Estimation of Interleukin-1ß Promoter (-31 C/T and -511 T/C) Polymorphisms and Its Level in Coronary Artery Disease Patients.

Interleukin-1ß (IL-1ß) is an inflammation-causing cytokine that exerts several unique biological effects and could lead to future adverse events of CAD. The piece of work presented herein is aimed at investigating possible association of IL-1ß levels to its polymorphic site viz. -511 and -31 at promoter region in Saudi CAD patients. The study included 155 confirmed CAD patients and 80 healthy control individuals both men and women. Concentration of IL-1ß in the patients' serum was measured by ELISA method. For single nucleotide polymorphism (SNP) analysis, sanger method of DNA sequencing was followed. We observed variable numbers of SNPs at -31 C/T and -511 T/C promoter regions in Saudi patients suffering from CAD in comparison to the control set of individuals. However, the changes in the number of SNP-hotspots were determined to be non-significant with reference to the control set. The haplotype analysis at -31 and -511 also did not show any significant changes between control and CAD patients. Moreover, serum IL-1ß levels were observed to be expressively higher in patients suffering from CAD (P < 0.001) and its associated complications viz. STEMI (P < 0.001), NSTEMI (P < 0.001), and UA (P < 0.001). Our study provides the status of SNPs at IL-1ß promoter in Saudi population. As per our information, ours is the first article that shows the genetic diversity in IL-1ß promoters and its level in the Saudi CAD patients. J. Cell. Biochem. 118: 2977-2982, 2017. © 2017 Wiley Periodicals, Inc.

Assessment of IL-18 Serum Level and Its Promoter Polymorphisms in the Saudi Coronary Artery Disease (CAD) Patients.

The purpose of the current study was to find out the possible changes polymorphic site at the promoter region of IL-18 gene in Saudi CAD patients. We have also measured serum IL-18 level to find out, the likely association between its level and polymorphic site. The present study included total 197 subjects (98 confirmed CAD patients both men and women and 99 healthy control individuals). Serum concentration of IL-18 was measured by enzyme linked immuno-sorbent assay. For SNPs analysis, sanger method of DNA sequencing was followed. We observed variable numbers of SNPs at -137 C/G, -607 A/C, and -656 T/G promoter sites in our studied samples. However, the observed changes in the number of SNP hotspots were found to be non-significant compared with control. IL-18 level was found to be significantly (P < 0.001) elevated in CAD patients compared with control individuals. The highest rise of around 36% (P < 0.001) in IL-18 level was recorded in unstable angina (UA) patients. Moreover, the group belonging to UA and non-ST segment elevation myocardial infarction (NSTEMI) showed only 6% rise. On the basis of our result, inflammation seems to have a role in the pathogenesis of CAD but not leading to the significant changes at the genetic level. J. Cell. Biochem. 118: 1849-1854, 2017. © 2017 Wiley Periodicals, Inc.

A putative association of interleukin-10 promoter polymorphisms with cardiovascular disease.

Interleukin-10 (IL-10) is an anti inflammatory cytokine involved in the ongoing coronary inflammation and related patho-physiological processes. The piece of work presented herein is aimed at investigating possible association of polymorphisms in IL-10 promoter with Saudi cardiovascular disease (CVD) patients. The study included 80 confirmed CVD patients with diabetes and 75 healthy control individuals both men and women. Concentration of IL-10 in the serum samples were measured by ELISA method. For single nucleotide polymorphism (SNP) analysis, Sanger method of DNA sequencing was followed. The IL-10 level was found to be significantly elevated in CVD patients (P < 0.001) and its associated complications viz. ST-elevation myocardial infarction [STEMI] (P <0.01), non ST-elevation myocardial infarction [NSTEMI] (P < 0.05), and unstable angina [UA] (P < 0.001). We also observed a significant association between polymorphisms in IL-10 promoter at -1082 and -819 locus with Saudi CVD patients. Moreover, at -1082 A/G locus, AA haplotype was found to be less frequent in the CVD patients compared with control individuals. On the other hand, highly significant rise in heterozygous (A/G genotype) condition was observed in patient samples compared with control ones (P < 0.001). Similarly, the genotypic frequencies at -819 C/T locus were also found to be significantly associated (P < 0.001) with CVD patients compared with control individuals. Our study provides the status of polymorphism in IL-10 promoter and its association with CVD risk in Saudi population. As per our information, ours is the first article that shows the genetic diversity in IL-10 promoters and its level in the Saudi CVD patients. © 2017 IUBMB Life, 69(7):522-527, 2017.

Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery Disease.

BACKGROUND: Natural killer (NK) cells are the potential modulators of inflammatory reactions that exert several unique biological effects and could lead to future adverse events of coronary artery disease (CAD). HYPOTHESIS: The purpose of this study was to find out the possible association of modulation in NK cell, TNK cells, T cells, B cells, and tumor necrosis factor alpha (TNF-α) in CAD patients and various forms of myocardial infarction. METHODS: The present study included total 190 subjects (98 confirmed CAD patients both men and women and 92 healthy control individuals). Serum concentration of TNF-α was measured by ELISA method. For the measurement of various immune cells, viz., NK cell, TNK cells, T cells, and B cells, flow-cytometric analysis was performed. RESULTS: A significant reduction by 15% (P < 0.001) in CD16/CD56 NK cells was observed in CAD patients. Moreover, non-ST segment elevation myocardial infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI), unstable angina (UA), and combined UA + NSTEMI group also showed a significant decline in NK cells compared with control individuals. CD16/CD56/CD3 TNK cells showed a significant reduction in CAD, NSTEMI, STEMI, and UA categories. However, UA + NSTEMI group did not show any significant change in TNK cells. On the other hand, the level of TNF-α was found to be significantly elevated in CAD, STEMI, and UA groups. NSTEMI and combined UA + NSTEMI group did not show any significant change in TNF-α level. CONCLUSION: Current study provides an insight toward the association of immune cells and inflammation with CAD.

Assessment of genetic diversity in IL-6 and RANTES promoters and their level in Saudi coronary artery disease patients.

BACKGROUND: The present study consisted of a total of 200 subjects (100 confirmed coronary artery disease (CAD) patients), both men and women, and 100 healthy control individuals. METHODS: Serum concentration of IL-6 and RANTES were measured by enzyme-linked immunosorbent assay kit. For SNPs analysis, sanger method of DNA sequencing was followed. RESULTS: We observed variable numbers of SNP sites at -174 G/C, -572 G/C, and -597 G/A in IL-6 and -28 C/G and -109 C/T in RANTES promoters in CAD patients compared with control individuals. However, the observed changes in the number of SNPs were found to be non-significant compared with control individuals. The IL-6 level was found to be significantly (P<.001) elevated in CAD patients compared with control. Moreover, RANTES serum level did not show any significant change in CAD patients. CONCLUSION: Based on our result, it is quite clear that inflammation has a role in the pathogenesis of CAD but does not lead to significant changes at the genetic level in our population. As far as our knowledge goes, this is the first report that shows the genetic diversity in IL-6 and RANTES promoters and their respective levels in Saudi CAD patients.

Sugiol Suppresses the Proliferation of Human U87 Glioma Cells via Induction of Apoptosis and Cell Cycle Arrest.

The diterpenoid, sugiol, has been reported to exert anticancer effects against a number of human cancers. However, the anticancer effects of sugiol have not been evaluated against the human glioma cells. The present study was designed to examine the effects of sugiol on the proliferation of human U87 glioma cells. The results showed that sugiol significantly (P < 0.05) suppressed the viability of the U87 cells in a concentration dependent manner and exhibited an IC50 value of 15 µM. On the other hand, the growth inhibitory effects of sugiol were minimal on the normal human astrocytes. Acridine orange and ethidium bromide staining (AO/EB) staining revealed that sugiol induces apoptosis which was further confirmed by Western blot analysis, wherein upregulation of Bax and downregulation of Bcl-2 were observed in U87 cells. Flow cytometry showed that sugiol causes cell cycle arrest at the G 0/G 1 stage. The relative percentage of G1 phase was found to be increased from 26.58% at 0 µM to 70.96% at 30 µM sugiol. Taken together, the results suggest sugiol inhibits the growth of glioma cells and may prove to be a lead molecule in the management of human glioma.

A literature perspective on the pharmacological applications of yohimbine.

Introduction: Phytochemicals have garnered much attention because they are useful in managing several human diseases. Yohimbine is one such phytochemical with significant pharmacological potential and could be exploited for research by medicinal chemists. It is an indole alkaloid obtained from various natural/synthetic sources.Aims and Results: The research on yohimbine started early, and its use as a stimulant and aphrodisiac by humans has been reported for a long time. The pharmacological activity of yohimbine is mediated by the combined action of the central and peripheral nervous systems. It selectively blocks the pre and postsynaptic α2-adrenergic receptors and has a moderate affinity for α1 and α2 subtypes. Yohimbine also binds to other behaviourally relevant monoaminergic receptors in the following order: α-2 NE > 5HT-1A>, 5HT-1B > 1-D > D3 > D2 receptors.Conclusion: The current review highlights some significant findings that contribute to developing yohimbine-based drugs. It also highlights the therapeutic potential of yohimbine against selected human diseases. However, further research is recommended on the pharmacokinetics, molecular mechanisms, and drug safety requirements using well-designed randomized clinical trials to produce yohimbine as a pharmaceutical agent for human use.Key MessagesYohimbine is a natural indole alkaloid with significant pharmacological potential.Humans have used it as a stimulant and aphrodisiac from a relatively early time.It blocks the pre- and postsynaptic α2-adrenergic receptors that could be exploited for managing erectile dysfunction, myocardial dysfunction, inflammatory disorders, and cancer.

Chemical profile and therapeutic potentials of Xylocarpus moluccensis (Lam.) M. Roem.: A literature-based review.

ETHNOPHARMACOLOGICAL RELEVANCE: Historically, mangrove plants are among the potential sources of foods and remedies for humans living in the forests and nearby communities. Xylocarpus moluccensis (Lam.) M. Roem., an important mangrove medicinal plant, has been traditionally used for many purposes such as treatment of fever, dysentery, diarrhea, swelling, and abdominal disorders. The aim of the present work was to summarize the chemical reports and biological activities of the mangrove medicinal plant X. moluccensis based on information collected from different databases. MATERIALS AND METHODS: An up-to-date search (till Aug 2019) was carried out in databases such as PubMed, Science Direct, Google Scholar, and various patient offices (e.g., WIPO, CIPO, USPTO) using the keywords: 'Xylocarpus moluccensis', and/or paired with 'ethnobotanical use', and 'phytochemical'. In vitro, ex vivo, or in vivo studies were included. RESULTS: Findings suggest that X. moluccensis contains various important minerals and phytochemicals, where flavonoids, terpenes and terpenoids are the most prominent isolated phyto-constituents of X. moluccensis. Extracts/fractions or isolated compounds from this plant possess diverse biological activities, including anti-inflammatory, anti-microbial, antineoplastic, anti-diarrheal, insecticidal, anti-feedant, neuropharmacological (e.g., central nervous system depressant), anti-atherosclerotic, and lipid-lowering activity. Only one report suggests that the methanol and aqueous extracts of this plant did not exert cytotoxic effects on normal mouse fibroblast cells. However, no clinical studies were reported. CONCLUSIONS: Taken all together, X. moluccensis may be one of the best sources of pharmacologically active lead compounds. More research, however, is necessary to establish the safety and efficacy, and its toxicogenetic effects in animal models.

The Use of Azoles Containing Natural Products in Cancer Prevention and Treatment: An Overview.

BACKGROUND & OBJECTIVE: Cancer is one of the leading causes of death worldwide. In view of ever increasing number associated with cancer related death, there is an urgent need to find out a novel compound especially of natural origin (better efficacy, less or non-toxic and cost effective) that could serve against the treatment of all forms of cancer. Currently, available treatment options related to cancer have their certain limitations especially in the case of solid tumors. METHOD: In search of the natural anticancer compound, alkaloids, in general, have been exploited by the scientist working in this field of research. Among these alkaloids, azoles (secondary metabolite) have been significantly highlighted in literature because of their anticancer potential and better efficacy against various forms of cancer. RESULTS: Their mechanism of action includes induction in the cleavage of poly-ADP ribose polymerase (PARP), induction of caspase 3 and caspase 9, modulation of nuclear factor kappa B, damage to DNA, cell cycle arrest at G1 and G2/M stage, apoptosis and c-Myb inhibition. In the current article, we have tried to cover various azoles especially from oxazoles, thiazoles and carbazoles class that have been reported for their anticancer potential. CONCLUSION: Based on our article, we believe that, soon, the scientific community will come up with certain azole which will work against cancer at large rather than a specific type of cancer.

An overview on the current status of cancer nanomedicines.

PURPOSE: Cancer remains a significant cause of morbidity and mortality across the globe. A recent report suggests around 14.1 million new cases and 8.2 million cancer-related deaths, which are expected to reach 21.7 million and 13 million by 2030 worldwide, respectively. MATERIALS AND METHODS: Because of highly complex mechanisms of cancer progression, it is important to explore and develop new innovative technologies which are more efficient compared with presently available treatment options. RESULTS: Currently, chemotherapy, radiation and surgery are the most commonly used cancer treatment methods. In the last decade, nanomedicine emerged as an alternative treatment option that uses specific drug-delivery systems, improves efficacy of drugs and reduces detrimental side effects to normal tissues. CONCLUSION: In this review, we have summarized cancer nanomedicines (active and passive drug delivery) available in the market. We have also discussed other nanomedicines that are at different stages of clinical trials.

An Insight on the Pathogenesis and Treatment of Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is a diverse autoimmune disorder, evoked in response to self-immune system that leads to immune complex depositions and organ damage. The exact mechanism of SLE pathogenesis is still unclear but certain genetic and environmental factors have been suggested that could influence its pathogenesis. DISCUSSION: The modulation in B- and T- cell responses and genetic variations could lead to abnormal lymphocyte functions and the production of antibodies against the indigenous proteins and the immune complex depositions. CONCLUSION: The present review highlights the various causatives of SLE, particularly the genetic alteration in B- and T-cell-related proteins. We have also delineated some of the available therapeutic strategies for the treatment of SLE.

Effect of Diterpenes on Hepatic System.

Complication in the hepatic system is a major concern for human being. To control and keep the hepatic system healthy, a number of measures, including drug treatments are considered. Diterpenes are essential oils having promising antioxidant and cytotoxic properties along with their genotoxic and mutagenic effects. These agents are good targets for health promotion, especially in the light of their potential organo-protectivity. We searched in the databases, PUBMED and SCIENCE DIRECT from June 2011 to June 2016 for publishing evidence on diterpenes and their effects on hepatic system. After sorting the data, activity-wise findings are discussed in this current article. The results suggest that diterpenes have hepatoprotectivity property via antioxidant and anti-inflammatory, antimicrobial, anticancer/antitumor, hypolipidemic, anti-apoptosis, autophagic, antimetastasize, anti-proliferating, anti-fibrosis as well as receptor and serum biomarkers mediated pathways. On the other hand, hepatoxic effects of diterpenes are also accounted with cytotoxicity, apoptotic cell death and downregulation of cytochrome P450 systems. A number of important diterpenes have been reported in the literatures that act on the hepatic system. Some of them exert toxic effects on the liver, especially in rodent model. Hence, more extensive researches are recommended that will highlight their mechanism of action on the liver.

Synopsis on the linkage of Alzheimer's and Parkinson's disease with chronic diseases.

Neurodegeneration is the progressive loss of neuronal structure and function, which ultimately leads to neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and Huntington's disease. Even after the recent significant advances in neurobiology, the above-mentioned disorders continue to haunt the global population. Several studies have suggested the role of specific environmental and genetic risk factors associated with these disorders. However, the exact mechanism associated with the progression of these disorders still needs to be elucidated. In the recent years, sophisticated research has revealed interesting association of prominent neurodegenerative disorders such as AD and PD with chronic diseases such as cancer, diabetes, and cardiovascular diseases. Several common molecular mechanisms such as generation of free radicals, oxidative DNA damage, aberrations in mitochondrial DNA, and dysregulation of apoptosis have been highlighted as possible points of connection. The present review summarizes the possible mechanism of coexistence of AD and PD with other chronic diseases.