Bernsteingotfredsen8590

Cemtirestat, 3-mercapto-5H-[1,2,4]-triazino[5,6-b] indole-5-acetic acid was recently designed and patented as a highly selective and efficient aldose reductase inhibitor endowed with antioxidant activity. The aim of the present study was to assess the general toxicity of cemtirestat using in silico predictions, in vitro and in vivo assays. ProTox-II toxicity prediction software gave 17 "Inactive" outputs, a mild hepatotoxicity score (0.52 probability) along with a predicted LD50 of 1000 mg/kg. Five different cell lines were used including the immortalized mouse microglia BV-2, the primary human fibroblasts VH10, the insulinoma pancreatic β-cells INS-1E, the human colon cancer cells HCT116 and the human immortalized epithelial endometrial cell lines HIEEC. In contrast to the clinically used epalrestat, cemtirestat showed remarkably low cytotoxicity in several different cell culture viability tests such as MTT proliferation assay, neutral red uptake, BrdU incorporation, WST-1 proliferation assay and propidium iodide staining followed by flow cytometry. In a yeast spotting assay, the presence of cemtirestat in incubation of Saccaromyces cerevisiae at concentrations as high as 1000 μM did not affect cell growth rate significantly. In the 120-day repeated oral toxicity study in male Wistar rats with daily cemtirestat dose of 6.4 mg/kg, no significant behavioral alterations or toxicological manifestations were observed in clinical and pathological examinations or in hematological parameters. In summary, these results suggest that cemtirestat is a safe drug that can proceed beyond preclinical studies. Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.The aim of the present study was to investigate the effects of Cichorium intybus on lipid peroxidation activities of both enzymatic and non-enzymatic antioxidants, inflammatory mediators, myocardial enzymes and histopathology of cardiac tissues in experimental diabetic cardiomyopathy (DCM). DCM was induced by single intraperitoneal injection of streptozotocin (STZ) (40 mg/kg) combined with high energy intake in rats. Seed extract of Cichorium intybus (CIE) (250 mg/kg & 500 mg/kg) was administered orally once a day for 3 weeks. Phytochemical investigations of seed extract revealed presence of some active ingredients such as alkaloids, tannins, saponin, phenols, glycosides, steroids, terpenoids and flavonoids. Seed extract of Cichorium intybus confirmed a significant potency towards restoring the blood glucose, an elevation of the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), blood glutathione (GSH), TNF-α and IL-6 and a reduction in the levels of catalase (CAT) was observed following the STZ treatment. Oxidative stress was accompanied by myocardial degeneration as evidenced by histopathological examination of cardiac tissues. Administration of CIE reduced the lipid peroxides level in heart. Serum levels of AST, GSH, LDH and SOD were brought down to physiological levels by CIE in STZ induced DCM rats. CIE also markedly down-regulated serum TNF-α and IL-6 levels. Catalase that was reduced in serum was brought back to near normal level. The extensive necrotic changes of cardiac tissue by STZ was minimized to normal morphology upon CIE administration. The study demonstrates the cardioprotective effect of CIE via inhibition of oxidative stress and pro-inflammatory cytokines. Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.Himalayan yew (Taxus wallichiana) is in high demand due to the presence of taxol in its bark, needles, and seeds. This metabolite is used for the treatment of breast and ovarian cancer. In addition, Himalayan yew wood is used to prepare slabs (Tabai), coffins (Taabut), for graveyards. Due to illegal cutting of plant parts and other anthropogenic pressures, Himalayan yew is endangered, and threatened with extinction, in Himalaya. This species grows slowly and regenerates poorly, primarily due to low production and delayed germination (1.5-2 years) of its seeds. The study being reported here was conducted to assess the factors (natural and anthropogenic) threatening this species. Nine valleys (Miandam, Kalam, Shinko, Beha, Lalku, Shahgram, Bishigram, Gurnai, and Daral) in the Swat district of Khyber Pakhtunkhwa (KP), Pakistan, have stands of Himalayan yew that were selected for the study. Before the survey was conducted, five informal discussions were carried out to identify people to be interviewed. A survey wy, juvenile plants. In addition to in-situ and ex-situ conservation and management, there is a need for local community involvement in the large-scale reforestation efforts. © 2020 The Authors.The present study explored the phytochemicals, antibacterial, antioxidant and cytotoxic effect of Tridax procumbens leaves. The leaves were dried and extracted with various organic solvents. The leaves contained the phytochemicals such as alkaloids, carbohydrates, polyphenols and tannins respectively. Antimicrobial potentials of the extracts were determined by performing the disc diffusion techniques. Results revealed that different organic solvents extracts namely methanol, ethanol and ethyl acetate extracts documented comparatively good activity against the studied microbial strains. The methanol extract of leaves of T. Cobimetinib procumbens showed combatively better antioxidant potential. The tested plant leaf extract showed high activity against human lung cancer cells than breast cancer cell lines. 