Screening of Cu4 O3 NPs efficacy and its anticancer potential against cervical cancer.

Cu4 O3 is the least explored copper oxide, and its nanoformulation is anticipated to have important therapeutic potential especially against cancer. The current study aimed to biosynthesize Cu4 O3 nanoparticles (NPs) using an aqueous extract of pumpkin seeds and evaluate its antiproliferative efficacy against cervical cells after screening on different cancer cell lines. The obtained NPs were characterized by different spectroscopic analyses, such as UV-vis, thermogravimetric, energy dispersive X-ray, and Fourier-transform infrared spectroscopy (FTIR). In addition, high-resolution transmission electron microscopes (HR-TEM) were used to observe the morphology of the biosynthesized NPs. The UV-vis spectra showed a peak at around 332 nm, confirming the formation of Cu4 O3 NPs. Moreover, FTIR and TAG analyses identified the presence of various bioactive phytoconstituents that might have worked as capping and stabilization agents and comparative stable NPs at very high temperatures, respectively. The HR-TEM data showed the spherical shape of Cu4 O3 NPs in the range of 100 nm. The Cu4 O3 NPs was screened on three different cancer cell lines viz., Hela, MDA-MB-231, and HCT-116 using cytotoxicity (MTT) reduction assay. In addition, Vero was taken as a normal epithelial (control) cell. The high responsive cell line in terms of least IC50 was further assessed for its anticancer potential using a battery of biological tests, including morphological alterations, induction of apoptosis/ROS generation, regulation of mitochondrial membrane potential (MMP), and suppression of cell adhesion/migration. Vero cells (control) showed a slight decline in % cell viability even at the highest tested Cu4 O3 NPs concentration. However, all the studied cancer cells viz., MDA-MB-231, HCT 116, and HeLa cells showed a dose-dependent decline in cell viability after the treatment with Cu4 O3 NPs with a calculated IC50 value of 10, 11, and 7.2 µg/mL, respectively. Based on the above data, Hela cells were chosen for further studies, that showed induction of apoptosis from 3.5 to 9-folds by three different staining techniques acridine orange/ethidium bromide (AO/EB), 4',6-diamidino-2-phenylindole (DAPI), and propidium iodide (PI). The enhanced production of reactive oxygen species (>3.5-fold), modulation in MMP, and suppression of cell adhesion/migration were observed in the cells treated with Cu4 O3 NPs. The current study obtained the significant antiproliferative potential of Cu4 O3 NPs against the cervical cancer cell line, which needs to be confirmed further in a suitable in vivo model. Based on our results, we also recommend the green-based, eco-friendly, and cost-effective alternative method for synthesizing novel nanoformulation.

Phenolic Acids-Mediated Regulation of Molecular Targets in Ovarian Cancer: Current Understanding and Future Perspectives.

Cancer is a global health concern with a dynamic rise in occurrence and one of the leading causes of mortality worldwide. Among different types of cancer, ovarian cancer (OC) is the seventh most diagnosed malignant tumor, while among the gynecological malignancies, it ranks third after cervical and uterine cancer and sadly bears the highest mortality and worst prognosis. First-line treatments have included a variety of cytotoxic and synthetic chemotherapeutic medicines, but they have not been particularly effective in extending OC patients' lives and are associated with side effects, recurrence risk, and drug resistance. Hence, a shift from synthetic to phytochemical-based agents is gaining popularity, and researchers are looking into alternative, cost-effective, and safer chemotherapeutic strategies. Lately, studies on the effectiveness of phenolic acids in ovarian cancer have sparked the scientific community's interest because of their high bioavailability, safety profile, lesser side effects, and cost-effectiveness. Yet this is a road less explored and critically analyzed and lacks the credibility of the novel findings. Phenolic acids are a significant class of phytochemicals usually considered in the nonflavonoid category. The current review focused on the anticancer potential of phenolic acids with a special emphasis on chemoprevention and treatment of OC. We tried to summarize results from experimental, epidemiological, and clinical studies unraveling the benefits of various phenolic acids (hydroxybenzoic acid and hydroxycinnamic acid) in chemoprevention and as anticancer agents of clinical significance.

Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy.

BACKGROUND: Cancer is a chronic, heterogeneous illness that progresses through a spectrum of devastating clinical manifestations and remains the 2nd leading contributor to global mortality. Current cancer therapeutics display various drawbacks that result in inefficient management. The present study is intended to evaluate the anticancer potential of Cu-Mn bimetallic NPs (CMBNPs) synthesized from pumpkin seed extract against colon adenocarcinoma cancer cell line (HT-29). METHODS: The CMBNPs were biosynthesized by continuously stirring an aqueous solution of pumpkin seed extract with CuSO4 and manganese (II) acetate tetrahydrate until a dark green solution was obtained. The characteristic features of biogenic CMBNPs were assessed by UV-visible spectrophotometry (UV-vis), X-ray powder diffraction (XRD), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A battery of biological assays, viz. neutral red uptake (NRU) assay, in vitro scratch assay, and comet assay, were performed for anticancer efficacy evaluation. RESULTS: The formation of spherical monodispersed bimetallic nanoparticles with an average size of 50 nm was recorded using TEM. We observed dose-dependent cytotoxicity of CMBNPs in the HT-29 cell line with an IC50 dose of 115.2 µg/mL. On the other hand, CMBNPs did not show significant cytotoxicity against normal cell lines (Vero cells). Furthermore, the treatment of CMBNPs inhibited the migration of cancer cells and caused DNA damage with a significant increase in comet tail length. CONCLUSIONS: The results showed substantial anticancer efficacy of CMBNPs against the studied cancer cell line. However, it is advocated that the current work be expanded to different in vitro cancer models so that an in vivo validation could be carried out in the most appropriate cancer model.

Potential of green-synthesized ZnO NPs against human ovarian teratocarcinoma: an in vitro study.

BACKGROUND: Ovarian cancer leads to devastating outcomes, and its treatment is highly challenging. At present, there is a lack of clinical symptoms, well-known sensitivity biomarkers, and patients are diagnosed at an advanced stage. Currently, available therapeutics against ovarian cancer are inefficient, costly, and associated with severe side effects. The present study evaluated the anticancer potential of zinc oxide nanoparticles (ZnO NPs) that were successfully biosynthesized in an ecofriendly mode using pumpkin seed extracts. METHODS AND RESULTS: The anticancer potential of the biosynthesized ZnO NPs was assessed using an in vitro human ovarian teratocarcinoma cell line (PA-1) by well-known assays such as MTT assay, morphological alterations, induction of apoptosis, measurement of reactive oxygen species (ROS) production, and inhibition of cell adhesion/migration. The biogenic ZnO NPs exerted a high level of cytotoxicity against PA-1 cells. Furthermore, the ZnO NPs inhibited cellular adhesion and migration but induced ROS production and cell death through programmed cell death. CONCLUSION: The aforementioned anticancer properties highlight the therapeutic utility of ZnO NPs in ovarian cancer treatment. However, further research is recommended to envisage their mechanism of action in different cancer models and validation in a suitable in vivo system.

Prioritization of bioactive compounds envisaging yohimbine as a multi targeted anticancer agent: insight from molecular docking and molecular dynamics simulation.

Recently, multi-targeted drugs have attracted much attention in cancer therapy where several therapeutic proteins are targeted by a single agent. Using the published scientific literature, we selected sixteen well-known anticancer targets and seven potential phytobioactive chemicals to find a multitargeted compound by screening through molecular docking. The feasible protein-ligand interaction was further predicted by protein-ligand interaction analysis and molecular dynamic simulation. The phytochemical yohimbine exhibited the lowest docking score in the range of -8.3 to -10.0 kcal/mol over other ligands with all the studied protein targets. Molecular interaction data also revealed the feasible binding of yohimbine with all targets. Moreover, the molecular simulation data also confirmed the stability of protein-ligand complexes with three most scored targets viz. ERK2, PARP1 and PIK3α. Based on our results, yohimbine seems to be the most potent compound out of those selected compounds and can be considered as effective lead molecule against the studied target proteins.Communicated by Ramaswamy H. Sarma.

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.

Anticancer potential of yohimbine in drug-resistant oral cancer KB-ChR-8-5 cells.

BACKGROUND: The demand for environmentally friendly and cost-effective plant-based products for the development of cancer therapeutics has been increasing. Yohimbine (α2-adrenergic receptor antagonist) is a stimulant and aphrodisiac used to improve erectile dysfunction. In this study, we aimed to evaluate the anticancer potential of yohimbine in drug-resistant oral cancer KB-ChR-8-5 cells using different biomolecular techniques. METHODS: We estimated the anticancer efficacy of yohimbine using different assays, such as MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell cytotoxicity, cell morphology, cell apoptosis, reactive oxygen species (ROS) formation, and modulation in the mitochondrial membrane potential (MMP). RESULTS: Yohimbine showed a dose-dependent increase in cytotoxicity with a 50% inhibitory concentration (IC50) of 44 µM against KB-ChR-8-5 cancer cell lines. Yohimbine treatment at 40 µM and 50 µM resulted in a considerable change in cell morphology, including shrinkage, detachment, membrane blebbing, and deformed shape. Moreover, at the dose of IC50 and above, a significant induction was observed in the generation of ROS and depolarization of MMP. The possible mechanisms of action of yohimbine underlying the dose-dependent increase in cytotoxicity may be due to the induction of apoptosis, ROS generation, and modulation of MMP. CONCLUSION: Overall, yohimbine showed a significant anticancer potential against drug-resistant oral cancer KB-ChR-8-5 cells. Our study suggests that besides being an aphrodisiac, yohimbine can be used as a drug repurposing agent. However, more research is required in different in vitro and in vivo models to confirm the feasibility of yohimbine in clinics.

Association of IL-6 promoter polymorphism hotspots (- 174G/C and - 572G/C) with cardiovascular disease risk factors.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally, despite the recent advancements in clinical research. Early diagnosis of CVD and prevention of future complications are important for the management of CVD. In the present study, we determined the genotypic linkage of interleukin-6 (IL-6) promoters with the clinical, biochemical, and inflammatory markers of CVD in the Saudi population. MATERIALS AND METHODS: The study consisted of 89 patients (male and female) with CVD who were admitted at the King Abdulaziz university hospital, Jeddah, Saudi Arabia. The biochemical parameters were evaluated using an automated chemistry analyzer, and inflammatory markers were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. For genotypic analysis, Sanger sequencing was performed. We observed a statistically significant association (p < 0.05) between GG (66.29%), GC (30.34%), and CC (3.37%) genotypes at the - 174G/C (rs1800795) hotspot and neopterin levels. However, the genotypes at the - 572G/C (rs1800796) hotspot did not show any association with age, gender, obesity, diabetes, hypertension, dyslipidemia, smoking, and coronary artery status. In addition, no significant association was observed with biochemical and inflammatory markers, namely fasting blood sugar, glycated hemoglobin A1c, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, IL-6, and C-reactive protein. The comparison between different possible genotypic groups and CVD risk factors showed a statistically significant (p < 0.05) association between the male gender and HDL with GG, rs1800795 group vs. GC, rs1800796 group. Similarly, neopterin level was also found to be significantly (p < 0.05) associated with the genotypes GC, rs1800795, and GG, rs1800796. Additionally, the male gender (p < 0.01), age (p < 0.05), serum creatinine (p < 0.001), and neopterin (p < 0.05) were found to be significantly associated with GG, rs1800795 + GG, rs1800796, GC, rs1800795 + GC, and rs1800796 GC. CONCLUSION: The direct association of neopterin level with IL-6 promoter polymorphism at - 174G/C (rs1800795) hotspot indicated the role of inflammation in CVD pathogenesis in the Saudi population.

Concatenation of molecular docking and molecular simulation of BACE-1, γ-secretase targeted ligands: in pursuit of Alzheimer's treatment.

INTRODUCTION: Alzheimer's disease (AD), the most predominant cause of dementia, has evolved tremendously with an escalating frequency, mainly affecting the elderly population. An effective means of delaying, preventing, or treating AD is yet to be achieved. The failure rate of dementia drug trials has been relatively higher than in other disease-related clinical trials. Hence, multi-targeted therapeutic approaches are gaining attention in pharmacological developments. AIMS: As an extension of our earlier reports, we have performed docking and molecular dynamic (MD) simulation studies for the same 13 potential ligands against beta-site APP cleaving enzyme 1 (BACE-1) and γ-secretase as a therapeutic target for AD. The In-silico screening of these ligands as potential inhibitors of BACE-1 and γ-secretase was performed using AutoDock enabled PyRx v-0.8. The protein-ligand interactions were analyzed in Discovery Studio 2020 (BIOVIA). The stability of the most promising ligand against BACE-1 and γ-secretase was evaluated by MD simulation using Desmond-2018 (Schrodinger, LLC, NY, USA). RESULTS: The computational screening revealed that the docking energy values for each of the ligands against both the target enzymes were in the range of -7.0 to -10.1 kcal/mol. Among the 13 ligands, 8 (55E, 6Z2, 6Z5, BRW, F1B, GVP, IQ6, and X37) showed binding energies of ≤-8 kcal/mol against BACE-1 and γ-secretase. For the selected enzyme targets, BACE-1 and γ-secretase, 6Z5 displayed the lowest binding energy of -10.1 and -9.8 kcal/mol, respectively. The MD simulation study confirmed the stability of BACE-6Z5 and γ-secretase-6Z5 complexes and highlighted the formation of a stable complex between 6Z5 and target enzymes. CONCLUSION: The virtual screening, molecular docking, and molecular dynamics simulation studies revealed the potential of these multi-enzyme targeted ligands. Among the studied ligands, 6Z5 seems to have the best binding potential and forms a stable complex with BACE-1 and γ-secretase. We recommend the synthesis of 6Z5 for future in-vitro and in-vivo studies.

Genotyping of interleukins-18 promoters and their correlation with coronary artery stenosis in Saudi population.

BACKGROUND: Complex coronary atherosclerotic lesions often lead to coronary occlusion, clinically represented as a single-vessel disease (SVD) and multivessel disease (MVD). These occlusions could hinder the blood flow in coronary arteries that affects appropriate management of the CVD. The current study intended to genotype interleukin (IL)-18 promoter's hotspots (rs187238, rs1946518, and rs1946519) and their possible association with coronary artery stenosis. MATERIAL AND METHODS: The IL-18 promoter genotyping was performed by the Sanger method along with the examination of biochemical parameters in 125 study subjects categorized into three groups, viz. controls, SVD and MVD. RESULTS: The current study observed a significant association of diabetes, hypertension, and dyslipidemia between the studied group's viz. healthy controls, SVD, and MVD. Fasting blood sugar and glycosylated hemoglobin (HBA1C) were also significantly enhanced from 4.82 vs. 8.01 and 4.33 vs. 8.27, in SVD, and MVD respectively. Despite the visible differences in the pattern of genotypic and allelic expressions, the current study did not show any statistically significant correlation with IL-18 promoter polymorphism at its hotspots with controls, SVD, and MVD subjects. The only exception of the above results was the distribution of allelic frequency at the rs1946519 hotspot, where a significant change (P < 0.05) was observed. CONCLUSION: This study is of additional value to our previous reports, revealing the pattern of genotypes and allelic frequency of IL-18 promoters in a small cohort of Saudi ethnicity. Further investigations on larger sample size are recommended to envisage the presence of functional mutations in the IL-18 gene that could establish or rule out the possible association of IL-18 polymorphism with SVD and MVD.

Identification of novel cardiovascular disease associated metabolites using untargeted metabolomics.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and N1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, N-acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.

Identification of Butyrylcholinesterase and Monoamine Oxidase B Targeted Ligands and their Putative Application in Alzheimer's Treatment: A Computational Strategy.

BACKGROUND: With the burgeoning worldwide aging population, the incidence of Alzheimer's disease (AD) and its associated disorders is continuously rising. To appraise other relevant drug targets that could lead to potent enzyme targeting, 13 previously predicted ligands (shown favorable binding with AChE (acetylcholinesterase) and GSK-3 (glycogen synthase kinase) were screened for targeting 3 different enzymes, namely butyrylcholinesterase (BChE), monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B) to possibly meet the unmet medical need of better AD treatment. MATERIALS AND METHODS: The study utilized in silico screening of 13 ligands against BChE, MAO-A and MAOB using PyRx-Python prescription 0.8. The visualization of the active interaction of studied compounds with targeted proteins was performed by Discovery Studio 2020 (BIOVIA). RESULTS: The computational screening of studied ligands revealed the docking energies in the range of -2.4 to -11.3 kcal/mol for all the studied enzymes. Among the 13 ligands, 8 ligands (55E, 6Z2, 6Z5, BRW, F1B, GVP, IQ6, and X37) showed the binding energies of ≤ -8.0 kcal/mol towards BChE, MAO-A and MAO-B. The ligand 6Z5 was found to be the most potent inhibitor of BChE and MAO-B, with a binding energy of -9.7 and -10.4 kcal mol, respectively. Molecular dynamics simulation of BChE-6Z5 and MAO-B-6Z5 complex confirmed the formation of a stable complex. CONCLUSION: Our computational screening, molecular docking, and molecular dynamics simulation studies revealed that the above-mentioned enzymes targeted ligands might expedite the future design of potent anti-AD drugs generated on this chemical scaffold.

In silico screening of glycogen synthase kinase-3ß targeted ligands against acetylcholinesterase and its probable relevance to Alzheimer's disease.

Alzheimer's disease (AD) is a growing global health concern that affects 10% of the population aged above 65 years. A growing body of evidence indicates that multi-targeted drugs might be useful therapeutic options owing to the heterogeneity of AD pathology. The current study exploited advanced computational biology tools to identify ligands that might display effective binding to two protein targets in the context of AD. The present study used in silico virtual screening of small molecules library to identify effectiveness against two AD targets viz. acetyl cholinesterase (AChE) and glycogen synthase kinase-3ß (GSK-3ß). PyRX-Python prescription with AutodockVina was used to generate binding energy profiles. Further screening was accomplished using SwissADME and molecular interaction studies. The present study obtained 48 ligands (absolute binding energy >8 kcal/mol), by virtual screening of 100 ligands. Among those, 13 ligands (BRW, 6VK, 6Z5, SMH, X37, 55E, 65 A, IQ6, 6VL, 6VM, F1B, 6Z2 and GVP) were selected based on blood brain barrier (BBB) permeability, acceptable ADME properties as well as their molecular interaction profiles with the aforementioned AD-targets. The present study has predicted certain molecules that appear worthy to be tested for effectiveness against two AD targets, namely AChE and GSK-3ß. However, the results warrant further wet laboratory validation, as computational studies are merely predictive in nature. This approach might be useful for future treatment of AD.Communicated by Ramaswamy H. Sarma.

Nanoencapsulated dietary polyphenols for cancer prevention and treatment: successes and challenges.

Many dietary polyphenols have been investigated for their therapeutic potential either as single agents or in combinations. Despite the significant anticancer potential of these polyphenols in in vitro cell culture and in vivo animal models, their clinical applications have been limited because of challenges such as ineffective systemic delivery, stability and low bioavailability. Nanoencapsulation of these polyphenols could prolong circulation, improve localization, enhance efficacy and reduce the chances of multidrug resistance. This review summarized the use of various polyphenols especially epigallocatechin gallate, quercetin, curcumin and resveratrol as nanoformulations for cancer prevention and treatment. Despite some success, more research is warranted to design a nanoencapsulated combination of polyphenols, effective in in vitro, in vivo and human systems.

Association of autoimmunity and cancer: An emphasis on proteolytic enzymes.

Cancer and autoimmune diseases are the two devastating conditions that together constitute a leading health problem worldwide. The rising burden of these disorders in the developing world demands a multifaceted approach to address the challenges it poses. Understanding the root causes and specific molecular mechanisms by which the progression of the diseases takes place is need of the hour. A strong inflammatory background and common developmental pathways, such as activation of immune cells, proliferation, increased cell survival and migration which are controlled by growth factors and inflammatory cytokines have been considered as the critical culprits in the progression and complications of these disorders. Enzymes are the potential immune modulators which regulate various inflammatory events and can break the circulating immune complexes via macrophages production. In the current manuscript, we have uncovered the possible role of proteolytic enzymes in the pathogenesis and progression of cancer and autoimmune diseases. In the light of the available scientific literature, we advocate in-depth comprehensive studies which will shed light towards the role of proteolytic enzymes in the modulation of inflammatory responses in cancer and autoimmune diseases together.

Association of Plasma Fibrinogen Level with Insulin Resistance in Angiographically Confirmed Coronary Artery Disease Patients.

Fibrinogen is an important coagulation factor that plays a key role in thrombus formation. The co-existence of CAD, insulin resistance (IR) and coagulation incongruity are believed to exacerbate the existing condition towards more lethal pathological events.The purpose of current study was to find out a possible association between fibrinogen and IR in CAD patients. The study population consist of 135 participants; 82 angiographically confirmed CAD patients who visited the outpatient department at King Abdulaziz University Hospital (KAUH), Jeddah and 53 healthy control individuals. Peripheral blood samples were collected from CAD patients and healthy control individuals. Various biochemical parameters such as complete blood count, C-reactive protein (CRP), glycosylated hemoglobin (HbA1c), insulin, C-peptide, lipid profile, platelet, partial thromboplastin time (PTT), fibrinogen and D-dimer levels were measured by the use of different analytical methods. Calculation of homeostasis model assessment (HOMA) and non-HDL were done by using online tools. Among the studied parameters, majority of the conventional risk factors were found to be significantly increased in CAD patients compared with control individuals. Different coagulation components such as fibrinogen (223.8 vs. 394 mg/dL), D-dimer (0.25 vs. 0.63 mg/L), platelet (222.9 vs. 245.9 K/uL) and PTT (27.6 vs. 29.6 seconds) were also found to be significantly enhanced in CAD patients. Based on the severity of IR [HOMA index up to 3 and ≥ 3], comparison with different parameters such as fibrinogen, D-dimer, C-peptide and insulin in CAD groups were also made. As per HOMA index, fibrinogen level was found to be significantly increased in below and above 3 categories. Moreover, C-peptide (P < 0.01) and insulin (P < 0.001) levels also showed significant association with both HOMA groups. Our study provides an insight towards the association of fibrinogen and IR in CAD patients with respect to severity.

The role of mitochondrial defects and oxidative stress in Alzheimer's disease.

Alzheimer's disease (AD) is a complex, progressive, and irreversible neurodegenerative disorder. Recent reports suggest that it affects more than 36 million people worldwide and accounts 60-80% of all cases of dementia. It is characterised by aberrations of multiple interactive systems and pathways, which ultimately lead to memory loss and cognitive dysfunction. The exact mechanisms and initial triggering factors that underpin the known pathological defects in AD remain to be fully elucidated. In addition, an effective treatment strategy to reduce the progression of AD is yet to be achieved. In the light of above-mentioned facts, our article deals with the exploration of the mitochondrial defect and oxidative stress leading to this devastating disease. In this communication, we have highlighted specific mitochondrial and antioxidant-directed approach to ameliorate and manage AD. Nonetheless, new approaches should also be investigated that could tackle various molecular events involved in AD pathogenicity.

Effect of Diets, Familial History, and Alternative Therapies on Genomic Instability of Breast Cancer Patients.

This study evaluates a correlation between family history, micronutrients intake, and alternative therapies with genetic instability, before and during breast cancer treatment. For this study, a total of 150 women were selected. Among those, 50 women were breast cancer patients on chemotherapy, while 50 breast cancer patients were on radiotherapy, and 50 were healthy females. All the participants signed the informed consent form and answered the public health questionnaire. Samples of buccal epithelial and peripheral blood cells were collected and analyzed through micronucleus and comet assays. The cells were evaluated for apoptosis and DNA damage. Results showed the association of patients' family history with an increase in toxicogenetic damage before and during cancer therapy. On the other hand, patients with late-onset cancer also presented genetic instability before and during therapy, along with those who did not take sufficient vegetables and alternative therapies. A positive correlation was observed between the genetic instability and alternative therapies, while inverse correlation was recorded with the vegetable consumption. Results clearly explain that the nutritional aspects and alternative therapies influence the genetic instability before and during cancer therapies especially in radiotherapy treated patients. Our data could be used for the monitoring therapies and management of breast cancer patients.

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.

Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of ß-amyloid (Aß) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances. Approximately, 60%-80% of all cases of dementia in the world are patients with AD. In view of the continuous rise of this disease especially in the aged population, there is a dire need to come up with a novel compound and/or mixture that could work against this devastating disease. In this regard, the best is to rely on natural compounds rather than synthetic ones, because natural compounds are easily available, cost-effective, and comparatively less toxic. To serve this purpose, lately, scientific community has started exploring the possibility of using different polyphenols either solitary or in combination that can serve as therapeutics against AD. In the current article, we have summarized the role of various polyphenols, namely quercetin, resveratrol, curcumin, gallocatechins, cinnamic acid, caffeine, and caffeic acid as an inhibitor of cholinesterase for the treatment of AD. We have also tried to uncover the mechanistic insight on the action of these polyphenols against AD pathogenicity.