EVALUATING ULTRA-WIDEFIELD IMAGING UTILITY IN THE DETECTION OF TREATMENT-REQUIRING PERIPHERAL RETINAL TEARS AND HOLES.

PURPOSE: To determine the utility of ultra-widefield (UWF) imaging in detecting pathologic peripheral retinal tears and holes. METHODS: This was a retrospective, observational study. One-hundred ninety-eight eyes of 198 patients diagnosed with acute posterior vitreous detachment were included. Eyes were divided into two groups: 89 eyes with peripheral retinal holes and tears treated with laser retinopexy (treatment group) and 109 control eyes. Patients underwent UWF imaging and indirect ophthalmoscopy with scleral depression. UWF images from both groups were reviewed by two blinded graders and then compared with funduscopic examination and medical records. RESULTS: UWF imaging identified 60 of the 89 eyes (sensitivity of 67.4%) found to have treatment-requiring peripheral retinal lesions and 107 of the 109 control eyes (specificity of 98.2%).The distribution of misses based on octant location did reach statistical significance ( P = 0.004). Lesions anterior to the equator were more likely to be missed (21/41 eyes, 51.2%) compared with those located posterior to the equator (4/20 eyes, 25.0%) and at the equator (4/28, 14.3%), P = 0.002. The combined discordance rate between graders in the entire cohort was 12.1% (24/198 eyes) yielding an interrater agreement of 87.9%. CONCLUSION: UWF imaging showed a moderate sensitivity and high specificity in detecting treatment-requiring retinal tears and holes, with high interrater agreement. Given there is only a moderate sensitivity in identifying treatment-requiring retinal tears and holes, UWF imaging can assist with clinical examination, but a 360-degree scleral depressed examination should remain the gold standard.

HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.

Voltage-gated proton currents regulate generation of reactive oxygen species (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor (BCR) results in the production of ROS that participate in B cell activation, but the involvement of proton channels is unknown. We report here that the voltage-gated proton channel HVCN1 associated with the BCR complex and was internalized together with the BCR after activation. BCR-induced generation of ROS was lower in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted in less activation of the kinases Syk and Akt, impaired mitochondrial respiration and glycolysis and diminished antibody responses in vivo. Our findings identify unanticipated functions for proton channels in B cells and demonstrate the importance of ROS in BCR signaling and downstream metabolism.

Emerging Roles of Extracellular Vesicles Derived Non-Coding RNAs in the Cardiovascular System.

Cardiovascular disease is the leading cause of morbidity and mortality all over the world. Emerging evidence emphasize the importance of extracellular vesicles (EVs) in the cell to cell communication in the cardiovascular system which is majorly mediated through non-coding RNA cargo. Advancement in sequencing technologies revealed a major proportion of human genome is composed of non-coding RNAs viz., miRNAs, lncRNAs, tRNAs, snoRNAs, piRNAs and rRNAs. However, our understanding of the role of ncRNAs-containing EVs in cardiovascular health and disease is still in its infancy. This book chapter provides a comprehensive update on our understanding on the role of EVs derived ncRNAs in the cardiovascular pathophysiology and their therapeutic potential.

KLF7 promotes preadipocyte proliferation via activation of the Akt signaling pathway by Cis-regulating CDKN3.

Krüppel-like transcription factor 7 (KLF7) promotes preadipocyte proliferation; however, its target gene in this process has not yet been identified. Using KLF7 ChIP-seq analysis, we previously showed that a KLF7-binding peak is present upstream of the cyclin-dependent kinase inhibitor 3 gene ( CDKN3) in chicken preadipocytes. In the present study, we identify CDKN3 as a target gene of KLF7 that mediates the effects of KLF7 on preadipocyte proliferation. Furthermore, 5'-truncating mutation analysis shows that the minimal promoter is located between nt -160 and nt -7 (relative to the translation initiation codon ATG) of CDKN3. KLF7 overexpression increases CDKN3 promoter activity in the DF-1 and immortalized chicken preadipocyte (ICP1) cell lines. Deletion of the putative binding site of KLF7 abolishes the promotive effect of KLF7 overexpression on CDKN3 promoter activity. Moreover, CDKN3 knockdown and overexpression assays reveal that CDKN3 enhances ICP1 cell proliferation. Flow cytometry analysis shows that CDKN3 accelerates the G1/S transition. Furthermore, we find that KLF7 promotes ICP1 cell proliferation via Akt phosphorylation by regulating CDKN3. Taken together, our results suggest that KLF7 promotes preadipocyte proliferation by activating the Akt signaling pathway by cis-regulating CDKN3, thus driving the G1/S transition.

Ellagic acid protects type II collagen induced arthritis in rat via diminution of IKB phosphorylation and suppression IKB-NF-kB complex activation: in vivo and in silico study.

OBJECTIVE: The present study was designed to explore the potential anti-inflammatory and anti-arthritic effects of ellagic acid (EA) in collagen-induced arthritis (CIA). METHODS: CIA rats were treated with MTX (0.25 mg/kg body wt.) and EA (50 mg/kg b.wt.) for a period of 20 days. The effects of treatment in the rats were assessed biochemically by analyzing inflammatory mediators (NF-kB, iNOS, TNF-α, IL-1ß, IL-6 and IL-10) and oxidative stress related parameters (MPO, NO, LPO, catalase, SOD, GSH). In addition, we also assessed the expression of some inflammatory mediators TNF-α, CD8 + though immunohistochemistry in the joint tissue. RESULTS: In the present study, we found expression and synthesis of transcription factor NF-kB was prominent in CIA rats. In addition, main pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and the anti-inflammatory IL-10, was also stand out. Further, reactive oxygen/nitrogen species was also elevated in CIA rats. Treatment with EA ameliorates all the above mentioned inflammatory and oxidative stress related parameters to near normal. Further, we also confirmed the expression of TNF-α, CD8+ T cells through immunohistochemistry was mitigates in joint tissue of EA treated rats. We find EA significantly inhibited the developmental phase of arthritis. CONCLUSION: These results suggest that EA act as potent anti-arthritic and anti-inflammatory agent that could be used as a tool for the development of new drug for the treatment of arthritis.

Association of optical cataract indices with cataract severity and visual function.

PURPOSE: The purpose of this study is to determine the correlation between subjective and optical measurements used during cataract evaluation, including the iTrace Dysfunctional Lens Index (DLI), the HD Analyzer Objective Scatter Index (OSI), Lens Opacities Classification System III (LOCS III), Visual Function-14 Questionnaire (VF-14), and the Pelli-Robson Contrast Sensitivity Chart (PRCSC). METHODS: Seventy eyes from 70 patients were enrolled, including all stages of age-related nuclear cataracts. The LOCS III-NO with a cutoff of 3.2 was chosen to divide the population into two groups. Eyes with corneal or retinal pathology were excluded. All patients were evaluated with the iTrace's DLI, HD Analyzer's OSI, LOCS III, VF-14, and the PRCSC during each follow-up visit. Correlation analyses were performed using Stata software, version 14.0, StataCorp. RESULTS: The LOCS III-NO, DLI, OSI, and VF-14 questionnaire each correlated moderately with the BCVA with a Spearman rho value of 0.37, - 0.45, 0.40, and - 0.35, respectively. The DLI correlated moderately with LOCS III-NO with a rho value of - 0.37 and with the VF-14 questionnaire with a rho value of 0.35. The OSI correlated with both the contrast sensitivity and DLI with a rho value of - 0.35 and - 0.55, respectively. CONCLUSIONS: The DLI correlated with cataract symptoms (measured by the VF-14 questionnaire) in addition to BCVA. The OSI correlated moderately with contrast sensitivity and BCVA. The highest correlation was between DLI and OSI.

Proteosomal degradation impairs transcytosis of AAV vectors from suprachoroidal space to retina.

Suprachoroidal injection provides a new route of delivery for AAV vectors to retinal pigmented epithelial cells and photoreceptors that can be done in an outpatient setting and is less invasive and potentially safer than subretinal injection, the most common route of delivery for ocular gene therapy. After suprachoroidal injection of AAV8 or AAV9 vectors, there is strong transduction of photoreceptors, but it is unclear how vector traverses the retinal pigmented epithelium. In this study, we found that transduction of photoreceptors was significantly increased after suprachoroidal injection of AAV2tYF-CBA-GFP versus AAV2-CBA-GFP vector. Compared with AAV2, AAV2tYF is more resistant to proteosomal degradation. Treatment with protease inhibitors significantly increased photoreceptor transduction after suprachoroidal injection of AAV5-GRK1-GFP. These data suggest that after suprachoroidal injection, AAV vectors access photoreceptors by transcytosis through retinal pigmented epithelial cells during which they are subject to proteosomal degradation, which if suppressed can enhance transduction of photoreceptors.

