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Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative stress. SG-1002 also decreased the expression of hypertrophic/HF protein markers such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), galectin-3, TIMP1, collagen type III, and TGF-β1 in stressed HL-1 cells. Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated without or with H2O2. Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing H2S levels or H2S producing enzymes, CBS, and antioxidant proteins. [ABSTRACT FROM AUTHOR]

Alcorn, Joseph L., Kazi N. Islam, Pampee P. Young, and Carole R. Mendelson. Glucocorticoid inhibition of SP-A gene expression in lung type II cells is mediated via the TTF-1-binding element. Am J Physiol Lung Cell Mol Physiol 286: L767-L776, 2004. First published November 21, 2003; 10.1152/ajplung.00280.2003.-Induction of surfactant protein-A (SP-A) gene expression in fetal lung type II cells by cAMP and IL-1 is mediated by increased binding of thyroid transcription factor-1 (TTF-1) and NF-[kappa]B proteins p50 and p65 to the TTF-1-binding element (TBE) at--183 bp. In type II cell transfections, dexamethasone (Dex) markedly inhibits cAMP-induced expression of rabbit SP-A:human growth hormone (hGH) fusion genes containing as little as ~300 bp of the SP-A 5'-flanking sequence. Dex inhibifion is blocked by RU-486, suggesting a role of the glucocorticoid receptor (GR). The present study was undertaken to define the mechanisms for GR inhibition of SP-A expression. Cotransfection of primary cultures of type II cells with a GR expression vector abrogated cAMP induction of SP-A promoter activity while, at the same time, causing a 60-fold induction of cotransfected mouse mammary, tumor virus (MMTV) promoter. In lung cells transfected with a fusion gene containing three TBEs fused to the basal SP-A promoter, Dex prevented the stimulatory effect of IL-1 on TTF-1 inducfion of SP-A promoter activity, suggesting that the GR inhibits SP-A promoter activity through the TBE. In gel shift assays using nuclear extracts from human fetal type II cells cultured in the absence or presence of cAMP, Dex markedly reduced binding of nuclear proteins to the TBE and blocked the stimulatory effect of cAMP on TBE-binding activity. Our finding that Dex increased expression of the NF-[kappa]B inhibitory partner I[kappa]B-[alpha] suggests that the decrease in TBE-binding activity may be caused, in part, by GR inhibition of NF-[kappa]B interaction with this site. surfactant protein A; fetal lung; glucocorticoid receptor; cAMP; thyroid transcription factor-1

The article focuses on a study which examines the effectiveness of peroxisome proliferator activated receptor gamma (PPARy) agonist rosiglitazone (RSG) in protecting the apoptosis of rat cardiomyocytes (CMC). It mentions several techniques including statistical analysis, western blot analysis and polymerase chain reaction which are used as research methodologies. The result reveals that RSG increased the expression of TRx messenger RNA resulting in the protection of CMCs.

Human immunodeficiency virus (HIV) attacks the immune system and weakens the ability to fight infections/disease. Furthermore, HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. The pathological mechanisms responsible for the increased incidence of cardiovascular disease in HIV patients are largely unknown. We hypothesized that increased oxidative stress and attenuated circulating levels of the cardioprotective gaseous signaling molecules, nitric oxide (NO), and hydrogen sulfide (H2S) were involved in the cardiovascular pathobiology observed in HIV patients. Plasma samples from both HIV patients and age–matched normal subjects were used for all assays. Oxidative stress was determined by analyzing the levels of advanced oxidation protein products (AOPP) and H2O2. Antioxidant levels were determined by measuring the levels of trolox equivalent capacity. ADMA, hs-CRP, and IL-6 were determined by using ELISA. The levels of H2S (free H2S and sulfane sulfur) and NO2 (nitrite) were determined in the plasma samples by using gas chromatography and HPLC, respectively. In the present study we observed a marked induction in the levels of oxidative stress and decreased antioxidant status in the plasma of HIV patients as compared with the controls. Circulating levels of the cardiovascular disease biomarkers: ADMA, hs-CRP (high-sensitivity C-reactive protein), and IL-6 were significantly increased in the circulatory system of HIV patients. The levels of both nitrite and H2S/sulfane sulfur were significantly reduced in the plasma of HIV patients as compared with normal subjects. Our data demonstrate significant increases in circulating biomarkers of oxidative stress and cardiovascular (CV) in conjunction with decreased bioavailability of H2S and NO in HIV patients. Diminished levels of these two cardioprotective gaseous signaling molecules may be involved in the pathogenesis of CV disease in the setting of HIV. [ABSTRACT FROM AUTHOR]

Introduction: Consensus has formed that hydrogen sulfide (H2S) has robust cytoprotective actions in multiple organ systems. The pro-survival actions and biological profiles of H2S are remarkably similar to those of nitric oxide (NO). Although there is recent evidence of cross-talk between H2S and NO, these molecules are thought to modulate independent signaling pathways. Methods/Results: Mice devoid of the key H2S producing enzyme, cystathionine gamma-lyase (CSE KO), exhibited impaired endothelial nitric oxide synthase (eNOS) function and diminished circulating nitrite (0.41 uM vs 0.73μM, p <0.05) nitrosylated protein (3.37nM vs 15.03nM, p <0.05), and cyclic GMP (9.3 vs 28.05pmol/ml, p <0.01) levels compared to wild-type (WT) mice. Further studies revealed that H2S therapy in CSE KO mice restored eNOS function and NO levels. eNOS KO mice and mice with phospho-dead eNOS (S1179A) were subjected to 45min of ischemia, followed by 24h of reperfusion. The H2S donor, Na2S (100μg/kg), or vehicle (0.9% NaCl) was administered 5min before reperfusion. There was no significant change in myocardial infarction in the H2S-treated group compared to the vehicle-treated group. Conclusion: These findings reveal that H2S modulates eNOS activity and nitric oxide signaling. Moreover, the inability of H2S therapy to protect eNOS dysfunctional mice against myocardial ischemia/reperfusion injury indicates that the cardioprotective actions of H2S are dependent on eNOS function and NO signaling. [Copyright &y& Elsevier]

Anesthesia is an essential component of dermatologic procedures, influencing pain management and patient outcomes, including wound healing, infection control, and cosmetic appearance. This review examines the impact of various anesthetic techniques, topical, local, regional, and general, on dermatological outcomes. The findings reveal that while local anesthesia is preferred due to its efficacy and safety, specialized considerations are necessary for pediatric, geriatric, and high-risk patients. Anesthesia-related complications, such as allergic reactions, systemic toxicity, and delayed healing, require careful selection of agents and techniques. Innovations in anesthetic technology, including nanotechnology, microneedle patches, and cryoanesthesia, promise to improve pain management and minimize complications. Personalized anesthesia approaches, informed by genetic and proteomic analyses, offer the potential to optimize individual patient care. However, further research is needed to understand the long-term effects of anesthetic agents on wound healing and scarring, especially in patients with comorbidities. Overall, this review emphasizes the evolving role of anesthesia in dermatology and highlights the need for ongoing innovation to enhance patient care, minimize risks, and improve procedural outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Islam et al.)

Cardiovascular diseases represent the largest worldwide cause of morbidity and mortality. Common signs and symptoms of cardiovascular disease are well characterized and taught in medical curricula, allowing clinicians to quickly recognize and diagnose the more acute and emergent cardiovascular diseases. Dermatological features associated with cardiovascular diseases are less understood but very valuable to appreciate in clinical practice. The present investigation evaluates heart conditions such as heart failure, atherosclerosis, infective endocarditis, and Takotsubo cardiomyopathy, highlighting dermatologic signs that indicate underlying cardiovascular pathology and serve as important diagnostic and prognostic markers., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kaye et al.)

Obesity is a major global issue linked to cardiovascular diseases (CVDs). While lifestyle changes are the primary treatment, medications are often required for long-term weight management and reducing risk in patients with obesity. The cardiovascular effects of many obesity medications are still being studied. This review examines the cardiovascular impact of commonly prescribed obesity medications, focusing on their mechanisms, effectiveness, and safety. A review of the literature was conducted to evaluate the cardiovascular effects of these drugs, including their impact on major cardiovascular outcomes, cholesterol, blood pressure, and other heart-related factors. Some medications, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), show cardiovascular benefits, while others like orlistat have a lesser effect. Medications such as naltrexone-bupropion and phentermine-topiramate offer weight loss but still require further review for their cardiovascular safety. Data on setmelanotide's long-term effects are limited. Obesity medications differ in their effects on cardiovascular health, with some offering more consistent benefits. More studies are needed to fully understand their long-term risks and benefits, but combining medication with lifestyle changes remains key to improving both weight and heart health., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Islam et al.)

Mohs micrographic surgery (MMS) is a precise and effective technique for treating skin cancers, necessitating high accuracy and real-time decision-making to ensure complete tumor removal while preserving healthy tissue. The introduction of the Apple Vision Pro (AVP), an advanced mixed-reality headset, presents a potential technological advancement in surgical practice. The present investigation explores the integration of AVP into Mohs surgery, focusing on its potential to enhance preoperative planning, intraoperative guidance, and postoperative analysis. The AVP's high-resolution displays, advanced eye-tracking technology, and real-time data overlay capabilities may assist in meticulous surgical planning and execution. In the preoperative phase, AVP enables the creation and manipulation of detailed 3D models, providing comprehensive visualizations of tumor margins and critical structures. During surgery, AVP's real-time data overlay aids in precise tumor excision and spatial orientation, reducing errors and improving outcomes. Postoperatively, the AVP facilitates detailed procedural reviews and serves as a robust educational tool for surgical trainees. Despite its promising applications, challenges such as real-time resolution limitations, potential eye strain from prolonged use, and high costs must be addressed for widespread clinical adoption. This review highlights the transformative potential of AVP in Mohs surgery and underscores the need for further research to optimize integration and maximize benefits in dermatological procedures., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kaye et al.)

Cardiovascular disease (CVD) stands as one of the leading causes of morbidity and mortality worldwide, and the continued search for novel therapeutics is vital for addressing this global health challenge. Over the past decade, hydrogen sulfide (H₂S) has garnered significant attention in the field of medical research, as it has been proven to be a cardioprotective gaseous signaling molecule. It joins nitric oxide and carbon monoxide as endogenously produced gasotransmitters. As for its mechanism, H₂S functions through the posttranslational addition of a sulfur group to cysteine residues on target proteins in a process called sulfhydration. As a result, the observed physiological effects of H₂S can include vasodilation, anti-apoptosis, anti-inflammation, antioxidant effects, and regulation of ion channels. Various studies have observed the cardioprotective benefits of H₂S in diseases such as myocardial infarction, ischemia-reperfusion injury, cardiac remodeling, heart failure, arrhythmia, and atherosclerosis. In this review, we discuss the mechanisms and therapeutic potential of H₂S in various CVDs., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Islam et al.)

Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1-III) containing endonuclease III in myocardial ischemia-reperfusion injury and transverse aortic constriction (TAC)-induced heart failure. Male C57/BL6J mice (10-12 wk) were subjected to 45 min of myocardial ischemia and either 24 h or 4 wk of reperfusion. Exscien1-III (4 mg/kg ip) or vehicle was administered at the time of reperfusion. Male C57/BL6J mice were subjected to TAC, and Exscien1-III (4 mg/kg i.p) or vehicle was administered daily starting at 3 wk post-TAC and continued for 12 wk. Echocardiography was performed to assess left ventricular (LV) structure and function. Exscien1-III reduced myocardial infarct size ( P < 0.01) at 24 h of reperfusion and preserved LV ejection fraction at 4 wk postmyocardial ischemia. Exscien1-III attenuated TAC-induced LV dilation and dysfunction at 6-12 wk post-TAC ( P < 0.05). Exscien1-III reduced ( P < 0.05) cardiac hypertrophy and maladaptive remodeling after TAC. Assessment of cardiac mitochondria showed that Exscien1-III localized to mitochondria and increased mitochondrial antioxidant and reduced apoptotic markers. In conclusion, our results indicate that administration of Exscien1-III provides significant protection against myocardial ischemia and preserves myocardial structure and LV performance in the setting of heart failure. NEW & NOTEWORTHY Oxidative stress-induced mitochondrial DNA damage is a prominent feature in the pathogenesis of cardiovascular diseases. In the present study, we demonstrate the efficacy of a novel, mitochondria-targeted fusion protein that traffics endonuclease III specifically for mitochondrial DNA repair in two well-characterized murine models of cardiac injury and failure.

Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.

Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine (n = 18) by unilateral external iliac artery deployment of a full cross-sectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post-CLI day 14, pigs were randomized to placebo (n = 9) or SR-nitrite (80 mg, n = 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease.