The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study.

The protein kinase TAOK3, belongs to the MAP kinase family, is one of three closely related members, namely TAOK1, TAOK2, and TAOK3. We performed a pan-cancer investigation of TAOK3 across different cancer types, including uterine carcinosarcoma, adenocarcinoma of the stomach and pancreas, and endometrial carcinoma of the uterus, to better understand TAOK3's role in cancer. In at least 16 types of cancer, our findings indicate that TAOK3 expression levels differ considerably between normal and tumor tissues. In addition, our study is the first to identify the oncogenic role of TAOK3 locus S331 and S471 in renal clear cell carcinoma, Glioblastoma Multiforme, hepatocellular carcinoma, Lung adenocarcinoma, and Pancreatic adenocarcinoma, indicating their involvement in cancer progression. In addition, our data analysis indicates that copy number variation is the most prevalent form of mutation in the TAOK3 gene, and that there is a negative correlation between TAOK3 mRNA and DNA promoter methylation. Moreover, our analysis suggests that TAOK3 may serve as a prognostic marker for several kinds of cancer, including Colon adenocarcinoma, renal clear cell carcinoma, Lower Grade Glioma, Lung adenocarcinoma, Mesothelioma, and hepatocellular carcinoma. In addition, our research on signature cancer genes has uncovered a positive association between TAOK3 and SMAD2, SMAD4, and RNF168 in most of the malignancies we have examined. TAOK3 is also correlated with the frequency of mutations and microsatellite instability in four types of cancer. Numerous immune-related genes are closely associated with TAOK3 levels in numerous malignancies. TAOK3 expression is positively correlated with immune infiltrates, which include activated CD4 T cells, CD8 T cells, and type 2T helper cells. Our pan-cancer analysis of TAOK3 provides vital insight into its potential role across a variety of cancer types.

Hepatoprotective activity of depsidone enriched Cladonia rangiferina extract against alcohol-induced hepatotoxicity targeting cytochrome P450 2E1 induced oxidative damage.

Alcoholic liver disease (ALD) is a broad-spectrum disorder, covering fatty liver, cirrhosis, alcoholic hepatitis and in extreme untreated condition hepatocellular carcinoma (HCC) may also develop. Cladonia rangiferina (CR) is a class of lichen having a broad spectrum of pharmacological activity. It is used like traditional natural sources in ancient times in India, China, Sri Lanka, etc. Folkloric record about CR has reported their use as an antimicrobial, antitumor, antioxidant, anti-inflammatory activities, etc. Hence, the present study was requested to ascertain the effect of the ethanolic extract of Cladonia rangiferina (CRE) on alcohol-induced hepatotoxicity. The animals were evaluated for the estimation of the liver in vivo biochemical antioxidant parameters. The liver tissues were further evaluated histopathologically and western blotting examination for localization of apoptotic gene expression that plays a pivotal role in hepatotoxicity. The results of this study reveal that CRE proves to be helpful in the treatment of alcohol-induced hepatotoxicity and oxidative stress. Results of different markers have shown that among all, CRE has demonstrated the best hepatoprotective activity. These observations say about the importance of the components of the extract. The ameliorative action of CRE in alcoholic liver damage may exist due to antioxidant, anti-inflammatory, and anti-apoptotic activities.

Oxidative free radicals scavenging activity (in vitro and in vivo assay) of standardized fractions from the seeds of Argyreia speciosa (Ghav-patta) a traditional Indian medicine.

TRADITIONAL PERTINENCE: Argyreia speciosa Sweet (Linn.), belongs to the family convolvulaceae, a traditional Indian medicinal herb, has been used to treat acute/chronic ulcers, gonorrhea, rheumatoid arthritis and several nervous disorders having a long history. AIM OF THE STUDY: A broad spectrum approach of this work was to find out the antioxidant activity of Argyreia speciosa seeds, in vitro and in vivo antioxidant assay were performed. MATERIAL AND METHODS: Total phenolic content (TPC), reducing power (RP), antioxidant activity (AOA), O 2 · - (superoxide anion), DPPH (1,1-diphenyl-2-picrylhydrazyl) and ˙OH (hydroxyl) radicals scavenging activities, GSH (glutathione), CAT (catalase), SOD (superoxide dismutase) and LPO (lipid peroxidase) are the major parameters which were studied for determining in vitro and in vivo antioxidant property of seed extract & their six fractions obtained from A. speciosa. Carbon tetrachloride (CCl4) induced rat model was used to determine in vivo antioxidant assay of extract and its fractions. RESULTS: Butanol fraction (AS-BF) showed strong antioxidant property and protected oxidative DNA damage. AS-BF was found best as compared to all other fraction for determining antioxidant property of seeds with the reduction in lipid peroxide formation and increment in GSH, CAT and SOD. AS-BF showed the presence of phenolic compounds viz. gallic acid, chlorogenic acid, and ellagic acid. CONCLUSION: From these results, it was proved that A. speciosa seeds prevent tissue damage due to oxidative stress with strong antioxidant activity.

In vitro wound healing activity of 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC) and other isolates of Aegle marmelos L.: Enhances keratinocytes motility via Wnt/ß-catenin and RAS-ERK pathways.

Wound healing is a complex process in which injured skin and tissues repaired by interaction of a complex cascade of cellular events that generates resurfacing, reconstitution and restoration of the tensile strength of injured skin. It follows ß-catenin, extracellular signal regulated kinase (ERK) and Akt signaling pathways. Aegle marmelos L., generally known as bael is found to act as anti-inflammatory, antioxidant and anti-ulcer agent. Furthermore, studies have demonstrated that this Indian traditional medicinal plant, A. marmelos flower extract (AMF) was used for wound injury. Henceforth, the current study was investigated to ascertain the effect of its active constituents in vitro wound healing with mechanism involve in migration of cells and activation of ß-catenin in keratinocytes, inhibition of PGE2 in macrophages and production of collagen in fibroblasts. We have taken full thickness wound of rats and applied AMF for 2 weeks. Cutaneous wound healing activity was performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW264.7 macrophages to determine cell viability, nitric oxide production, collagen expression, cell migration and ß-catenin activation. Results shows that AMF treated rats demonstrated reduced wound size and epithelisation was improved, involved in keratinocytes migration by regulation of Akt signaling, beta-catenin and extracellular signal-regulated kinase (ERK) pathways. AMF and its active constituent's increased mRNA expression, inhibited nitric oxide, PGE2 release, mRNA expression of mediators in RAW 264.7 macrophages and enhances the motility of HaCaT keratinocytes in vitro wound healing of rats.

Top 10 most used drugs in the Kingdom of Saudi Arabia 2010-2015.

Medications usage has become a significant part of contemporary life. Many studies indicate that there is an excessive use and a considerable waste of medicines. This descriptive study aims at identifying the most used medicines in Saudi Arabia from 2010 to 2015 according to the statistics of specialized companies in the field. Comparison of the most commonly used drugs with those in the United States aims at clarifying similarities and differences. The results showed that the use of antibiotics and analgesics still accounted for the bulk, followed by proton pump inhibitors and anti-diabetics respectively, then anti-hyperlipidemic agents and erectile dysfunction treatments. The causes of this overuse vary according to the studies concerned between the self-medications and the over-prescription of the medication and the failure of the diagnostic and treatment procedures (malpractice). The recommendations are the strict application of prescribed and non-prescribed dispensing systems and the further establishment and application of national guides in the diagnosis and treatment of communicable diseases. The repetition of such studies is useful in reviewing health policies and regulations related to health practice in general and pharmacological policies in particular.

Prognostic Values of Gene Copy Number Alterations in Prostate Cancer.

Whilst risk prediction for individual prostate cancer (PCa) cases is of a high priority, the current risk stratification indices for PCa management have severe limitations. This study aimed to identify gene copy number alterations (CNAs) with prognostic values and to determine if any combination of gene CNAs could have risk stratification potentials. Clinical and genomic data of 500 PCa cases from the Cancer Genome Atlas stable were retrieved from the Genomic Data Commons and cBioPortal databases. The CNA statuses of a total of 52 genetic markers, including 21 novel markers and 31 previously identified potential prognostic markers, were tested for prognostic significance. The CNA statuses of a total of 51/52 genetic markers were significantly associated with advanced disease at an odds ratio threshold of ≥1.5 or ≤0.667. Moreover, a Kaplan-Meier test identified 27/52 marker CNAs which correlated with disease progression. A Cox Regression analysis showed that the amplification of MIR602 and deletions of MIR602, ZNF267, MROH1, PARP8, and HCN1 correlated with a progression-free survival independent of the disease stage and Gleason prognostic group grade. Furthermore, a binary logistic regression analysis identified twenty-two panels of markers with risk stratification potentials. The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa.

A Descriptive Review of the Prevalence and Usage of Traditional and Complementary Medicine among Saudi Diabetic Patients.

Diabetes mellitus represents a major burden in Saudi Arabia where seven million (20% of population) are living with diabetes. This article reviews the literature on usage of traditional and complementary medicine (T&CM) therapies among Saudi diabetic patients, focusing in particular on identifying the prevalence as well as discussing their safety and efficacy. Three databases (PubMed, Cochrane, and ScienceDirect) were searched prior to December 10, 2017, for articles published in peer-reviewed journals that reported primary data on the use of traditional and complementary medicine therapies among diabetic patients in Saudi Arabia. Six studies were selected according to the inclusion/exclusion criteria. In conclusion, the prevalence of use of T&CM therapies among diabetics in Saudi Arabia was 32.18%. This review identified that the most used T&CM therapy among diabetics was herbal treatment. The most used herbs were fenugreek, black seeds, neem, myrrh, helteet, harmel, and aloes. There is insufficient or little evidence to support the efficacy of the most identified herbs and therapies. This review is raising the safety concerns about the used herbs and complementary therapies which were commonly used without any medical consultation.

Possible involvement of the lipoxygenase and leukotriene signaling pathways in cisplatin-mediated renal toxicity.

PURPOSE: The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively. The serum and kidney levels of LTB4 and inflammatory markers were also estimated. RESULTS: CPT renal toxicity was established as the creatinine and urea clearance levels were significantly reduced, while the serum levels of creatinine and urea were markedly increased. We reported a considerable up-regulation in the mRNA and protein expression levels of 5-LOX, FLAP, 12-LOX, LTA4 hydrolase, LTC4 synthase, LTB4 receptor, and Cys LT receptor types 1 and 2, while 15-LOX expression did not significantly change in the CPT group. Additionally, LTB4 and inflammatory indicators in serum and renal levels were elevated significantly in the CPT group. Histopathological examination clearly showed the nephrotoxic changes in the renal tissues of CPT-challenged animals. CONCLUSIONS: Our findings suggested, for the first time, the participation of LOX enzymes and products in the signaling pathway leading to CPT-associated nephrotoxicity, which could be the foundation stone for combining LOX pathway attenuators with CPT therapy to decrease CPT-associated renal toxicity.

Anti-osteoporotic effects of an antidepressant tianeptine on ovariectomized rats.

In the current investigation, the potential alleviating effects of tianeptine against bone loss induced in ovariectomized (OVX) rats was determined. Two weeks following a bilateral ovariectomy operation, tianeptine treatment (12.5 and 25mg/kg/twice/d) was initiated and continued for twenty-eight consecutive days. Changes in serum and urinary bone turnover biomarkers and osteoclastogenesis-inducing factors were estimated. The femoral bone mineral content was estimated using inductively-coupled-plasma mass spectrometry. Morphometric alterations of distal femoral bones were observed in the cortical and trabecular structures using micro-CT. Finally, femur bones were assessed for histopathological changes. The lack of estrogen significantly increased the levels of bone turnover biomarkers and inflammatory mediators. Mineral concentrations in the femoral bones were reduced in the OVX group. Furthermore, the femoral bone micro-architecture determined using micro-CT and histopathology were significantly altered by estrogen deficiency. Tianeptine, particularly the higher dose, corrected the elevated levels of bone metabolic products and pro-inflammatory cytokines. Tianeptine also improved mineral concentrations in femoral bones and the disturbed morphometric and histopathological features in OVX rats. In conclusion, tianeptine alleviated the osteoporotic changes in OVX animals, which may be via inhibition of the hypothalamic-pituitary-adrenal axis stress and osteoclastogenesis-provoking factors, suggesting attenuation of bone matrix degradation and osteoclast stimulation.