Lymphotoxin-ß receptor signaling through NF-κB2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells.

Lymph node development during embryogenesis involves lymphotoxin-ß receptor engagement and subsequent differentiation of a poorly defined population of mesenchymal cells into lymphoid tissue organizer cells. Here, we showed that embryonic mesenchymal cells with characteristics of adipocyte precursors present in the microenvironment of lymph nodes gave rise to lymph node organizer cells. Signaling through the lymphotoxin-ß receptor controlled the fate of adipocyte precursor cells by blocking adipogenesis and instead promoting lymphoid tissue stromal cell differentiation. This effect involved activation of the NF-κB2-RelB signaling pathway and inhibition of the expression of the key adipogenic factors Pparγ and Cebpα. In vivo organogenesis assays show that embryonic and adult adipocyte precursor cells can migrate into newborn lymph nodes and differentiate into a variety of lymph node stromal cells. Thus, we propose that adipose tissues act as a source of lymphoid stroma for lymph nodes and other lymphoid structures associated with fat.

Drug-induced maculopathy.

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of drug-induced maculopathies including their clinical presentations, diagnostic findings, and treatment options. With the increasing pace of development and arrival of drugs to the market, this review aims to inform retina specialists of relevant side effects that may be encountered in a clinical practice setting. RECENT FINDINGS: The major themes visited in this article focus on relevant findings of drugs that cause pigmentary and crystalline maculopathy, photoreceptor dysfunction, cystoid macular edema, central serous choroidopathy, uveitis, and vascular damage. SUMMARY: The current review reports updated findings and discusses the pathophysiologic mechanisms, presentations, and treatments of drug-induced maculopathies.

Mouse embryonic stem cell-derived cardiomyocytes cease to beat following exposure to monochromatic light: association with increased ROS and loss of calcium transients.

We earlier established the mouse embryonic stem (ES) cell "GS-2" line expressing enhanced green fluorescent protein (EGFP) and have been routinely using it to understand the molecular regulation of differentiation into cardiomyocytes. During such studies, we made a serendipitous discovery that functional cardiomyocytes derived from ES cells stopped beating when exposed to blue light. We observed a gradual cessation of contractility within a few minutes, regardless of wavelength (nm) ranges tested: blue (~420-495), green (~510-575), and red (~600-700), with green light manifesting the strongest impact. Following shifting of cultures back into the incubator (darkness), cardiac clusters regained beatings within a few hours. The observed light-induced contractility-inhibition effect was intrinsic to cardiomyocytes and not due to interference from other cell types. Also, this was not influenced by any physicochemical parameters or intracellular EGFP expression. Interestingly, the light-induced cardiomyocyte contractility inhibition was accompanied by increased intracellular reactive oxygen species (ROS), which could be abolished in the presence of N-acetylcysteine (ROS quencher). Besides, the increased intracardiomyocyte ROS levels were incidental to the inhibition of calcium transients and suppression of mitochondrial activity, both being essential for sarcomere function. To the best of our knowledge, ours is the first report to demonstrate the monochromatic light-mediated inhibition of contractions of cardiomyocytes with no apparent loss of cell viability and contractility. Our findings have implications in cardiac cell biology context in terms of 1) mechanistic insights into light impact on cardiomyocyte contraction, 2) potential use in laser beam-guided (cardiac) microsurgery, photo-optics-dependent medical diagnostics, 3) transient cessation of hearts during coronary artery bypass grafting, and 4) functional preservation of hearts for transplantation.

Metipranolol promotes structure and function of retinal photoreceptors in the rd10 mouse model of human retinitis pigmentosa.

Metipranolol is a ß-adrenergic receptor antagonist that is given orally for the treatment of hypertension and also applied topically to the cornea for treating glaucoma. It also inhibits nitrosative stress which has previously been shown to be the cause of cone photoreceptor death in retinitis pigmentosa. In this study, we tested the hypothesis that metipranolol protects photoreceptor structure and function in the mouse model rd10. At P35, compared with vehicle-treated rd10 mice in which rod degeneration was nearly complete, rd10 mice given daily subcutaneous injections of 40 mg/kg of metipranolol had reduction in markers of nitrosative stress, fewer TUNEL-positive cells, increased outer nuclear layer thickness, and substantially more staining for rhodopsin. This was accompanied by significantly higher mean scotopic and photopic electroretinogram b-wave amplitudes indicating improved photoreceptor function. At P50, metipranolol-treated rd10 mice had decreased 3-nitrotyrosine staining in the retina, increased immunostaining for cone arrestin, a marker for cone photoreceptors, and significantly higher scotopic and photopic b-wave amplitudes at the highest stimulus intensity compared with vehicle-treated mice. At P65, cone density was significantly higher in metipranolol-treated versus vehicle-injected rd10 mice. Metipranolol applied as eye drops promoted cone photoreceptor function in retinas of rd10 mice greater than subcutaneously injected metipranolol. The reduced nitrosative damage and rescue of functional loss of photoreceptors in rd10 mice suggests that metipranolol, a drug with established ocular safety and tolerability, may have potential for treating patients with retinitis pigmentosa.

Comparative hepatoprotective effect of Nigella sativa pre- and post-treatment to rabbits.

Synthetic drugs are associated with adverse side-effects and rapid increase in resistance to most of them inspires to evaluate plants for their therapeutic values. We have been aimed to suggest the medicinal use of Nigella sativa seed aqueous extract to minimize the severity of liver damage via its antioxidant properties and its role in maintenance of cell ion-homeostasis. Annoyances in serum levels of some antioxidants and trace metals in human hepatitis C infected patients were compared with that from acetaminophen-induced hepatotoxic rabbits. Serum analysis of human patients and that of hepatotoxic rabbits have exhibited the same trend of incidence of liver marker enzymes, antioxidant levels, and trace metal concentrations, except for the serum levels of cobalt. Significance of pre-/ or post-treatment of Nigella sativa to acetaminophen induced-hepatotoxic rabbit has also evaluated. NS post-treatment to rabbits has been found effective in normalizing the levels (P<0.001) of serum liver markers; especially the ALP levels, and the antioxidants; with significant effect on the serum catalase levels. However, NS pre-treatment has shown its role (P<0.001) in maintaining the serum nickel and cobalt concentrations. Therefore, we suggest the use of Nigella sativa seeds as pre-/ or post-treatment therapy, and also as supplement to the normal medications of liver infection to normalize the status of cell antioxidants and trace metal concentrations.

Social Media and Ophthalmology: Perspectives of Patients and Ophthalmologists.

Recent research has analyzed how patients use social media, but little information exists evaluating how patients utilize social media in the perioperative period or how ophthalmologists and eye institutions integrate social media into their practices. This observational study aimed to examine (1) how patients interact on social media when undergoing LASIK and (2) how ophthalmologists and (3) eye institutions utilize social media accounts. We analyzed 2592 Instagram posts between August 2016 and April 2017 on a related hashtag (#lasiksurgery). Content was coded based on time frame of the post in relation to the procedure, references to return to work/activity, post-surgical photographs, mention of the surgical institution, tone, and complaints regarding the procedure. Twitter and Instagram accounts for 30 ophthalmologists and eye institutes were also located. The 20 most recent posts were categorized by message type and topic (physicians, patients, education, conference, etc.). Patients using the hashtag posted photographs (92%), had a positive tone (88%), referenced the clinic where they were treated (62%), and posted during the day of the procedure (44%). Ophthalmologists' personal tweets focused on research conferences (35%), personal topics (25%), and the accomplishments of other physicians (21%). Eye institutions generally posted content relating to institutional promotion (22%), physician accomplishments (20%), and research publications (19%). Similar to other medical specialties, ophthalmology has a meaningful presence on both Twitter and Instagram. While LASIK patients tend to comment on their renewed vision and return to activity, ophthalmologists post to promote their research and accomplishments.

Potential of Nigella sativa seed aqueous extract in ameliorating quinine-induced thrombocytopenia in rats.

Dengue infection is rapidly spreading in most of the countries of south Asia. It is of utmost importance to explore the plants with "anti-thrombocytopenic activity" the dreadful response of dengue fever. The present study was conducted to investigate the potential of aqueous extract of Nigella sativa (black cumin) seeds in alleviating the severity of dengue disease by raising the platelet count (PLT). Serum samples of thirty patients with dengue hemorrhagic fever (DHF) were analysed for different biochemical parameters. When compared with control groups, the patients were found with very low PLT count (7.62 fold), reduced antioxidant levels; catalase (1.4 fold), ascorbic acid (1.1 fold), bilirubin (1.06 fold), and severe deficiency of micronutrient concentrations; cobalt (2.27 fold), iron (2.35 fold) and nickel (71.46 fold). Similar parameters were studied in albino rats to observe the changes in serum levels of biochemical markers, after administration of single dose of choloroquine phosphate (IM, 1.5 mL saline). The drug successfully induced thrombocytopenia along with significant decrease in levels of antioxidants and trace metals. Administration of N. sativa aqueous seed extract (15.25 mg/kg/bw) for 12 days resulted in an increase in PLT count (1.59 fold) as compared to control group. N. sativa post-treatment was found effective in elevating the serum levels of catalase, ascorbic acid, and bilirubin (1.06, 1.58 and 0.4 folds respectively). However, the N. sativa pre-treatment was useful in increasing the levels of micronutrients; iron, nickel and cobalt when compared to quinine-induced group. From the above findings it was suggested that N. sativa seed aqueous extract supplementation would be a promising solution for declined PLT count and associated consequences.

Performance Optimization of Priority Assisted CSMA/CA Mechanism of 802.15.6 under Saturation Regime.

Due to the recent development in the field of Wireless Sensor Networks (WSNs), the Wireless Body Area Networks (WBANs) have become a major area of interest for the developers and researchers. Human body exhibits postural mobility due to which distance variation occurs and the status of connections amongst sensors change time to time. One of the major requirements of WBAN is to prolong the network lifetime without compromising on other performance measures, i.e., delay, throughput and bandwidth efficiency. Node prioritization is one of the possible solutions to obtain optimum performance in WBAN. IEEE 802.15.6 CSMA/CA standard splits the nodes with different user priorities based on Contention Window (CW) size. Smaller CW size is assigned to higher priority nodes. This standard helps to reduce delay, however, it is not energy efficient. In this paper, we propose a hybrid node prioritization scheme based on IEEE 802.15.6 CSMA/CA to reduce energy consumption and maximize network lifetime. In this scheme, optimum performance is achieved by node prioritization based on CW size as well as power in respective user priority. Our proposed scheme reduces the average back off time for channel access due to CW based prioritization. Additionally, power based prioritization for a respective user priority helps to minimize required number of retransmissions. Furthermore, we also compare our scheme with IEEE 802.15.6 CSMA/CA standard (CW assisted node prioritization) and power assisted node prioritization under postural mobility in WBAN. Mathematical expressions are derived to determine the accurate analytical model for throughput, delay, bandwidth efficiency, energy consumption and life time for each node prioritization scheme. With the intention of analytical model validation, we have performed the simulations in OMNET++/MIXIM framework. Analytical and simulation results show that our proposed hybrid node prioritization scheme outperforms other node prioritization schemes in terms of average network delay, average throughput, average bandwidth efficiency and network lifetime.

MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart.

: Cardiovascular disease is the number 1 cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure. Cell therapy (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA (miRNA) in the cardiac muscle and is downregulated in patients with MI. We hypothesized that reprogramming MSCs using miRNA mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs, and the levels of miR-133a were measured by quantitative real-time polymerase chain reaction. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic hearts. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels, and apoptosis-related genes (Apaf-1, Caspase-9, and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function, and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, quantitative real-time polymerase chain reaction data demonstrated a significant decrease in expression of the proapoptotic genes; Apaf-1, caspase-9, and caspase-3 in the miR-133a mimic transplanted group. Furthermore, luciferase reporter assay confirmed that miR-133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of patients undergoing stem cell transplantation for MI.

CenC, a multidomain thermostable GH9 processive endoglucanase from Clostridium thermocellum: cloning, characterization and saccharification studies.

The growing demands of bioenergy has led to the emphasis on novel cellulases to improve efficiency of biodegradation process of plant biomass. Therefore, a thermostable cellulolytic gene (CenC) with 3675 bp was cloned from Clostridium thermocellum and over-expressed in Escherichia coli strain BL21 CodonPlus. It was attested that CenC belongs to glycoside hydrolase family 9 (GH9) with four binding domains, a processive endoglucanase. CenC was purified to homogeneity, producing a single band on SDS-PAGE corresponding to 137.11 kDa, by purification steps of heat treatment combined with ion-exchange chromatography. Purified enzyme displayed optimal activity at pH 6.0 and 70 °C. CenC had a half-life of 24 min at 74 °C, was stable up to 2 h at 60 °C and over a pH range of 5.5-7.5. Enzyme showed high affinity towards various substrates and processively released cellobiose from cellulosic substrates. It efficiently hydrolyzed carboxymethyl cellulose (30 U/mg), ß-Glucan Barley (94 U/mg); also showed activity towards p-nitrophenyl-ß-D-cellobioside (18 U/mg), birchwood xylan (19 U/mg), beechwood xylan (17.5 U/mg), avicel (9 U/mg), whatman filter paper (11 U/mg) and laminarin (3.3 U/mg). CenC exhibited Km, Vmax, Kcat, Vmax Km(-1) and Kcat Km(-1) of 7.14 mM, 52.4 µmol mg(-1) min(-1), 632.85 s(-1), 7.34 min(-1) and 88.63, respectively used CMC as substrate. Recombinant CenC saccharified pretreated wheat straw and bagasse to 5.12 and 7.31%, respectively at pH 7.0 and 45 °C after 2 h incubation. Its thermostability, high catalytic efficiency and independence of inhibitors make CenC enzyme an appropriate candidate for industrial applications and cost-effective saccharification process.

Stem cell transplantation as a therapy for cardiac fibrosis.

Cardiac fibrosis is a fundamental constituent of most cardiac pathologies and represents the upshot of nearly all types of cardiac injury. Generally, fibrosis is a scarring process, characterized by accumulation of fibroblasts and deposition of increasing amounts of extracellular matrix (ECM) proteins in the myocardium. Therapeutic approaches that control fibroblast activity and evade maladaptive processes could represent a potential strategy to attenuate progression towards heart failure. Currently, cell therapy is actively perceived as an alternative to traditional pharmacological management of myocardial infarction (MI). The majority of the studies applying stem cell therapy following MI have demonstrated a decline in fibrosis. However, it was not clearly recognized whether the decline in cardiac fibrosis was due to replacement of dead cardiomyocytes or because of the direct effects of paracrine factors released from the transplanted stem cells on the ECM. Therefore, the main focus of this review is to discuss the impact of different types of stem cells on cardiac fibrosis and associated cardiac remodelling in a variety of experimental models of heart failure, particularly MI.

Emerging role of oxidative stress in metabolic syndrome and cardiovascular diseases: important role of Rac/NADPH oxidase.

'Oxidative stress' is a term defining states of elevated reactive oxygen species (ROS) levels. Normally, ROS control several physiological processes, such as host defence, biosynthesis of hormones, fertilization and cellular signalling. However, oxidative stress has been involved in different pathologies, including metabolic syndrome and numerous cardiovascular diseases. A major source of ROS involved in both metabolic syndrome and cardiovascular pathophysiology is the NADPH oxidase (NOX) family of enzymes. NOX is a multi-component enzyme complex that consists of membrane-bound cytochrome b-558, which is a heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox and p67phox, and the small GTP-binding protein Rac1. Rac1 plays many important biological functions in cells, but perhaps the most unique function of Rac1 is its ability to bind and activate the NOX complex. Furthermore, Rac1 has been reported to be a key regulator of oxidative stress through its co-regulatory effects on both nitric oxide (NO) synthase and NOX. Therefore, the main goal of this review is to give a brief outline about the important role of the Rac1-NOX axis in the pathophysiology of both metabolic syndrome and cardiovascular disease.