production of these anticancer molecules in different species. In this regard, many in vitro culture techniques such as stimulation of suspension culture and hairy roots are being used to investigate the effects of plant growth regulators and elicitors on various explants.

In vitro anti-leishmanial activity of Prunus armeniaca fractions on Leishmania tropica and molecular docking studies.

Prunus armeniaca (L.) is a member of the Rosaceae, subfamily Prunoideae, shows anticancer, antitubercular, antimutagenic, antimicrobial, antioxidant, and cardioprotective activities. Here we fractionated the leaves extract of this highly medicinally important plant for antileishmanial activity. In the current study, the leaves extract was fractionated and characterized using column and thin layer chromatography by n-hexane, ethyl acetate, and methanol solvents. Twelve fractions were isolated and subjected for evaluation of their cytotoxicity and in vitro antileishmanial activity against promastigotes and amastigotes of Leishmania tropica. Among all fractions used, the fraction (F7) exhibited the strongest antileishmanial activity. The bioactive fraction was further characterized by spectroscopy (FTIR, UV-Vis), and GC-MS analysis. The in silico docking was carried out to find the active site of PTR1. All derived fractions exhibited toxicity in the safety range IC50 > 100 µg/ml. The fraction (F7) showed significantly the highest antipromastigotes activity with IC5011.48 ± 0.82 µg/ml and antiamastigotes activity with IC50 21.03 ± 0.98 µg/ml compared with control i.e. 11.60 ± 0.70 and 22.03 ± 1.02 µg/ml respectively. The UV-Vis spectroscopic analysis revealed the presence of six absorption peaks and the FTIR spectrum revealed the presence of alkane, aldehyde, carboxylic acid, thiols, alkynes, and carbonyls compounds The GC-MS chromatogram exhibited the presence of nine compounds: (a) benzeneethanol, alpha, beta dimethyl, (b)carbazic acid, 3-(1 propylbutylidene)-, ethyl ester, (c)1, 2-benzenedicarboxylic acid, diisooctyl ester, (d)benzeneethanamine a-methyl, (e)2aminononadecane, (f)2-heptanamine-5-methyl, (g)cyclobutanol, (h)cyclopropyl carbine, and (i)nitric acid, nonyl ester. Among all compounds, the 1, 2-benzenedicarboxylic acid, diisooctyl ester bound well to the PTR1 receptor. Fraction (F7) showed acceptable results with no cytotoxicity. However, in vivo studies are required in the future.

Apparent nutrient digestibility of carbohydrate (corn) in Cirrhinus mrigala under the influence of chromium chloride hexahydrate / Digestibilidade aparente de nutrientes oriundos de carboidratos (milho) em Cirrhinus mrigala sob a influência do cloreto de cromo hexa-hidratado

Abstract A feeding trial was carried out to assess the effect of dietary chromium supplementation on apparent nutrient digestibility coefficient (%) of gelatinized and non-gelatinized corn in Cirrhinus mrigala fingerlings for 90 days. Using various levels of chromium chloride hexahydrate six test diets designated as T1 (G/0.0 Cr2Cl3.6H2O mg Kg-1), T2 (NG/0.0 Cr2Cl3.6H2O mg Kg-1), T3 (G/0.2 Cr2Cl3.6H2O mg Kg-1), T4 (NG/0.2 Cr2Cl3.6H2O mg Kg-1), T5 (G/0.4 Cr2Cl3.6H2O mg Kg-1) and T6 (NG/0.4 Cr2Cl3.6H2O mg Kg-1) were prepared. Results showed highest apparent digestibility coefficient (ADC) of nutrients dry matter, crude lipid and gross energy in test diet T5 that was gelatinized and supplemented with chromium 0.4 mg/Kg while, for crude protein higher value of nutrient digestibility was recorded in T3 test diet (G/0.2 Cr2Cl3.6H2O mg/Kg). It was concluded that chromium supplementation with gelatinized corn in fish (Cirrhinus mrigala) diet can improve the nutrients digestibility more efficiently.

Resumo Um experimento referente à alimentação foi realizado para avaliar o efeito da suplementação dietética de cromo, no coeficiente de digestibilidade aparente do nutriente (%) do milho gelatinizado e não gelatinizado em alevinos de Cirrhinus mrigala por 90 dias. Usando vários níveis de cloreto de cromo hexa-hidratado, seis dietas testes foram designadas e preparadas como: T1 (G/0,0 Cr2Cl3.6H2O mg Kg-1); T2 (NG/0,0 Cr2Cl3.6H2O mg Kg-1); T3 (G/0,2 Cr2Cl3.6H2O mg Kg-1); T4 (NG/0,2 Cr2Cl3.6H2O mg Kg-1); T5 (G/0,4 Cr2Cl3.6H2O mg Kg-1) e T6 (NG/0,4 Cr2Cl3.6H2O mg Kg-1). Os resultados mostraram maior coeficiente de digestibilidade aparente (CDA) em matéria seca de nutrientes, lipídios brutos e energia bruta na dieta teste T5, que foi gelatinizada e suplementada com cromo 0,4 mg / Kg; enquanto que para a proteína bruta, foi registrada maior digestibilidade dos nutrientes na dieta teste T3 (G/0,2 Cr2Cl3.6H2O mg/Kg). Concluiu-se que a suplementação de cromo com milho gelatinizado na dieta de peixes (Cirrhinus mrigala) pôde melhorar a digestibilidade dos nutrientes de forma mais eficiente.

Ibrutinib-related atrial fibrillation: A single center Australian experience.

BACKGROUND: Ibrutinib increases the risk of atrial fibrillation (AF) and is associated with bleeding tendencies. Reported rates of arrhythmia are variable in different studies. The aim of the current analysis was to evaluate the incidence of AF in a single-center cohort of patients. METHODS: This analysis was conducted at Hunter New England Local Health District, Australia between April 1, 2015 and June 30, 2017. We included all consecutive patients commenced on ibrutinib for hematological malignancies. Patients with a history of paroxysmal AF were excluded. The primary end point was incidence of AF. Time to diagnosis and management were secondary outcomes of interest. RESULTS: A total of 24 patients (age 73 ± 9 years, males n = 16 [67%]) were commenced on ibrutinib treatment during the study period with chronic lymphocytic leukemia (n = 21, 88%) as the main indication. During a median follow-up of 12 months, four (17%) patients were diagnosed with AF with increasing age, duration of ibrutinib treatment as associations. The median time to AF diagnosis was 9 (interquartile range [IQR]: 7-18) months. All patients were managed with a rate control strategy with beta blockers as the preferred agents. Three (75%) patients were commenced on anticoagulation for stroke prevention. During a follow-up of 18 (IQR: 17-23) months following AF onset, one patient required hospitalization for AF. There were no bleeding complications reported. CONCLUSIONS: In conclusion, this series noted a higher incidence of AF than previously reported. Oncologists and cardiologists need to be aware of the increased risk of AF in patients receiving ibrutinib.

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy.

Altered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies.