Protective Effect of Hirsutidin against Rotenone-Induced Parkinsonism via Inhibition of Caspase-3/Interleukins-6 and 1ß.

A participant of the chemical family recognized as anthocyanins, hirsutidin is an O-methylated anthocyanidin. It is a natural substance, i.e., existing in Catharanthus roseus (Madagascar periwinkle), the predominant component in petals, as well as callus cultures. The literature review indicated a lack of scientifically verified findings on hirsutidin's biological activities, particularly its anti-Parkinson's capabilities. Using the information from the previous section as a reference, a present study has been assessed to evaluate the anti-Parkinson properties of hirsutidin against rotenone-activated Parkinson's in experimental animals. For 28 days, rats received hirsutidin at a dose of 10 mg/kg and rotenone at a dose of 0.5 mg/kg s.c. to test the neuroprotective effects. The hirsutidin was given 1 h before the rotenone. Behavioral tests, including the rotarod test, catalepsy, Kondziela's inverted screen activity, and open-field analysis, were performed. The levels of neurotransmitters (5-HT, DOPAC, 5-HIAA, dopamine, and HVA), neuroinflammatory markers (TNF-α, IL-6, IL-1ß, caspase-3), an endogenous antioxidant, nitrite content, and acetylcholine were measured in all the rats on the 29th day. Hirsutidin exhibited substantial behavioral improvement in the rotarod test, catalepsy, Kondziela's inverted screen activity, and open-field test. Furthermore, hirsutidin restored neuroinflammatory markers, cholinergic function, nitrite content, neurotransmitters, and endogenous antioxidant levels. According to the study, hirsutidin has anti-inflammatory and antioxidant characteristics. As a result, it implies that hirsutidin may have anti-Parkinsonian effects in rats.

Evaluation of Antidiabetic Effect of Luteolin in STZ Induced Diabetic Rats: Molecular Docking, Molecular Dynamics, In Vitro and In Vivo Studies.

Despite the existence of modern antidiabetic medications, diabetes still affects millions of individuals worldwide, with a high death and disability rate. There has been a concerted search for alternative natural medicinal agents; luteolin (LUT), a polyphenolic molecule, might be a good choice, both because of its efficacy and because of it having fewer side effects, compared to conventional medicines. This study aims to explore the antidiabetic potential of LUT in diabetic rats, induced by streptozotocin (STZ; 50 mg/kg b.w.), intraperitoneally. The level of blood glucose, oral glucose tolerance test (OGTT), body weight, glycated hemoglobin A1c (HbA1c), lipidemic status, antioxidant enzymes, and cytokines were assessed. Also, its action mechanism was explored through molecular docking and molecular dynamics simulations. Oral supplementation of LUT for 21 days resulted in a significant decrease in the blood glucose, oxidative stress, and proinflammatory cytokine levels, and modulated the hyperlipidemia profile. LUT also ameliorated the tested biomarkers of liver and kidney function. In addition, LUT markedly reversed the damage to the pancreas, liver, and kidney cells. Moreover, molecular docking and molecular dynamics simulations revealed excellent antidiabetic behavior of LUT. In conclusion, the current investigation revealed that LUT possesses antidiabetic activity, through the reversing of hyperlipidemia, oxidative stress, and proinflammatory status in diabetic groups. Therefore, LUT might be a good remedy for the management or treatment of diabetes.

Bone mass in Saudi women aged 20-40 years: the association with obesity and vitamin D deficiency.