250 µg/ml plants extract showed 84 ± 2.8% toxicity against human lung cancer cells. © 2019 Published by Elsevier B.V. on behalf of King Saud University.Fungal keratitis caused by the species of Aspergillus is a common and leading problem in developing countries like India. In this study, a total of 135 isolates from Aspergillus keratitis were studied by sequence analyses of the internal transcribed spacer (ITS) region performed by nucleotide-nucleotide BLAST analysis followed by the initial identification of the isolates based on conidial and colony morphology. The sequence analysis revealed several unusual species which were never reported in eye infections such as A. tamrii, A. tubingensis, A. braslliensis, A. nomius, A. pseudonomius, A. sydowii, Eurotium amstelodami. The sequence analysis of the ITS region; the β-tubulin and calmodulin genes brought out the genetic diversity among the isolates as the study intended to locate a more sensitive target sequence to study genetic diversity among a set of test fungal isolates. The PCR amplified sequences of the test isolates of the study as well as sequences belonging to section Flavi obtained from Genbank database were compared and analyzed along with three standard isolates by phylogenetic tree (Neighbor-joining) as to find out a target region/gene that could produce a better resolution to differentiate the isolates. Accordingly, the calmodulin gene had provided better resolution compared to ITS and β-tubulin to study the diversity among the test Aspergillus species isolated from fungal corneal ulcer. © 2019 The Author(s).The incidence of Alzheimer's disease (AD) has risen exponentially worldwide over the past decade. A growing body of research indicates that AD is linked to diabetes mellitus (DM) and suggests that impaired insulin signaling acts as a crucial risk factor in determining the progression of this devastating disease. Many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias. Despite nationwide efforts to increase awareness, the prevalence of Diabetes Mellitus (DM) has risen significantly in the Middle East and North African (MENA) region which might be due to rapid urbanization, lifestyle changes, lack of physical activity and rise in obesity. Growing body of evidence indicates that DM and AD are linked because both conditions involve impaired glucose homeostasis and altered brain function. Current theories and hypothesis clearly implicate that defective insulin signaling in the brain contributes to synaptic dysfunction and cognitive deficits in AD. In the periphery, low-grade chronic inflammation leads to insulin resistance followed by tissue deterioration. Thus insulin resistance acts as a bridge between DM and AD. There is pressing need to understand on how DM increases the risk of AD as well as the underlying mechanisms, due to the projected increase in age related disorders. Here we aim to review the incidence of AD and DM in the Middle East and the possible link between insulin signaling and ApoE carrier status on Aβ aggregation, tau hyperphosphorylation, inflammation, oxidative stress and mitochondrial dysfunction in AD. We also critically reviewed mutation studies in Arab population which might influence DM induced AD. In addition, recent clinical trials and animal studies conducted to evaluate the efficiency of anti-diabetic drugs have been reviewed. © 2019 Published by Elsevier B.V. on behalf of King Saud University.Endophytic bacterial diversity shows an intricate network of interactions with host plants as they reside in various tissues and organs at certain stages or all stages of their life cycle stimulating the plant growth and fitness. Sunflower is a trendy oilfield crop and variation in its varieties is associated with the dynamics of endophytic diversity. The present study is undertaken to identify and compare the ecological niche of endophytic bacterial communities amongst different tissues of two hybrids varieties Hysun-33 and Hysun-39 of sunflower (Helianthus annuus) at three developmental stages which are vegetative stage I (after 15 days of seeds germination), vegetative stage II (after 30 days of germination) and reproductive stage (after 90 days of germination). A total of 74 endophytes from Hysun-33 and 115 endophytes from Hysun-39 have been isolated from different tissues and growth stages. Amongst plant parts, root tissues harbored higher bacterial inhabitants (44) followed by stem (33), leaf (30) and fria and their beneficial relationship with internal tissues of host plant which may recommend their implementation to crops for better development of agricultural systems. © 2019 Published by Elsevier B.V. on behalf of King Saud University.The study is to scrutinize andrographolides with Indoleamine 2,3-dioxygenase (IDO) inhibitory potential, its molecular mechanism against streptozotocin (STZ) diabetic retinopathy (DR) in Wistar rats. Oxidative stress markers such as Kynurenine metabolites, retinal histopathological changes have been studied. Further, IDO gene expression and docking studies have been performed. Andrographolide treated rats have been reducing the level of thiobarbituric acid reactive substances and protein carbonyls Kynurenine metabolites with an improvement in the level of GSH and expression of IDO as revealed by morphological changes in inner and outer nuclear layer of the retina. The current results of this study have been generated information about an activity of the andrographolide in the essential pocket of IDO. Our results explain, involving IDO and andrographolide would constitute an attempt to identify natural products with therapeutic value and further studies in this direction would be of immense significance in the administration of diabetes and its related problems.