Inflammatory bowel disease and the associated risk of dry eye and ocular surface injury: a nationwide matched cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with lacrimal gland dysfunction and ocular inflammation. The objective of this research was to elucidate the temporal relationships between IBD, dry eye disease (DED), and corneal surface damage. METHODS: In a matched nationwide cohort study, we evaluated the risk of DED and corneal surface damage associated with IBD. Multivariable Cox proportional hazards regression analyses were implemented to estimate the risk of ocular complications. RESULTS: A total of 54,293 matched pairs were included for analyses. The median follow-up time was 8.3 years (interquartile range: 5.5 - 10.5). The period incidence of DED was 8.18 and 5.42 per 1000 person-years in the IBD and non-IBD groups, respectively. After adjusting for confounders, statistically significant associations were found between IBD and DED [adjusted hazard ratio (aHR): 1.43, 95% confidence interval (CI): 1.35 - 1.51, p < 0.0001], Sjögren's syndrome-related (aHR: 1.67, 95% CI:1.46 - 1.90, p < 0.0001) and non-Sjögren's syndrome-related subtypes (aHR: 1.38, 95% CI: 1.30 - 1.46, p < 0.0001). Furthermore, increased risks of corneal surface damage (aHR: 1.13, 95% CI: 1.03 - 1.24, p = 0.0094) among the patients with IBD were observed when compared with the controls. Other independent factors associated with corneal surface damage were age (aHR: 1.003), sex (male vs. female, aHR: 0.85), and monthly insurance premium (501-800 vs. 0-500 U.S. dollars, aHR: 1.45; ≥ 801 vs. 0-500 U.S. dollars, aHR: 1.32). CONCLUSIONS: Our results suggested that IBD was an independent risk factor for DED and ocular surface damage. Clinical strategies are needed to prevent visual impairment or losses in these susceptible patients.

Cigarette smoking, opioid consumption, and pain intensity after major surgery: An observational study.

BACKGROUND: Chronic exposure to nicotine may change pain perception and promote opioid intake. This study aimed to evaluate the putative effect of cigarette smoking on opioid requirements and pain intensity after surgery. METHODS: Patients who underwent major surgery and received intravenous patient-controlled analgesia (IV-PCA) at a medical center between January 2020 and March 2022 were enrolled. Patients' preoperative smoking status was assessed using a questionnaire by certified nurse anesthetists. The primary outcome was postoperative opioid consumption within 3 days after surgery. The secondary outcome was the mean daily maximum pain score, assessed using a self-report 11-point numeric rating scale, and the number of IV-PCA infusion requests within three postoperative days. Multivariable linear regression models were used to calculate the regression coefficient (beta) and 95% confidence interval (CI) for the association between smoking status and outcomes of interest. RESULTS: A total of 1162 consecutive patients were categorized into never smokers (n = 968), former smokers (n = 45), and current smokers (n = 149). Current smoking was significantly associated with greater postoperative opioid consumption (beta: 0.296; 95% CI, 0.068-0.523), higher pain scores (beta: 0.087; 95% CI, 0.009-0.166), and more infusion requests (beta: 0.391; 95% CI, 0.073-0.710) compared with never smokers. In a dose-dependent manner, smoking quantity (cigarette per day) was positively correlated with both intraoperative (Spearman's rho: 0.2207, p = 0.007) and postoperative opioid consumption (Spearman's rho: 0.1745, p = 0.033) among current smokers. CONCLUSION: Current cigarette smokers experienced higher acute pain, had more IV-PCA infusion requests, and consumed more opioids after surgery. Multimodal analgesia with nonopioid analgesics and opioid-sparing techniques, along with smoking cessation should be considered for this population.

Rheumatoid Arthritis Associated with Dry Eye Disease and Corneal Surface Damage: A Nationwide Matched Cohort Study.

Rheumatoid arthritis is potentially connected to ocular disorders, such as corneal inflammation and lacrimal gland destruction. This study aimed to evaluate the risk of dry eye disease (DED) and corneal surface damage among patients with rheumatoid arthritis. In a nationwide cohort study, we utilized Taiwan's National Health Insurance research database and conducted propensity score matching to compare the risks of DED and corneal surface damage between patients with and without rheumatoid arthritis. Proportional hazards regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the outcomes of interest. The matching procedure generated 33,398 matched pairs with 501,377 person-years of follow-up for analyses. The incidence of DED was 23.14 and 10.25 per 1000 person-years in patients with and without rheumatoid arthritis, respectively. After adjusting for covariates, rheumatoid arthritis was significantly associated with DED (aHR: 2.03, 95% CI: 1.93−2.13, p < 0.0001). The association was generally consistent across the subgroups of age, sex, use of systemic corticosteroids, and different comorbidity levels. In addition, patients with rheumatoid arthritis had a higher risk of corneal surface damage (aHR: 1.36, 95% CI: 1.21−1.51, p < 0.0001) compared to control subjects. Other independent factors for corneal surface damage were age and sleeping disorders. Rheumatoid arthritis was associated with an increased risk of DED and corneal surface damage. Ophthalmological surveillance is required to prevent vision-threatening complications in this susceptible population.

Ultrasensitive Detection of Interleukin 6 by Using Silicon Nanowire Field-Effect Transistors.

Interleukin 6 (IL-6) has been regarded as a biomarker that can be applied as a predictor for the severity of COVID-19-infected patients. The IL-6 level also correlates well with respiratory dysfunction and mortality risk. In this work, three silanization approaches and two types of biorecognition elements were used on the silicon nanowire field-effect transistors (SiNW-FETs) to investigate and compare the sensing performance on the detection of IL-6. Experimental data revealed that the mixed-SAMs-modified silica surface could have superior surface morphology to APTES-modified and APS-modified silica surfaces. According to the data on detecting various concentrations of IL-6, the detection range of the aptamer-functionalized SiNW-FET was broader than that of the antibody-functionalized SiNW-FET. In addition, the lowest concentration of valid detection for the aptamer-functionalized SiNW-FET was 2.1 pg/mL, two orders of magnitude lower than the antibody-functionalized SiNW-FET. The detection range of the aptamer-functionalized SiNW-FET covered the concentration of IL-6, which could be used to predict fatal outcomes of COVID-19. The detection results in the buffer showed that the anti-IL-6 aptamer could produce better detection results on the SiNW-FETs, indicating its great opportunity in applications for sensing clinical samples.

Morphometric and ultrasonographic determinants of difficult laryngoscopy in obese patients: A prospective observational study.

BACKGROUND: Obese people have a higher risk of difficult laryngoscopy due to their thick neck, large tongue, and redundant pharyngeal soft tissue. However, there is still no established predictive factor for difficult laryngoscopy in obese population. METHODS: We conducted a prospective assessor-blind observational study to enroll adult patients with a body mass index of 30 kg·m-2 or higher undergoing laparoscopic sleeve gastrectomy at a medical center between May 2020 and August 2021. Conventional morphometric characteristics along with ultrasonographic airway parameters were evaluated before surgery. The primary outcome was difficult laryngoscopy, defined as a Cormack and Lehane's grade III or IV during direct laryngoscopy. Logistic regression analyses were performed to evaluate the association between included factors and difficult laryngoscopy. Discrimination performance of predictive factors was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: A total of 80 patients were evaluated, and 17 (21.3%) developed an event of difficult laryngoscopy. Univariate analyses identified five factors associated with difficult laryngoscopy, including age, sex, hypertension, neck circumference, and cross-sectional area of tongue base. After adjusting for these variables, neck circumference was the only independent influential factor, adjusted odds ratio: 1.227 (95% confidence interval, 1.009-1.491). Based on Youden's index, the optimal cutoff of neck circumference was 49.1 cm with AUC: 0.739 (sensitivity: 0.588, specificity: 0.889; absolute risk difference: 0.477, and number needed to treat: 3). CONCLUSION: Greater neck circumference was an independent risk factor for difficult laryngoscopy in obese patients. This finding provides a way of reducing unanticipated difficult airway in this high-risk population.

Spectral Entropy Monitoring Accelerates the Emergence from Sevoflurane Anesthesia in Thoracic Surgery: A Randomized Controlled Trial.

The clinical efficacy of spectral entropy monitoring in improving postoperative recovery remains unclear. This trial aimed to investigate the impact of M-Entropy (GE Healthcare, Helsinki, Finland) guidance on emergence from anesthesia and postoperative delirium in thoracic surgery. Adult patients undergoing video-assisted thoracoscopic surgery for lung resection at a medical center were randomly allocated into the M-Entropy guidance group (n = 39) and the control group (n = 37). In the M-Entropy guidance group, sevoflurane anesthesia was titrated to maintain response and state entropy values between 40 and 60 intraoperatively. In the control group, the dosing of sevoflurane was adjusted based on clinical judgment and vital signs. The primary outcome was time to spontaneous eye opening. M-Entropy guidance significantly reduced the time proportion of deep anesthesia (entropy value <40) during surgery, mean difference: −21.5% (95% confidence interval (CI): −32.7 to −10.3) for response entropy and −24.2% (−36.3 to −12.2) for state entropy. M-Entropy guidance significantly shortened time to spontaneous eye opening compared to clinical signs, mean difference: −154 s (95% CI: −259 to −49). In addition, patients of the M-Entropy group had a lower rate of emergence agitation (absolute risk reduction: 0.166, 95% CI: 0.005−0.328) and delirium (0.245, 0.093−0.396) at the postanesthesia care unit. M-Entropy-guided anesthesia hastened awakening and potentially prevented emergence agitation and delirium after thoracic surgery. These results may provide an implication for facilitating postoperative recovery and reducing the complications associated with delayed emergence and delirium.

A Comparison of Oxygenation Efficacy between High-Flow Nasal Cannulas and Standard Facemasks during Elective Tracheal Intubation for Patients with Obesity: A Randomized Controlled Trial.

Obese patients are predisposed to rapid oxygen desaturation during tracheal intubation. We aimed to compare the risk of desaturation between high-flow nasal oxygenation (HFNO) and classical facemask oxygenation (FMO) during rapid sequence intubation for elective surgery in obese patients. Adults with a body mass index ≥30 kg·m−2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into the HFNO group (n = 40) and FMO group (n = 40). In the HFNO group, patients used a high-flow nasal cannula to receive 30 to 50 L·min−1 flow of heated and humidified 100% oxygen. In the FMO group, patients received a fitting facemask with 15 L·min−1 flow of 100% oxygen. After 5-min preoxygenation, rapid sequence intubation was performed. The primary outcome was arterial desaturation during intubation, defined as a peripheral capillary oxygen saturation (SpO2) <92%. The risk of peri-intubation desaturation was significantly lower in the HFNO group compared to the FMO group; absolute risk reduction: 0.20 (95% confidence interval: 0.05−0.35, p = 0.0122); number needed to treat: 5. The lowest SpO2 during intubation was significantly increased by HFNO (median 99%, interquartile range: 97−100) compared to FMO (96, 92−100, p = 0.0150). HFNO achieved a higher partial pressure of arterial oxygen (PaO2) compared to FMO, with medians of 476 mmHg (interquartile range: 390−541) and 397 (351−456, p = 0.0010), respectively. There was no difference in patients' comfort level between groups. Compared with standard FMO, HFNO with apneic oxygenation reduced arterial desaturation during tracheal intubation and enhanced PaO2 among patients with obesity.

Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress.

Aims: We examined the change in endogenous hydrogen sulfide (H2S) production and its role in sepsis-induced myocardial dysfunction (SIMD). Results: Significant elevations in plasma cardiac troponin I (cTnI), creatine kinase (CK), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were noted in SIMD patients, whereas left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and plasma H2S were significantly decreased relative to those in the controls. Plasma H2S was linearly related to LVEF and LVFS. Subsequently, an SIMD model was developed in mice by injecting lipopolysaccharide (LPS), and NaHS, an H2S donor, was used to elucidate the pathophysiological role of H2S. The mice showed decreased ventricular function and increased levels of TNF-α, IL-1ß, cTnI, and CK after LPS injections. Toll-like receptor (TLR) 4 protein and endoplasmic reticulum stress (ERS) proteins were over expressed in the SIMD mice. All of the parameters above showed more noticeable variations in cystathionine γ-lyase knockout mice relative to those in wild type mice. The administration of NaHS could improve ventricular function and attenuate inflammation and ERS in the heart. Conclusion: Overall, these findings indicated that endogenous H2S deficiency contributed to SIMD and exogenous H2S ameliorated sepsis-induced myocardial dysfunction by suppressing inflammation and ERS via inhibition of the TLR4 pathway.

A comparison of prognostic performance of perioperative inflammation markers in surgical resection for hepatocellular carcinoma.

BACKGROUND: Systemic inflammation correlates closely with tumor invasion and may predict survival in cancer patients. We aimed to compare the prognostic value of various inflammation-based markers in patients with hepatocellular carcinoma. METHODS: We consecutively enrolled 1450 patients with primary hepatocellular carcinoma undergoing surgical resection at the medical center between 2005 and 2016 and assessed them through September 2018. Prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative dynamic changes were analyzed regarding their predictive ability of postoperative disease-free survival and overall survival. We calculated the adjusted hazard ratio (HR) and 95% CI of the association between inflammation-based markers and survival using multiple Cox proportional hazards models. Youden's index of receiver operating characteristics curves was used to determine optimal cut-off points. RESULTS: Prognostic nutritional index was an independent predictor for both disease-free survival (<50.87 vs ≥50.87, HR: 1.274, 95% CI, 1.071-1.517, p = 0.007) and overall survival (<46.65 vs ≥46.65, HR: 1.420, 95% CI, 1.096-1.842, p = 0.008). Besides, the relative change of neutrophil-to-lymphocyte ratio predicted overall survival (<277% vs ≥277%, HR: 1.634, 95% CI, 1.266-2.110, p < 0.001). Combination of both markers offered better prognostic performance for overall survival than either alone. Body mass index, liver cirrhosis, chronic kidney disease, and tumor diameter were significantly associated with both markers. CONCLUSION: Prognostic nutritional index and perioperative relative change of neutrophil-to-lymphocyte ratio independently predict postoperative survival in patients undergoing surgical resection of hepatocellular carcinoma. These results provided important evidence for risk stratification and individualized anti-cancer therapy.

Recovery Profiles of Sevoflurane and Desflurane with or without M-Entropy Guidance in Obese Patients: A Randomized Controlled Trial.

Obesity increases the risk of prolonged emergence from general anesthesia due to the delayed release of anesthetic agents from body fat. This trial aimed to evaluate the effects of sevoflurane and desflurane along with anesthetic depth monitoring on emergence time from anesthesia in obese patients. Adults with a body mass index ≥ 30 kg·m-2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into four groups: sevoflurane or desflurane anesthesia with or without M-Entropy guidance on anesthetic depth in a ratio of 1:1:1:1. In the M-Entropy guidance groups, the dosage of sevoflurane and desflurane was adjusted to achieve response and state entropy values between 40 and 60 during surgery. In the non-M-Entropy guidance groups, the dosage of anesthetics was titrated according to clinical signs. Primary outcome was time to spontaneous eye opening. A total of 80 participants were randomized. Compared to sevoflurane, desflurane anesthesia significantly reduced the time to spontaneous eye opening [mean difference (MD): -129 s; 95% confidence interval (CI): -211, -46], obeying commands (-160; -243, -77), tracheal extubation (-172; -266, -78), and leaving operating room (-148; -243, -54). M-Entropy guidance further reduced time to eye opening (MD: -142 s; 99.2% CI: -276, -8), tracheal extubation (-199; -379, -19), and leaving operating room (-190; -358, -23) in the desflurane but not the sevoflurane group. M-Entropy guidance significantly reduced the risk of agitation during emergence, i.e., risk difference: -0.275 (95% CI: -0.464, -0.086); and number needed to treat: 4. Compared to sevoflurane, using desflurane to maintain general anesthesia accelerated the return of consciousness in obese patients. M-Entropy guidance further hastened awakening in patients using desflurane and prevented emergence agitation.

A comparison of inflammation markers for predicting oncological outcomes after surgical resection of non-small-cell lung cancer: a validated analysis of 2,066 patients.

Clinical and pathological predictors have proved to be insufficient in identifying high-risk patients who develop cancer recurrence after tumour resection. We aimed to compare the prognostic ability of various inflammation markers in patients undergoing surgical resection of lung cancer. We consecutively included 2,066 patients with stage I-III non-small-cell lung cancer undergoing surgical resection at the center between 2005 and 2015. We evaluated prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative changes. We conducted stepwise backward variable elimination and internal validation to compare the selected markers' predictive performance for postoperative recurrence-free survival and overall survival. Preoperative neutrophil-to-lymphocyte ratio independently predicts recurrence-free survival (HR: 1.267, 95% CI 1.064-1.509, p = 0.0079, on base-2 logarithmic scale) and overall survival (HR: 1.357, 95% CI 1.070-1.721, p = 0.0117, on base-2 logarithmic scale). The cut-off value is 2.3 for predicting both recurrence (sensitivity: 46.1% and specificity: 66.7%) and mortality (sensitivity: 84.2% and specificity: 40.4%). Advanced cancer stage, poor tumour differentiation, and presence of perineural infiltration were significantly correlated with higher preoperative neutrophil-to-lymphocyte ratio. We concluded that preoperative neutrophil-to-lymphocyte ratio is superior to prognostic nutritional index and platelet-to-lymphocyte ratio in predicting postoperative recurrence and mortality of patients undergoing surgical resection of non-small-cell lung cancer.

Preexisting Dementia Is Associated with Increased Risks of Mortality and Morbidity Following Major Surgery: A Nationwide Propensity Score Matching Study.

Patients with dementia are predisposed to multiple physiological abnormalities. It is uncertain if dementia associates with higher rates of perioperative mortality and morbidity. We used reimbursement claims data of Taiwan's National Health Insurance and conducted propensity score matching analyses to evaluate the risk of mortality and major complications in patients with or without dementia undergoing major surgery between 2004 and 2013. We applied multivariable logistic regressions to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the outcome of interest. After matching to demographic and clinical covariates, 7863 matched pairs were selected for analysis. Dementia was significantly associated with greater risks of 30-day in-hospital mortality (aOR: 1.71, 95% CI: 1.09-2.70), pneumonia (aOR: 1.48, 95% CI: 1.16-1.88), urinary tract infection (aOR: 1.59, 95% CI: 1.30-1.96), and sepsis (OR: 1.77, 95% CI: 1.34-2.34) compared to non-dementia controls. The mortality risk in dementia patients was attenuated but persisted over time, 180 days (aOR: 1.49, 95% CI: 1.23-1.81) and 365 days (aOR: 1.52, 95% CI: 1.30-1.78) after surgery. Additionally, patients with dementia were more likely to receive blood transfusion (aOR: 1.32, 95% CI: 1.11-1.58) and to need intensive care (aOR: 1.40, 95% CI: 1.12-1.76) compared to non-dementia controls. Senile dementia and Alzheimer's disease were independently associated with higher rates of perioperative mortality and complications, but vascular dementia was not affected. We found that preexisting dementia was associated with mortality and morbidity after major surgery.

Hospitalization outcome of heart diseases between patients who received medical care by cardiologists and non-cardiologist physicians: A propensity-score matched study.

BACKGROUND AND AIMS: The effects of physician specialty on the outcome of heart disease remains incompletely understood because of inconsistent findings from some previous studies. Our purpose is to compare the admission outcomes of heart disease in patients receiving care by cardiologists and noncardiologist (NC) physicians. METHODS: Using reimbursement claims data of Taiwan's National Health Insurance from 2008-2013, we conducted a matched study of 6264 patients aged ≥20 years who received a cardiologist's care during admission for heart disease. Using a propensity score matching procedure adjusted for sociodemographic characteristics, medical condition, and type of heart disease, 6264 controls who received an NC physician's care were selected. Logistic regressions were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for complications and mortality during admission for heart disease associated with a cardiologist's care. RESULTS: Patients who received a cardiologist's care had a lower risk of pneumonia (OR = 0.61; 95% CI, 0.53-0.70), septicemia (OR = 0.49; 95% CI, 0.39-0.61), urinary tract infection (OR = 0.76; 95% CI, 0.66-0.88), and in-hospital mortality (OR = 0.37; 95% CI, 0.29-0.47) than did patients who received an NC physician's care. The association between a cardiologist's care and reduced adverse events following admission was significant in both sexes and in patients aged ≥40 years. CONCLUSION: We raised the possibility that cardiologist care was associated with reduced infectious complications and mortality among patients who were admitted due to heart disease.

Magnetic immunoassay using CdSe/ZnS quantum dots as fluorescent probes to detect the level of DNA methyltransferase 1 in human serum sample.

BACKGROUND: DNA methyltransferase 1 (DNMT1), a dominant enzyme responsible for the transfer of a methyl group from the universal methyl donor to the 5-position of cytosine residues in DNA, is essential for mammalian development and closely related to cancer and a variety of age-related chronic diseases. DNMT1 has become a useful biomarker in early disease diagnosis and a potential therapeutic target in cancer therapy and drug development. However, till now, most of the studies on DNA methyltransferase (MTase) detection have focused on the prokaryote MTase and its activity. METHODS: A magnetic fluorescence-linked immunosorbent assay (FLISA) using CdSe/ZnS quantum dots as fluorescent probes was proposed for the rapid and sensitive detection of the DNMT1 level in this study. Key factors that affect the precision and accuracy of the determination of DNMT1 were optimized. RESULTS: Under the optimal conditions, the limit of detection was 0.1 ng/mL, the linear range was 0.1-1,500 ng/mL, the recovery was 91.67%-106.50%, and the relative standard deviations of intra- and inter-assays were respectively 5.45%-11.29% and 7.03%-11.25%. The cross-reactivity rates with DNA methyltransferases 3a and 3b were only 4.0% and 9.4%, respectively. Furthermore, FLISA was successfully used to detect the levels of DNMT1 in human serum samples, and compared with commercial enzyme-linked immunosorbent assay (ELISA) kits. The results revealed that there was a good correlation between FLISA and commercial ELISA kits (correlation coefficient r=0.866, p=0.001). The linear scope of FLISA was broader than ELISA, and the measurement time was much shorter than ELISA kits. CONCLUSION: These indicated that the proposed FLISA method was sensitive and high throughput and can quickly screen the level of DNMT1 in serum samples.

Hydrogen sulfide improves endothelial dysfunction in hypertension by activating peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase signaling.

OBJECTIVE: We aimed to elucidate the ameliorative effect of hydrogen sulfide (H2S) on endothelium-dependent relaxation disturbances via peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase (PPARδ/eNOS) pathway activation in hypertensive patients and rats. METHODS: Renal arteries were collected from normotensive and hypertensive patients who underwent nephron-sparing surgery. Renal arteries from 37 patients were cultured with or without sodium H2S (NaHS) 50 µmol/l. The rats were randomly divided into four groups: Sham; Sham + NaHS, two kidneys; one clipped (2K1C); and 2K1C + NaHS. Mean arterial pressure was measured by tail-cuff plethysmography. A microvessel recording technique was used to observe the effect of NaHS on endothelium-dependent relaxation. Plasma H2S concentrations were detected using the monobromobimane method. Real-time PCR and western blotting were used to assess mRNA and protein levels of AT1, cystathionine γ-lyase, PPARδ, and phosphor-eNOS. Laser confocal scanning microscopy measured intracellular NO production in human umbilical vein endothelial cells. RESULTS: NaHS improved endothelial function in hypertensive humans and rats. The 20-week administration of NaHS to 2K1C rats lowered the mean arterial pressure. In human umbilical vein endothelial cells, NaHS improved the AngII-induced production of NO. NaHS upregulated PPARδ expression, increased protein kinase B (Akt) or adenosine monophosphate kinase-activated protein kinase (AMPK) phosphorylation, and enhanced eNOS phosphorylation. A PPARδ agonist could mimic the ameliorative effect of NaHS that was suppressed by PPARδ, AMPK, or Akt inhibition. CONCLUSION: H2S plays a protective function in renal arterial endothelium in hypertension by activating the PPARδ/PI3K/Akt/eNOS or PPARδ/AMPK/eNOS pathway. H2S may serve as an effective strategy against hypertension.

Hydrogen Sulfide Improves Myocardial Remodeling via Downregulated Angiotensin â ¡/AT1R Pathway in Renovascular Hypertensive Rats.

BACKGROUND: Hydrogen sulfide (H2S) is an important endogenous gaseous transmitter in many physiological functions. Plasma H2S decreased, and angiotensin II (Ang II) type 1 receptor (AT1R) increased in the myocardial tissues in 2-kidney 1-clip (2K1C) rats than in normotensive rats. Accumulating evidences suggest that H2S inhibited Ang II/AT1R pathway to regulate cardiovascular function. Therefore, we hypothesized that H2S may exert beneficial effects on myocardial remodeling in 2K1C rat models of renovascular hypertension. METHODS AND RESULTS: Sodium hydrosulfide (NaHS, 56 µmol/kg/day) was administered intraperitoneally to the rats from the 7th day after 2K1C operation. Systolic blood pressure was significantly increased from the first week after the operation and was lowered after NaHS treatment for 4 weeks. H2S could also inhibit the ratio of left ventricle and septum weight to body weight, improve cross-sectional area, and ameliorate ventricular dysfunction. Additionally, the protein expression of AT1R and Ang II serum content were downregulated, whereas superoxide dismutase (SOD) protein was upregulated in 2K1C rats by NaHS treatment for 4 weeks. Furthermore, the reactive oxygen species level and AT1R protein were increased, whereas SOD protein was decreased in cardiomyocytes treated with Ang II compared with the control group. NaHS could reverse these changes. Losartan and N-acetylcysteine could also reverse Ang II-induced changes. CONCLUSIONS: The protective effect of H2S is attributable to the suppression of oxidative stress. This process involves the inhibition of the Ang II/AT1R pathway and upregulation of antioxidant enzymes in 2K1C rats.

Hydrogen Sulfide Improves Endothelial Dysfunction via Downregulating BMP4/COX-2 Pathway in Rats with Hypertension.

Aims. We object to elucidate that protective effect of H2S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56 µmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from 199.9 ± 3.312 mmHg to 159.4 ± 5.434 mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats. 2K1C reduced CSE level twofold, decreased plasma levels of H2S about 6-fold, increased BMP4, Nox2, and Nox4 levels 2-fold and increased markers of oxidative stress MDA and nitrotyrosine 1.5-fold, upregulated the expression of phosphorylation-p38 MAPK 2-fold, and increased protein levels of COX-2 1.5-fold, which were abolished by NaHS treatment. Conclusions. Our results demonstrate that H2S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H2S on endothelial impairment. These results throw light on endothelial protective effect of H2S and provide new target for prevention and therapy of hypertension.

Hydrogen Sulfide Improves Vascular Calcification in Rats by Inhibiting Endoplasmic Reticulum Stress.

In this study, the vitamin D3 plus nicotine (VDN) model of rats was used to prove that H2S alleviates vascular calcification (VC) and phenotype transformation of vascular smooth muscle cells (VSMC). Besides, H2S can also inhibit endoplasmic reticulum stress (ERS) of calcified aortic tissues. The effect of H2S on alleviating VC and phenotype transformation of VSMC can be blocked by TM, while PBA also alleviated VC and phenotype transformation of VSMC that was similar to the effect of H2S. These results suggest that H2S may alleviate rat aorta VC by inhibiting ERS, providing new target and perspective for prevention and treatment of VC.

Upregulation of spinal NMDA receptors mediates hydrogen sulfide-induced hyperalgesia.

Hydrogen sulfide (H2S) is an endogenous neurotransmitter that importantly regulates various physiological and pathological events including pain signal transduction. In this study, we investigated the role of spinal NMDA receptors in the nociception induced by intraplantar injection of NaHS, an H2S donor. Intraplantar injection of NaHS into hindpaw significantly decreased the paw withdrawal threshold (PWT) in contralateral hindpaw. However, intraplantar formalin injection did not produce PWT in contralateral hindpaw. Intrathecal injection of methemoglobin, a H2S scavenger, abolished hyperalgesia induced by NaHS. In addition, NaHS-induced hyperalgesia was partly, but significantly, attenuated by intrathecal injection of hydroxylamine, a cystathionine-ß-synthase (CBS) inhibitor. RT-PCR and western blotting analysis revealed that NR2B mRNA and protein levels were increased in the spinal dorsal horn, but not in dorsal root ganglion (DRG) in rats subjected to NaHS intraplantar injection. Collectively, these data suggest that peripheral injection of H2S donor causes hyperalgesia through increase in NR2B expression and production of H2S in the spinal cord.