The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

OBJECTIVES: This study aimed to observe the color rebound and rebound rates of non-pulp discolored teeth within 1 year after routine internal bleaching to guide clinical practice and prompt prognosis. METHODS: In this work, the efficacy of bleaching was observed in 20 patients. The color of discolored teeth was measured by using a computerized colorimeter before bleaching; immediately after bleaching; and at the 1st, 3rd, 6th, 9th, and 12th months after bleaching. The L*, a*, and b* values of the color of cervical, mesial, and incisal parts of the teeth were obtained, and the color change amounts ΔE*, ΔL*, Δa*, and Δb* were calculated. The overall rebound rate (P*) and the color rebound velocity (V*) were also analyzed over time. RESULTS: In 20 patients following treatment, the average ΔE* of tooth color change was 14.99. After bleaching, the neck and middle of the teeth ΔE* and ΔL* decreased in the 1st, 3rd, 6th, 9th, and 12th months, and the differences were statistically significant. Meanwhile, from the 9th month after bleaching, the rebound speed was lower than that in the 1st month, and the difference was statistically significant. The incisal end of the tooth ΔE* and ΔL* decreased in the 6th, 9th, and 12th months after bleaching, and the differences were statistically significant. No significant difference was found in the rebound speed between time points. However, this rate settled after the 9th month, with an average color rebound rate of 30.11% in 20 patients. CONCLUSIONS The results indicated that internal bleaching could cause a noticeable color change on pulpless teeth. The color rebound after bleaching was mainly caused by lightness (L*), which gradually decreased with time, and it was slightly related to a* and b*. The color of the teeth after internal bleaching rebounded to a certain extent with time, but the color rebound speed became stable from the 9th month. Clinically, secondary internal bleaching can be considered at this time according to whether the colors of the affected tooth and the adjacent tooth are coordinated and depending on the patient's needs.
Humans ; Tooth Bleaching/methods* ; Tooth, Nonvital/drug therapy* ; Color ; Tooth Discoloration/drug therapy* ; Tooth ; Hydrogen Peroxide/therapeutic use* ; Tooth Bleaching Agents/therapeutic use*

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.
Acute Lung Injury ; Aging ; Animals ; Anti-Inflammatory Agents ; Antioxidants/chemistry* ; Asthma/therapy* ; Autophagy ; COVID-19/therapy* ; Humans ; Hydrogen/therapeutic use* ; Hypertension, Pulmonary/therapy* ; Inflammation ; Lung Diseases/therapy* ; Lung Neoplasms/therapy* ; Mice ; Oxidative Stress ; Pulmonary Disease, Chronic Obstructive/therapy* ; Pulmonary Fibrosis/therapy* ; Pyroptosis ; Reactive Oxygen Species

Animals ; Antioxidants/therapeutic use* ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies/drug therapy* ; Humans ; Hydrogen/therapeutic use* ; Kidney

ObjectiveHydrogen sulfide (HS), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that HS regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that HS targets cardiomyocyte autophagy to regulate cardiovascular function.

Data SourcesThis review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases."

Study SelectionOriginal articles and critical reviews on HS and autophagy were selected for this review.

ResultsWhen autophagy plays an adaptive role in the pathogenesis of diseases, HS restores autophagy; otherwise, when autophagy plays a detrimental role, HS downregulates autophagy to exert a cardioprotective function. For example, HS has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. HS postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy.

ConclusionsHS exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of HS therapy for cardiovascular diseases.

Animals ; Autophagy ; drug effects ; Cardiovascular Diseases ; prevention & control ; Cardiovascular System ; cytology ; drug effects ; Humans ; Hydrogen Sulfide ; therapeutic use ; Myocytes, Cardiac ; cytology ; drug effects

OBJECTIVEVigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay.

METHODSGastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GP), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined.

RESULTSPretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GP were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group.

CONCLUSIONThe study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.

Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Aspirin ; Edema ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Gastrointestinal Agents ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hydrogen-Ion Concentration ; Leukocytes ; Male ; Malondialdehyde ; metabolism ; Mucus ; metabolism ; Nuts ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Severity of Illness Index ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Vigna

Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and anti-inflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root (ICR) were measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by HO or NaSO in H9c2 cardiomyocytes, followed by increasing the SOD activities and decreasing the MDA and ROS levels. In addition, it could suppress the apoptosis of cardiomyocytes. In the rat model of myocardial ischemia, ICR decreased myocardial infarct size and suppressed the activities of LDH and CK. Furthermore, ICR attenuated histopathological alterations of heart tissues and the MDA levels, while increasing SOD activities in serum. In conclusion, these results suggest that ICR has cardioprotective activity and could be developed as a new food supplement for the prevention of ischemic heart disease.
Animals ; Antioxidants ; metabolism ; pharmacology ; therapeutic use ; Apoptosis ; Cardiovascular Agents ; pharmacology ; therapeutic use ; Cell Survival ; drug effects ; Hydrogen Peroxide ; metabolism ; Ilex ; Malondialdehyde ; metabolism ; Myocardial Infarction ; Myocardial Ischemia ; drug therapy ; metabolism ; pathology ; Myocardium ; cytology ; pathology ; Myocytes, Cardiac ; drug effects ; Oxidative Stress ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.
Chest Pain ; etiology ; Esophagus ; drug effects ; Gastroenterology ; methods ; Gastroesophageal Reflux ; diagnosis ; drug therapy ; Heartburn ; diagnosis ; drug therapy ; Humans ; Hydrogen-Ion Concentration ; Life Style ; Primary Health Care ; Proton Pump Inhibitors ; therapeutic use ; Surveys and Questionnaires

: There is limited data on paediatric resuscitation outcomes in Asia. We aimed to describe outcomes of paediatric in-hospital cardiac arrests (IHCA) and peri-resuscitation factors associated with mortality in our institution.: Using data from our hospital's code registry from 2009 to 2014, we analysed all patients younger than 18 years of age with IHCA who required cardiopulmonary resuscitation (CPR). Exposure variables were obtained from clinical demographics, CPR and post-resuscitation data. Outcomes measured were: survival after initial CPR event and survival to hospital discharge. We analysed categorical and continuous variables with Fisher's exact and Wilcoxon rank- sum tests respectively. Statistical significance was taken as<0.05.: We identified 51 patients in the study period. Median age of patients was 1.9 (interquartile range [IQR]: 0.3, 5.5) years. Twenty-six (51%) patients had bradycardia as the first-recorded rhythm. The most common pre-existing medical condition was respiratory-related (n = 25, 48%). Thirty-eight (75%) achieved sustained return of spontaneous circulation, 24 (47%) survived to paediatric intensive care unit (PICU) discharge and 23 (45%) survived to hospital discharge. Risk factors for hospital mortality included: age, duration of CPR, adrenaline, calcium or bicarbonate administration during CPR, Paediatric Index of Mortality (PIM)- II scores, first recorded post-resuscitation pH and hyperglycaemia within 24 hours of resuscitation.: We demonstrated an association between clinical demographics (age, PIM-II scores), CPR variables (duration of CPR and administration of adrenaline, calcium or bicarbonate) and post-resuscitation laboratory results (first recorded pH and hyperglycaemia within 24 hours) with PICU survival. The availability and quality of post- resuscitation care may have implications on survival after paediatric IHCA.
Adolescent ; Bicarbonates ; therapeutic use ; Calcium ; therapeutic use ; Cardiopulmonary Resuscitation ; methods ; Child ; Child, Preschool ; Epinephrine ; therapeutic use ; Female ; Heart Arrest ; mortality ; therapy ; Humans ; Hydrogen-Ion Concentration ; Hyperglycemia ; epidemiology ; Infant ; Infant, Newborn ; Male ; Patient Discharge ; Retrospective Studies ; Risk Factors ; Singapore ; epidemiology ; Survival Rate ; Sympathomimetics ; therapeutic use

OBJECTIVETo investigate the regulatory effects of Shenfu Injection (SFI, ) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure (CHF).

METHODSForty-five healthy Wistar rats were randomized into three groups: sham, heart failure (model) and SFI group. The CHF was induced by left coronary artery ligation. Seven days after the surgical operation, animals in the sham group and the model group received saline (6.2 mL/kg/d), while animals in the SFI group received SFI (6.2 mL/kg d) intraperitoneally. Four weeks later, cardiac hemodynamic parameters were measured via the carotid route. The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS).

RESULTSRecording of hemodynamic parameters showed that left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure (+dp/dtmax) rise, and maximum rate of left ventricular pressure (-dp/dtmax) decrease, while the left ventricular end diastolic pressure (LVEDP) rose in the model group compared to those in the sham group (P <0.05). The results of the MALDI-TOF MS indicated that haptoglobin (HP), pentraxin 3 (PTX3) and alpha-1-antitrypsin were up-regulated, while serum albumin and 40S ribosomal protein were down-regulated in the model group (P <0.05). Compared with the model group, LVSP, +dp/dtmax and -dp/dtmax were higher, while LVEDP was lower in the SFI group (P<0.05). Expression levels of HP and PTX3 were lower than in the model group (P<0.05).

CONCLUSIONSFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF. The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure, and they could also be the serum protein targets of SFI.

Animals ; Blood Proteins ; metabolism ; C-Reactive Protein ; metabolism ; Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Electrophoresis, Gel, Two-Dimensional ; Haptoglobins ; metabolism ; Heart Failure ; blood ; complications ; drug therapy ; physiopathology ; Heart Function Tests ; Hemodynamics ; Hydrogen-Ion Concentration ; Imaging, Three-Dimensional ; Inflammation ; complications ; drug therapy ; Male ; Myocardial Ischemia ; blood ; complications ; drug therapy ; physiopathology ; Phytotherapy ; Proteome ; metabolism ; Rats, Wistar ; Serum Amyloid P-Component ; metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization