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.

Polyphenols as anticancer agents: Toxicological concern to healthy cells.

Polyphenols are a group of diverse chemical compounds present in a wide range of plants. Various biological properties such as antiallergic, antiviral, antibacterial, anticarcinogenic, antiinflammatory, antithrombotic, vasodilatory, and hepatoprotective effect of different polyphenols have been reported in the scientific literature. The major classes of polyphenols are flavonoids, stilbenoids, lignans, and polyphenolic acids. Flavonoids are a large class of food constituents comprising flavones, isoflavanones, flavanones, flavonols, catechins, and anthocyanins sub-classes. Even with seemingly broad biological activities, their use is minimal clinically. Among the other concurrent problems such as limited bioavailability, rapid metabolism, untargeted delivery, the toxicity associated with these polyphenols has been a topic of concern lately. These polyphenols have been reported to result in different forms of toxicity that include organ toxicity, genotoxicity, mutagenicity, cytotoxicity, etc. In the present article, we have tried to unravel the toxicological aspect of these polyphenols to healthy cells. Further high-quality studies are needed to establish the clinical efficacy and toxicology concern leading to further exploration of these polyphenols.

Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family.

OBJECTIVE: Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly. METHODS: Whole exome sequencing was carried out to find the novel mutation and the results was further validated using Sanger sequencing analysis. This study was done in the Center of excellence in Genomic Medicine and Research, King Abdulaziz University under KACST project during 2017 and 2018. RESULTS: We report a novel compound heterozygous mutations c.797C>T in exon 7 and c.1102G>A in exon 9 of the WD repeat domain 62 (WDR62) (OMIM 604317) gene in two affected siblings in Saudi family with intellectual disability, speech impediments walking difficulty along with primary microcephaly. Two rare, missense variants were detected in heterozygous state in the WDR62 gene in these two affected individuals from the heterozygous parents. CONCLUSIONS: A compound heterozygous mutations c.797C>T in exon 7 and c.1102G> A in exon 9 of the WDR62 gene was identified. WDR62 gene is very important gene and mutation can lead to neuro developmental defects, brain malformations, reduced brain and head size. These results should be taken into consideration during prognostic discussions and mutation spectrum with affected patients and their families in the Saudi population.

Hepato-protective effect of Allium sativum against immobilization stress in rats.

The purpose of the current study was to examine immobilization stress-induced antioxidant defense changes and estimation of the antioxidant potential of pre and post stress treatment of aqueous garlic extract in rat's liver. For this purpose, male Albino Wistar rats were treated with aqueous garlic extract both pre and after 6 h of immobilization stress. Pro-oxidant status of rat liver was evaluated by determining the levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), glucose, uric acid and the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). In response to 6 h of immobilization stress a significant rise in the level of above mentioned liver enzymes were recorded. However, SOD, CAT and GST enzymatic activities showed a sharp decline. The extract treatment before and after stress, almost reverted the activities of studied biochemical parameters towards their control values. Current study highlighted the antioxidant potential of garlic extracts. Based on our study, we recommend the use of garlic extract as nutritional supplement for combating oxidative stress induced damage.

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.

Copy number variations in Saudi family with intellectual disability and epilepsy.

BACKGROUND: Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs) are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging. RESULTS: In order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID), and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127-4337759) and the potential gene in this region is CSMD1 (OMIM: 612279). Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR. CONCLUSIONS: We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing epileptic disorder, may help to improve the clinical management of individual cases in decreasing the burden of epilepsy in Saudi Arabia.

Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

Altered galectin glycosylation: potential factor for the diagnostics and therapeutics of various cardiovascular and neurological disorders.

Galectins are ß-galactoside binding mammalian proteins characterized by the presence of a conserved carbohydrate recognition domain, expressed in almost all taxa of living organisms and involved in broad range of significant biological and physiological functions. Previously, we reported the purification and extensive characterization of galectin-1 from goat (Capra hircus) heart. Interestingly, the purified protein was found to have significant level of glycosylation. This intrigued us to evaluate the involvement of glycosylation in relation to protein's structural and functional integrity in its purified form. In the present study, an extensive comparative physicochemical characterization has been performed between the glycosylated and deglycosylated form of the purified protein. Deglycosylation resulted in an enhanced fluorescence quenching and marked reduction in pH and thermal stability of the purified galectin. Exposure to various biologically active chemicals showed significant differences in the properties and stability profile, causing significant deviations from its regular secondary structure in the deglycosylated form. These results clearly indicated enhanced structural and functional stabilization in the glycosylated galectin. The data revealed herein adds a vital facet demonstrating the significance of galectin expression and glycosylation in causation, progression, and possible therapeutics of associated clinical disorders. Our approach also allowed us to define some key interactions between the purified galectin and carbohydrate ligands that could well serve as an important landmark for designing new drug protocols for various cardiovascular and neurological disorders.

Gene-environment interactions in heavy metal and pesticide carcinogenesis.

Cancer is a complex disease involving a sequence of gene-environment interactions. Lifestyle, genetics, dietary factors, and environmental pollutants can increase the risk of cancer. Gene-environment interactions have been studied by a candidate-gene approach focusing on metabolism, DNA repair, and apoptosis. Here, we review the influence of gene-environment interactions in carcinogenesis, with emphasis on heavy metal and pesticide exposures.

Synthesis and Neurobehavioral Evaluation of a Potent Multitargeted Inhibitor for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) poses a significant health challenge worldwide, affecting millions of individuals, and projected to increase further as the global population ages. Current pharmacological interventions primarily target acetylcholine deficiency and amyloid plaque formation, but offer limited efficacy and are often associated with adverse effects. Given the multifactorial nature of AD, there is a critical need for novel therapeutic approaches that simultaneously target multiple pathological pathways. Targeting key enzymes involved in AD pathophysiology, such as acetylcholinesterase, butyrylcholinesterase, beta-site APP cleaving enzyme 1 (BACE1), and gamma-secretase, is a potential strategy to mitigate disease progression. To this end, our research group has conducted comprehensive in silico screening to identify some lead compounds, including IQ6 (SSZ), capable of simultaneously inhibiting the enzymes mentioned above. Building upon this foundation, we synthesized SSZ, a novel multitargeted ligand/inhibitor to address various pathological mechanisms underlying AD. Chemically, SSZ exhibits pharmacological properties conducive to AD treatment, featuring pyrrolopyridine and N-cyclohexyl groups. Preclinical experimental evaluation of SSZ in AD rat model showed promising results, with notable improvements in behavioral and cognitive parameters. Specifically, SSZ treatment enhanced locomotor activity, ameliorated gait abnormalities, and improved cognitive function compared to untreated AD rats. Furthermore, brain morphological analysis demonstrated the neuroprotective effects of SSZ, attenuating Aß-induced neuronal damage and preserving brain morphology. Combined treatment of SSZ and conventional drugs (DON and MEM) showed synergistic effects, suggesting a potential therapeutic strategy for AD management. Overall, our study highlights the efficacy of multitargeted ligands like SSZ in combating AD by addressing the complex etiology of the disease. Further research is needed to elucidate the full therapeutic potential of SSZ and the exploration of similar compounds in clinical settings, offering hope for an effective AD treatment in the future.

Assessment of groundwater geochemistry for drinking and irrigation suitability in Jaunpur district of Uttar Pradesh using GIS-based statistical inference.

The quality of groundwater in the Jaunpur district of Uttar Pradesh is poorly studied despite the fact that it is the only supply of water for both drinking and irrigation and people use it without any pre-treatment. The evaluation of groundwater quality and suitability for drinking and irrigation is presented in this study. Groundwater samples were collected and analysed by standard neutralisation and atomic emission spectrophotometry for major anions (HCO3-, SO42-, Cl-, F-, NO3-), cations (Ca2+, Mg2+, Na+, K+), and heavy metals (Cd, Mn, Zn, Cu, and Pb). The geographic information system (GIS) and statistical inferences were utilised for the spatial mapping of the groundwater's parameters. The potential water abstraction (i.e. taking water from sources such as rivers, streams, canals, and underground) for irrigation was assessed using the sodium absorption ratio (SAR), permeability index (PI), residual sodium carbonate (RSC), and Na percentage. According to the findings, the majority of the samples had higher EC, TDS, and TH levels, indicating that they should be avoided for drinking and irrigation. The positive correlation coefficient between chemical variability shows that the water chemistry of the studied region is influenced by geochemical and biological causes. According to the USSL (United States Salinity Laboratory) diagram, most of the samples fall under the C2-S1 and C3-S1 moderate to high salt categories. Some groundwater samples were classified as C4-S3 class which is unfit for irrigation and drinking. This study suggests that the groundwater in the study area is unfit for drinking without treatment. However, the majority of the samples were suitable for irrigation.

Synthesis and computational insights of flavone derivatives as potential estrogen receptor alpha (ER-α) antagonist.

Hormone-related breast cancer is mostly caused by interactions with estrogen receptor alpha (ER-α), which functions as a transcription factor to control the transcription of numerous genes. Flavones are considered a good substrate for the estrogen receptor. Substitution of the N-heterocyclic ring on the flavon structure may potentiate its anticancer effect. A series of flavon derivatives with an N-heteroaryl ring at the 4' position of the B ring of flavon were designed, prepared and evaluated for in vitro breast cancer activity. Binding interactions of the PzFL, PzF, PiFL, PiF and IFL compounds with ER-α were studied by molecular docking. Molecular dynamics simulation studies were carried out in order to determine the stability and convergence of protein-ligand complexes. The compounds were produced by cyclizing chalcones and chalcones were produced by Claisen-Schmidt condensation of substituted aldehydes and 2-hydroxy acetophenone. Breast cancer activity was evaluated by the MTT assay on MCF-7 cell lines. Also, compounds were studied for their estrogen receptor binding potential on the same cell lines. Molecular docking of compounds showed a good docking score. The molecular dynamics of these compounds expressed stable root mean square deviation, stable radius of gyration and low binding energy, suggesting that ligand bound to protein is quite stable in the complex. MTT assay on MCF-7 cell lines reported PzF and IFL were the most active compounds with lower IC50 values. ER-α binding assay of these compounds revealed the presence of binding interactions with receptors. This study offers a viable reference point for the design of flavon-incorporated N-heterocyclic ring derivatives as breast cancer compounds.Communicated by Ramaswamy H. Sarma.

Pharmacological Inhibition of Class III Alcohol Dehydrogenase 5: Turning Remote Ischemic Conditioning Effective in a Diabetic Stroke Model.

The restoration of cerebral blood flow (CBF) to achieve brain tissue oxygenation (PbtO2) is the primary treatment for ischemic stroke, a significant cause of adult mortality and disability worldwide. Nitric oxide (NO) and its bioactive s-nitrosylated (SNO) reservoirs, such as s-nitrosoglutathione (GSNO), induce hypoxic vasodilation to enhance CBF during ischemia. The endogenous pool of SNOs/GSNO is enhanced via the activation of endothelial NO synthase (eNOS/NOS3) and by the suppression of class III alcohol dehydrogenase 5 (ADH5), also known as GSNO reductase (GSNOR). Remote ischemic conditioning (RIC), which augments NOS3 activity and SNO, is an emerging therapy in acute stroke. However, RIC has so far shown neutral effects in stroke clinical trials. As the majority of stroke patients are presented with endothelial dysfunctions and comorbidities, we tested the hypothesis that NOS3 dysfunction and diabetes will abolish the protective effects of RIC therapy in stroke, and the prior inhibition of GSNOR will turn RIC protective. Our data demonstrate that RIC during thrombotic stroke failed to enhance the CBF and the benefits of thrombolysis in NOS3 mutant (NOS3+/-) mice, a genetic model of NOS3 dysfunction. Interestingly, thrombotic stroke in diabetic mice enhanced the activity of GSNOR as early as 3 h post-stroke without decreasing the plasma nitrite (NO2-). In thrombotic stroke, neither a pharmacological inhibitor of GSNOR (GRI) nor RIC therapy alone was protective in diabetic mice. However, prior treatment with GRI followed by RIC enhanced the CBF and improved recovery. In a reperfused stroke model, the GRI-RIC combination therapy in diabetic mice augmented PbtO2, a translatory signature of successful microvascular reflow. In addition, RIC therapy unexpectedly increased the inflammatory markers at 6 h post-stroke in diabetic stroke that were downregulated in combination with GRI while improving the outcomes. Thus, we conclude that preexisting NOS3 dysfunctions due to comorbidities may neutralize the benefits of RIC in stroke, which can be turned protective in combination with GRI. Our findings may support the future clinical trial of RIC in comorbid stroke. Further studies are warranted to test and develop SNO reservoirs as the blood-associated biomarker to monitor the response and efficacy of RIC therapy in stroke.

Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage.

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of "clinically" relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, "IV-effects" of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 µg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.

SOD2 deficiency-induced oxidative stress attenuates steroidogenesis in mouse ovarian granulosa cells.

This study investigated the effects of SOD2 (MnSOD)-deficiency-induced excessive oxidative stress on ovarian steroidogenesis in vivo and isolated and cultured granulosa cells using WT and Sod2+/- mice. Basal and 48 h eCG-stimulated plasma progesterone levels were decreased ~50% in female Sod2+/- mice, whereas plasma progesterone levels were decreased ~70% in Sod2+/- mice after sequential stimulation with eCG followed by hCG. Sod2+/- deficiency caused about 50% reduction in SOD2 activity in granulosa cells. SOD2-deficiency also caused a marked reduction in progestins and estradiol in isolated granulosa cells. qRT-PCR measurements indicated that the mRNA expression levels of StAR protein and steroidogenic enzymes are decreased in the ovaries of Sod2+/- mice. Further studies showed a defect in the movement of mobilized cytosolic cholesterol to mitochondria. The ovarian membrane from Sod2+/- mice showed higher susceptibility to lipid peroxidation. These data indicates that SOD2-deficiency induced oxidative stress inhibits ovarian granulosa cell steroidogenesis primarily by interfering with cholesterol transport to mitochondria and attenuating the expression of Star protein gene and key steroidogenic enzyme genes.

Anticancer Potential of Biogenic Silver Nanoparticles: A Mechanistic Study.

The continuous loss of human life due to the paucity of effective drugs against different forms of cancer demands a better/noble therapeutic approach. One possible way could be the use of nanostructures-based treatment methods. In the current piece of work, we have synthesized silver nanoparticles (AgNPs) using plant (Heliotropiumbacciferum) extract using AgNO3 as starting materials. The size, shape, and structure of synthesized AgNPs were confirmed by various spectroscopy and microscopic techniques. The average size of biosynthesized AgNPs was found to be in the range of 15 nm. The anticancer potential of these AgNPs was evaluated by a battery of tests such as MTT, scratch, and comet assays in breast (MCF-7) and colorectal (HCT-116) cancer models. The toxicity of AgNPs towards cancer cells was confirmed by the expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR. The cell viability assay showed an IC50 value of 5.44 and 9.54 µg/mL for AgNPs in MCF-7 and HCT-116 cell lines respectively. We also observed cell migration inhibiting potential of AgNPs in a concentration-dependent manner in MCF-7 cell lines. A tremendous rise (150-250%) in the production of ROS was observed as a result of AgNPs treatment compared with control. Moreover, the RT-PCR results indicated the difference in expression levels of pro/antiapoptotic proteins in both cancer cells. All these results indicate that cell death observed by us is mediated by ROS production, which might have altered the cellular redox status. Collectively, we report the antimetastasis potential of biogenic synthesized AgNPs against breast and colorectal cancers. The biogenic synthesis of AgNPs seems to be a promising anticancer therapy with greater efficacy against the studied cell lines.

An Update on the Association of Protein Kinases with Cardiovascular Diseases.

BACKGROUND: Protein kinases are the enzymes involved in phosphorylation of different proteins which leads to functional changes in those proteins. They belong to serine-threonine kinases family and are classified into the AGC (Protein kinase A/ Protein kinase G/ Protein kinase C) families of protein and Rho-associated kinase protein (ROCK). The AGC family of kinases are involved in G-protein stimuli, muscle contraction, platelet biology and lipid signaling. On the other hand, ROCK regulates actin cytoskeleton which is involved in the development of stress fibres. Inflammation is the main signal in all ROCK-mediated disease. It triggers the cascade of a reaction involving various proinflammatory cytokine molecules. METHODS: Two ROCK isoforms are found in mammals and invertebrates. The first isoforms are present mainly in the kidney, lung, spleen, liver, and testis. The second one is mainly distributed in the brain and heart. RESULTS: ROCK proteins are ubiquitously present in all tissues and are involved in many ailments that include hypertension, stroke, atherosclerosis, pulmonary hypertension, vasospasm, ischemia-reperfusion injury and heart failure. Several ROCK inhibitors have shown positive results in the treatment of various disease including cardiovascular diseases. CONCLUSION: ROCK inhibitors, fasudil and Y27632, have been reported for significant efficiency in dropping vascular smooth muscle cell hyper-contraction, vascular inflammatory cell recruitment, cardiac remodelling and endothelial dysfunction which highlight ROCK role in cardiovascular diseases.

Exploration of Various Proteins for the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. It is the most frequent cause of memory loss and dementia in elderly individuals worldwide. The extracellular deposition of beta amyloid (Aß), intracellular neurofibrillary tangles (NFTs) retention, neuronal decline and neurotransmitter system derangement are the patho-physiological marker of this devastated disease Objective: In view of limited treatment option and their success rate, there is an urgent need to explore the vast array of proteomes for the management of AD. These proteins could be therapeutically targeted to prevent the progression of this disease. In the present review, we tried to uncover several proteins that could be exploited in AD therapeutics. CONCLUSION: Based on our article, we conclude that proteome based AD treatment needs more refinements and approaches to achieve the desired success rate.

Common Therapeutic Modalities Against Diabetes and Associated Cardiovascular Disease.

Despite recent advances in medical research, the incidence of diabetes and cardiovascular disease (CVD)-induced fatal events is increasing. The literature point towards several co-occurring pathways that could lead to terminal complications related with these diseases. Different pathophysiological alterations such as hyperglycaemia, hyperinsulinaemia, insulin resistance, obesity, endothelial dysfunction and oxidative stress lead to the initiation and progression of atherosclerotic plaques. In view of the continuous rise in fatal events and overlapping pathological conditions associated with CVD and diabetes, there is a critical need to develop a common treatments against these diseases. The present review highlights the possible use of common drugs that could target diabetes and associated CVD.

Galectins-A Potential Target for Cardiovascular Therapy.

Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell-cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of ß-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis. In recent times, the role of Gals in the development of cardiovascular disease (CVD) has gained attention. Gals have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with Gals. There is also a role for Gals in the development of myocarditis by their influence on inflammatory processes. Moreover, Gal acts as a biomarker for the severity of myocardial ischemia and heart failure (HF). This review summarizes the association between Gals and the development and pathogenesis of CVD like atherosclerosis, stroke, myocardial infarction, and HF. A comprehensive outline of the association between Gals and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis has also been provided. Modulation of Gal signaling holds great promise for the treatment of CVD as evident from preclinical studies.