This study describes that low bone density is prevalent in premenopausal Saudi women, especially women of normal weight and vitamin D deficiency. Although BMD is higher in obese young women, this may not be beneficial later in life in conjunction with persistent vitamin D deficiency. INTRODUCTION: Not attaining peak bone mass is one crucial factor contributing to the risk of developing osteoporosis and suffering fractures in later life. The objectives of this study were to describe the normal range of bone mineral density (BMD) and bone mineral content (BMC) in premenopausal Saudi women in relation to obesity and vitamin D insufficiency. METHODS: A cross-sectional study involving 312 healthy Saudi women aged 20-40. All women were clinically examined. BMD (g/cm2) and BMC (g) assessed at total body (TB), femoral neck (FN) and lumbar spine (LS) were performed using dual-energy X-ray absorptiometry (DXA). Obesity was defined as BMI ≥ 30 kg/m2 and vitamin D deficiency defined as 25(OH)D < 50 nmol/L. RESULTS: Almost half of the studied women were obese, and the majority (86.2%) were deficient in vitamin D. Mean BMD in TB 1.060 ± 0.091, FN 0.918 ± 0.153 and LS 1.118 ± 0.123 g/cm2, while TB-BMC 2077 ± 272 g. When classified by BMI, the proportion with low bone density was 2-3 times higher among the normal weight compared to the obese women, p < 0.001. In the cohort overall, ~ 19% of these young premenopausal women had osteopenia or osteoporosis at the femoral neck, but 26% in normal weight, vitamin D deficient women. CONCLUSION: This study shows low bone density in premenopausal Saudi women, particularly those with normal weight. While obesity appears to confer some protection against vitamin D deficiency at this age, this is assumed to change in later life.

ICT Application and Use in Health Sciences Research at the Global Level: A Scientometric Study.

The growing use of information and communication technology has now expanded to health professionals in practice. This study aimed to highlight the current status of Information and Communication Technology (ICT) use in health sciences as reported in journal papers between 2002 and 2021. This paper presents the annual trends, top institutes and countries, citations, h-index, keywords distribution, and top authors in this research domain. The data were extracted from the Web of Science database, and R studio and Bibexcel tools were used for analysis. The study analyzed a total of 140 documents published over a span of two decades. Health Care Sciences Services (34) and Computer Science published the most health science articles (29). The USA (19) was the most productive country, followed by England (16) and the Netherlands (15). Berg M was the most productive author, with 36 articles. The results show that institutions such as Erasmus University and Duke University have published numerous articles on the topic, encouraged by specific R&D funding schemes, and made a significant contribution to the development of health sciences research. The findings of this study offer valuable information about international initiatives and projects relevant to the advancement of ICT in health science research, which may be utilized to pinpoint potential future study topics such as artificial intelligence development.

Design, Synthesis, and Bioevaluation of Indole Core Containing 2-Arylidine Derivatives of Thiazolopyrimidine as Multitarget Inhibitors of Cholinesterases and Monoamine Oxidase A/B for the Treatment of Alzheimer Disease.

In continuation of our previous study to identify multitarget inhibitors of cholinesterases (ChEs) and monoamine oxidase (MAOs) isoforms, we synthesized and evaluated 2-arylidine derivatives of thiazolopyrimidine for the treatment of Alzheimer disease. Three series of compounds with different linker size and target-anchoring functional groups were synthesized. Compounds 34-37 showed excellent to good AChE and BChE inhibition potential at nanomolar to low micromolar concentration. While all the compounds showed excellent MAO-B inhibition and selectivity relative to MAO-A, compounds 25 and 36 emerged as the most potent MAO-B inhibitors of all the series of synthesized compounds with IC50 values of 0.13 µM and 0.10 µM, respectively. Furthermore, kinetic studies of inhibitor 35 showed mixed inhibition mode. Exploration of structure activity relationship (SAR) revealed the role of functionalities and length of linkers on potency. Acute toxicity evaluation showed the safety of tested compounds up to 2000 mg/kg dose. PAMPA-BBB evaluation showed BBB permeability of the tested compounds, while MTT assay performed on neuroblastoma SHSY5Y cells showed that all the tested compounds are non-neurotoxic in the tested concentrations. Docking studies showed a strong correlation with experimental in vitro results via binding orientations and interaction patterns of the synthesized compounds into the binding sites of target enzymes. We have successfully identified safe, non-neurotoxic, and blood brain barrier permeable multitarget lead compounds for the treatment of AD.

Recent developments made in the assessment of the antidiabetic potential of gymnema species - From 2016 to 2020.

BACKGROUND: In traditional herbal medicine, the Gymnema species has been well known for various therapeutic activities such as anti-diabetic, anti-inflammatory, anti-bacterial, anti-arthritic, anti-hyperlipidemic, cytotoxic, and immunostimulatory activities. This review is an effort to analyse all the recent studies done to explore the anti-diabetic potential of traditional Gymnema species. Gymnema sylvestre (Retz.) R.Br. ex Sm. is an important member of the Apocynaceae family that has been used to treat a variety of diseases, the most studied of which is diabetes. This action is mostly due to the pharmacologically active phytoconstituents present in its extract, which include gymnemic acids, triterpenoid saponin glycosides, and so on. Numerous other Gymnema species have also demonstrated a similar pharmacological action. INTRODUCTION: The goal of this study is to give a critical overview of the available data on Gymnema species that are used to treat diabetes. The major goal of this study is to give up-to-date knowledge on ethnopharmacology, botany, pharmacology, and structure-activity relationships of Gymnemaspecies from 2016 to 2020, as well as potential future research. The potential of using medicinal plants for alleviating symptoms of diabetes is recently being recognized. This review aims to summarize the available data and highlight both the potential and shortcomings of using Gymnema therapeutically. This knowledge can further be used to develop more therapeutically effective drugs derived from Gymnema. MATERIALS AND METHODS: Data for Gymnema species was obtained using a mix of several search terms from online databases such as PubMed, SCOPUS, and Europe PMC. Other literature surveys relevant to traditional knowledge, phytochemistry, pharmacology, or structure-activity relationship activity were also used as reference. Several methods by which Gymnema species extracts exert their effects have been investigated, and a summary of the newly discovered chemicals isolated from the plant in the previous five years has been provided. RESULTS: SAR based evaluation has been carried out for a total of 27 pharmacologically active compounds belonging to three species of Gymnema genus (Gymnema sylvestre, Gymnema latifolium, and Gymnema inodorum).These compounds demonstrated the critical significance of plant medicines for diabetes management. Numerous heterocyclic compounds have anti-diabetic action and may serve as a starting point for the design and identification of new diabetes inhibitors. CONCLUSIONS: This study aims to provide researchers with a better understanding of the antidiabetic potential Gymnema species, as well as an outline of prospective future developments. It was concluded after studying the evaluation done in the last 5 years that although extracts of Gymnema have shown good antidiabetic potential, further modifications in the structures could result in the development of more potent and safer compounds.

Fluoxetine and sertraline based multitarget inhibitors of cholinesterases and monoamine oxidase-A/B for the treatment of Alzheimer's disease: Synthesis, pharmacology and molecular modeling studies.

For the potential therapy of Alzheimer's disease (AD), cholinesterases (ChE) and monoamine oxidase (MAO) are key enzymes that regulate the level of acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) and monoamines. The aim of current research is the synthesis of multi-target compounds that can concomitantly inhibit ChEs and MAO. A series of fluoxetine and sertraline hybrids was designed and evaluated as multi-target inhibitors of ChEs and hMAO. In-vitro enzyme inhibition studies demonstrated that a number of compounds displayed excellent inhibition in submicromolar to nanomolar range. However, compounds 17, 22, 38-40 possess excellent concomitant inhibitory activity against ChEs and hMAO-A/B enzymes and thus emerged as optimal multi-target hybrids. In-vivo acute toxicity study showed the safety of synthesized compounds up to 2000 mg/kg dose. The examinations of brain tissue in Swiss albino mice suggested that selected most active MAO-B inhibitors 17 and 22 have a propensity to block the MAO-B activity that could be responsible for their neurodegenerative effect in mice. The in-vitro inhibitory manner of interaction of these multipotent compounds on all four targets were confirmed by molecular docking investigations.

Scale-up fermentation of Escherichia coli for the production of recombinant endoglucanase from Clostridium thermocellum.

Endoglucanase (EC 3.2.1.4) catalysing the hydrolysis of ß-1.4-glycosidic linkage of cellulose molecules is an enzyme of tremendous industrial importance. The present study describes a response surface methodology based predicted model to deduce a set of fermentation conditions for optimum growth and activity of recombinant endoglucanase in E. coli BL21 (DE3). Numerous significant parameters including fermentation media composition, temperature (Celsius), pH and agitation rate (rpm) were analysed systemically by employing central composite design. This effort reports highly efficient recombinant endoglucanase overproduction (6.9 gl-1 of biomass) with 30% expression by E. coli in modified M9NG media incubated at 37 °C and pH 7 agitated at 200 rpm. Addition of 3 mM glucose and 24 mM glycerol in the M9NG media has shown positive effect on the enzyme yield and activity. The CMCase activity experimentally estimated was found to be 1185 U/mg with the optimized parameters. The outcomes of both the responses by the predicted quadratic model were found in consensus with the obtained values. Our results well depicted the favourable conditions to further scale-up the volumetric yield of other relevant recombinant enzymes and proteins.

Effects of urolithins on obesity-associated gut dysbiosis in rats fed on a high-fat diet.

Obesity is a global health concern associated with the dysbiosis of intestinal microbial composition. In this study, we investigated the potentials of urolithin A (Uro-A) and urolithin B (Uro-B), two gut microbiota-derived metabolites of ellagitannins, in reducing body weight gain through the modulation of the gut microbiota. We established a high-fat diet (HFD)-induced obesity model in rats that were later administered with either 2.5 mg/kg of Uro-A or Uro-B. Serum biochemical parameters were quantified, and changes in the composition of the gut microbial community were analysed using 16S rDNA gene sequencing. Our results showed that the urolithins significantly decreased the body weight in HFD-fed rats and restored serum lipid profile. The taxonomic analysis showed that both Uro-A and Uro-modulated gut microbes related to body weight, dysfunctional lipid metabolism and inflammation. Overall, our results suggest that Uro-A and Uro-B possess anti-obesity properties, which may be related to the modulation of the gut microbial composition.

Autism - A Comprehensive Array of Prominent Signs and Symptoms.

BACKGROUND: Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by multiple psychological and physiological impairments in young children. According to the recent reports, 1 out of every 58 newly-born children is suffering from autism. The aetiology of the disorder is complex and poorly understood, hindering the adaptation of targeted and effective therapies. There are no well- established diagnostic biomarkers for autism. Hence the analysis of symptoms by the pediatricians plays a critical role in the early intervention. METHODS: In the present report, we have emphasized 24 behavioral, psychological and clinical symptoms of autism. RESULTS: Impaired social interaction, restrictive and narrow interests, anxiety, depression; aggressive, repetitive, rigid and self-injurious behavior, lack of consistency, short attention span, fear, shyness and phobias, hypersensitivity and rapid mood alterations, high level of food and toy selectivity; inability to establish friendships or follow the instructions; fascination by round spinning objects and eating non-food materials are common psychological characteristics of autism. Speech or hearing impairments, poor cognitive function, gastrointestinal problems, weak immunity, disturbed sleep and circadian rhythms, weak motor neuromuscular interaction, lower level of serotonin and neurotransmitters, headache and body pain are common physiological symptoms. CONCLUSION: A variable qualitative and quantitative impact of this wide range of symptoms is perceived in each autistic individual, making him/her distinct, incomparable and exceptional. Selection and application of highly personalized medical and psychological therapies are therefore recommended for the management and treatment of autism.

Hepatoprotective Effects of (-) Epicatechin in CCl4-Induced Toxicity Model Are Mediated via Modulation of Oxidative Stress Markers in Rats.

OBJECTIVE: (-) Epicatechin (EP) is a naturally occurring antioxidant flavonoid found in some green plants. The current study was designed to evaluate the potential role of antioxidant mechanisms in the hepatoprotective properties of EP using the carbon tetrachloride (CCl4)-induced acute liver injury model. MATERIALS AND METHODS: Rats (n = 7 per group) were divided into five groups including control group, (-) epicatechin group (20 mg·kg-1 body weight), CCl4 group (1 mL-1 body weight), CCl4-EP treatment group, and CCl4-silymarin (SILY) group. The levels of enzymes including hepatic malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione S-transferase (GST), nitric oxide synthase (NOS), glutathione peroxidase (GPx), and cytochrome P450 (CYP450) were analyzed via enzyme-linked immunosorbent assay (ELISA). Histological studies were performed on all groups to assess the regenerative effects of test sample and compare it with the control group. RESULTS: Test compound EP and standard drug silymarin (SILY) considerably reduced liver function enzyme levels in the blood, which were raised by CCl4 administration, and increased serum albumin and total protein (TP) concentrations. The hepatic malondialdehyde (MDA) level was considerably declined, whereas glutathione (GSH), catalase (CAT), glutathione S-transferase (GST), nitric oxide synthase (NOS), glutathione peroxidase (GPx), and cytochrome P450 (CYP450) levels were upregulated in the EC-treated groups. The hepatoprotective results of the study were further confirmed via the histological assessments, which indicated a regeneration of the damaged hepatic tissue in treated rats. CONCLUSIONS: The results of this study revealed a significant protective efficacy of EP against CCl4-induced liver injury, which was potentially mediated via upregulation of antioxidant enzymes and direct scavenging effects of the compound against free radicals.

In vitro antiglycation and antioxidant properties of benzophenone thiosemicarbazones.

Fifteen benzophenone thiosemicarbazones were synthesized and their in vitro antiglycation activity was evaluated. The most active compound 2 (IC50 = 118.15±2.41µM) showed two folds potent activity than the standard, rutin (IC50 = 294.5±1.5µM). Compounds 1 and 3-7 showed good to moderate antiglycation activity in the range of 204.14 - 488.54µM. These compounds were also evaluated for antioxidant activity. Their structure-activity relationships have been developed. The results reveal the potential of these compounds as leads for further studies towards the development of antidiabetic drugs.

Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet.

BACKGROUND: Urolithins are gut microbiota-derived polyphenol metabolites, produced following the consumption of pomegranate, berries, and nuts. Recent studies have shown the potentials of these metabolites on reducing triglycerides accumulation in cultured hepatocytes and adipocytes. In this study, we investigated the ability of both urolithin A (Uro-A) and urolithin B (Uro-B) to attenuate obesity and associated symptoms in a high-fat diet-induced obesity model in rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups. Group 1 was fed on a normal diet while groups 2, 3, and 4 were fed on a high-fat diet for 10 weeks. After this, groups 3 and 4 were treated with 2.5mg/kg body weight of Uro-A and Uro-B intraperitoneally, respectively. Body weight, serum lipid profile, hepatic antioxidant activity, hepatic lipid accumulation, fecal lipid content, and the expressions of genes involved in lipogenesis and hepatic ER stress were quantified. RESULTS: Indeed, a high-fat diet resulted in increased body weight, visceral adipose tissue mass, and oxidative stress in rats. However, treatment with both Uro-A and Uro-B decreased body weight and visceral adipose tissue mass. These metabolites restored hepatic antioxidant capacity and decreased lipid accumulation in addition to an increase in fecal fat excretion. Moreover, both Uro-A and Uro-B treatment downregulated the expression of LXRα and SREBP1c; involved in de novo lipogenesis while upregulating PPARα expression for increased fatty acid oxidation. Furthermore, Uro-A and Uro-B decreased the expression of PERK and IRE1α; which are involved in hepatic ER stress. Taken together, our results showed the potentials of Uro-A and Uro-B in mitigating obesity symptoms and they could thus provide promising roles in the future as functional anti-obesity candidates.

Thymoquinone and Difluoromethylornithine (DFMO) Synergistically Induce Apoptosis of Human Acute T Lymphoblastic Leukemia Jurkat Cells Through the Modulation of Epigenetic Pathways.

Thymoquinone (TQ), a natural anticancer agent exerts cytotoxic effects on several tumors by targeting multiple pathways, including apoptosis. Difluoromethylornithine (DFMO), an irreversible inhibitor of the ornithine decarboxylase (ODC) enzyme, has shown promising inhibitory activities in many cancers including leukemia by decreasing the biosynthesis of the intracellular polyamines. The present study aimed to investigate the combinatorial cytotoxic effects of TQ and DFMO on human acute T lymphoblastic leukemia Jurkat cells and to determine the underlying mechanisms. Here, we show that the combination of DFMO and TQ significantly reduced cell viability and resulted in significant synergistic effects on apoptosis when compared to either DFMO or TQ alone. RNA-sequencing showed that many key epigenetic players including Ubiquitin-like containing PHD and Ring finger 1 (UHRF1) and its 2 partners DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) were down-regulated in DFMO-treated Jurkat cells. The combination of DFMO and TQ dramatically decreased the expression of UHRF1, DNMT1 and HDAC1 genes compared to either DFMO or TQ alone. UHRF1 knockdown led to a decrease in Jurkat cell viability. In conclusion, these results suggest that the combination of DFMO and TQ could be a promising new strategy for the treatment of human acute T lymphoblastic leukemia by targeting the epigenetic code.

COVID-19: Prospective Challenges and Potential Vaccines.

CONTEXT: RNA viruses exhibit an extraordinary ability to evolve in a changing environment and to switch from animal hosts to humans. The ongoing COVID-19 pandemic, recognized as a respiratory disease, is an example of zoonotic transmission of the RNA virus known as SARS-CoV-2. The development and regulatory approval of a vaccine against SARS-CoV-2 pose multiple preventive and therapeutic challenges, especially during an ongoing pandemic. OBJECTIVE: The review intended to examine the challenges and recent achievements in the development of vaccine candidates against COVID-19. DESIGN: The research team performed a literature review, searching relevant and up to date information from the literature. The sources of data included Google Scholar, PubMed, NCBI, and Yahoo. The search terms used were COVID-19 challenges, SARS-CoV-2 prospective challenges, RNA viruses adoptability, host switching by RNA viruses, COVID-19 vaccines. SETTING: The study took place at the digital libraries of contributing institutions. The data was combined, selected for further analysis and manuscript preparation at King Abdulaziz University. RESULTS: RNA viruses with high rate of genome alterations and evolution have better chances to survive in the adverse environmental conditions by adopting the alternate host species. The recent epidemics such as SARS, MERS, and COVID-19 are examples of zoonotic transmission of RNA viruses from animal species to the humans. However, the mechanisms involved in the switching-on to new host species need further investigations to control the zoonotic transmissions in near future. As of April 2020, 115 candidate vaccines were being evaluated; 78 of them had been found to be active, and a few of them are in Phase I trials. In the development of different types of vaccine candidates against COVID-19, multiple international pharmaceutical and biotechnology companies are involved. CONCLUSIONS: Emerging and re-emerging pathogenic RNA viruses pose a serious threat to human health. Little is known about the human-host adoptive mechanism for zoonotic transmission. Deep insights into the molecular mechanism responsible for the switching of animal or bird viruses to humans could provide target molecules or events to prevent such transmissions in the near future. Fast development and approval of efficacious and safe vaccines is key to the effort to provide preventive measures against COVID-19 and future viruses. However, the development and availability of a vaccine candidate is a time-consuming process and often can't be completed during an epidemic. Currently, several types of vaccines are under development, and most of them won't realistically be available in time for the present COVID-19 pandemic.

Intelligent Machine Learning Approach for Effective Recognition of Diabetes in E-Healthcare Using Clinical Data.

Significant attention has been paid to the accurate detection of diabetes. It is a big challenge for the research community to develop a diagnosis system to detect diabetes in a successful way in the e-healthcare environment. Machine learning techniques have an emerging role in healthcare services by delivering a system to analyze the medical data for diagnosis of diseases. The existing diagnosis systems have some drawbacks, such as high computation time, and low prediction accuracy. To handle these issues, we have proposed a diagnosis system using machine learning methods for the detection of diabetes. The proposed method has been tested on the diabetes data set which is a clinical dataset designed from patient's clinical history. Further, model validation methods, such as hold out, K-fold, leave one subject out and performance evaluation metrics, includes accuracy, specificity, sensitivity, F1-score, receiver operating characteristic curve, and execution time have been used to check the validity of the proposed system. We have proposed a filter method based on the Decision Tree (Iterative Dichotomiser 3) algorithm for highly important feature selection. Two ensemble learning algorithms, Ada Boost and Random Forest, are also used for feature selection and we also compared the classifier performance with wrapper based feature selection algorithms. Classifier Decision Tree has been used for the classification of healthy and diabetic subjects. The experimental results show that the proposed feature selection algorithm selected features improve the classification performance of the predictive model and achieved optimal accuracy. Additionally, the proposed system performance is high compared to the previous state-of-the-art methods. High performance of the proposed method is due to the different combinations of selected features set and Plasma glucose concentrations, Diabetes pedigree function, and Blood mass index are more significantly important features in the dataset for prediction of diabetes. Furthermore, the experimental results statistical analysis demonstrated that the proposed method would effectively detect diabetes and can be deployed in an e-healthcare environment.

Molecular characterisation in tongue squamous cell carcinoma reveals key variants potentially linked to clinical outcomes.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a highly aggressive malignancy characterized by frequent recurrence, poor survival with relatively few therapeutic options due to the late diagnosis in many cases. OBJECTIVES: Understanding the molecular pathways underlying OTSCC tumourigenesis and the discovery of diagnostic and/or prognostic biomarkers. METHODS: We performed high-throughput mutational analysis of 44 OTSCC formalin-fixed paraffin-embedded (FFPE) cases using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™platform. We determined the frequency of human papilloma virus (HPV) using PCR and Epstein bar virus (EBV) positivity using immunohistochemistry. As a control for EBV infection we screened matched non-tumourous tissues. RESULTS: Sequencing analysis identified missense, nonsense and frameshift mutations in TP53 (66%), PIK3CA (27%), CDKN2A (25%), EGFR (18%), and PTEN (14%). Interestingly, no significant associations were found between damaging mutations and clinicopathological data. A total of 10/44 of the OTSCC samples (23%) tested was positive for HPV18 DNA. OTSCC patients with positive HPV infection had worse overall survival compared to HPV-negative cases as determined by Kaplan-Meier survival (p= 0.023). Furthermore, EBNA1 expression showed a strong tumour-enriched expression pattern in 20 out of 21 samples (95%) in the epithelial compartments of the tissues analysed. CONCLUSIONS: Taken together, this study highlights that the two most common events in OTSCC are TP53 mutations and EBV positivity. Helping to understand the contribution of TP53 mutations and EBV infection events could serve as useful biomarkers for OTSCC.

Metabolic differentiation and quantification of gymnemic acid in Gymnema sylvestre (Retz.) R.Br. ex Sm. leaf extract and its fermented products.

INTRODUCTION: Gymnemagenin is the bioactive metabolite found in Gymnema sylvestre leaves and possesses different therapeutic potential. Due to its lower abundance and higher market potential, gymnemagenin was obtained from chemical conversion and bacterial biotransformation. OBJECTIVE: To obtain the probiotic-based fermentative conversion of gymnemic acid-enriched G. sylvestre leaf extract to gymnemagenin-containing nutraceuticals and its metabolites based chromatographic comparison. MATERIAL AND METHODS: Gymnema sylvestre leaves were extracted through soxhalation, and the extract was prepared and characterised. Gymnemic acid was fermented, separately, by Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium bifidum, and by their mix co-culture. The fermented materials were analysed for their gymnemagenin content, antioxidant potential, antidiabetic potential, and metabolomics analysis. RESULTS: Extraction yielded about 35% w/w of raw plant material, and 8.5% was found to be as total saponin content. Extract at higher concentration (≥ 5%, w/v) significantly altered the growth behaviour of probiotics. High-performance thin-layer chromatography (HPTLC) based quantification of gymnemagenin revealed that a maximum increase of 95.5% gymnemagenin was found in extract incubated with B. bifidum followed by mix co-culture containing (B. bifidum, L. casei, and L. rhamnosus), L. casei, and L. rhamnosus. However, liquid chromatography mass spectrometry (LC-MS) analysis resulted in the identification of a total of 56 metabolites. CONCLUSION: Chromatographically profiled, and probiotic-based fermented G. sylvestre leaves can be used as a potent nutraceutical for diabetes and other metabolic disorders.

WYE-354 restores Adriamycin sensitivity in multidrug-resistant acute myeloid leukemia cell lines.

Multidrug resistance (MDR) is a major reason for the failure of acute myeloid leukemia (AML) therapy. Agents that reverse MDR and sensitize AML cells to chemotherapy are of great clinical significance. The present study developed Adriamycin (Adr)­resistant cell lines, namely K562/Adr200 and K562/Adr500, which exhibited MDR. The upregulation of ATP­binding cassette subfamily B member 1 (ABCB1) was confirmed as the mechanism of resistance by reverse transcription­quantitative polymerase chain reaction and western blot analyses. Subsequently, the role of the mammalian target of rapamycin (mTOR) kinase inhibitor, WYE­354, in sensitizing the K562/Adr200 and K562/Adr500 cell lines to Adr was evaluated. At sub­cytotoxic concentrations, WYE­354 increased Adr cytotoxicity in the K562/Adr200 and K562/Adr500 cells. WYE­354 restored Adr sensitivity in the resistant cells by inhibiting ABCB1­mediated substrate efflux, thereby leading to an accumulation of Adr, an increase in Adr­mediated G2/M cell cycle arrest and the induction of apoptosis. Furthermore, WYE­354 stimulated the ATPase activity of ABCB1, which was consistent with in silico predictions using a human ABCB1 mouse homology model, indicating that WYE­354 is a potent substrate of ABCB1. WYE­354 did not regulate the expression of ABCB1 at the concentrations used in the present study. These findings indicate that WYE­354 may be a competitive inhibitor of ABCB1­mediated efflux and a potential candidate in combination with standard chemotherapy for overcoming MDR. Further clinical investigations are warranted to validate this combination in vivo.

Osteoporosis knowledge and awareness among university students in Saudi Arabia.

Awareness and knowledge about any disease is the first step to prevent and treat it, so this study evaluates osteoporosis awareness and knowledge in university students. Our results showed a high awareness and good knowledge of osteoporosis. Females were better informed than males. Knowledge increased with increasing education level. PURPOSE: Osteoporosis is a worldwide health problem, including Saudi Arabia where vitamin D deficiency is common. Prevention of osteoporosis must begin by increasing awareness of the disease from a young age. This study aimed to assess awareness and knowledge of osteoporosis among young adults (18-30 years) attending Saudi universities, exploring the relationship between education and gender and the sources of information in this age group. METHODS: A cross-sectional survey was conducted in 337 students (176 females; 161 males) randomly selected from four Saudi universities during January-December 2017. Education level ranged from preparatory year to undergraduate and postgraduate levels. A self-reported questionnaire was designed to assess awareness and knowledge of osteoporosis across several domains, including risk factors for the disease, prevalence, symptoms, prevention, and treatment. RESULTS: Overall, 92% of students had some awareness of osteoporosis through a variety of sources, predominantly via friends. Just over half of all students had a good or high knowledge level overall (53.4 ± 16.6%). Knowledge score correlated with education (r2 = 0.28) and gender (r2 = 0.27); p < 0.0001. Females were better informed than males (57.7 ± 15.4% vs 48.8 ± 16.8%; p < 0.0001). Knowledge increased with increasing education level (preparatory year (47.8 ± 15.3%), undergraduate (53.5 ± 16.5%), and postgraduate (61.8 ± 15.8%); all p < 0.0001). CONCLUSION: Knowledge of osteoporosis was good among university students in Saudi Arabia, higher in females and with increasing years of education. Overall, students were more knowledgeable about risk factors compared to other aspects such as symptoms, prevention, or treatment of osteoporosis.