Cloning and functional characterization of thioredoxin gene from kuruma shrimp Marsupenaeus japonicus.

As an important disulfide reductase of the intracellular antioxidant system, Thioredoxin (Trx) plays an important role in maintaining oxidative stress balance and protecting cells from oxidative damage. In recent years, there is increasing evidence that Trx is a key molecule in the pathogenesis of various diseases and a potential therapeutic target for major diseases including lung, colon, cervical, gastric and pancreatic cancer. However, few knowledge is known about the function of Trx in virus infection. In this study, we reported the cloning and functional investigation of a Trx homologue gene, named MjTrx, in shrimp Marsupenaeus japonicus suffered white spot syndrome virus (WSSV) infection. MjTrx is a 105-amino acid polypeptide with a conservative Cys-Gly-Pro-Cys motif in the catalytic center. Phylogenetic trees analysis showed that MjTrx has a higher relationship with Trx from other invertebrate and clustered with Trx1 from arthropod. MjTrx transcripts is abundant in the gill and intestine tissues and can be detected in the hemocytes, heart, stomach, and hepatopancreas tissues. The transcription levels of MjTrx in hemocytes, gills and intestine tissues of shrimp were significantly up-regulated after white spot syndrome virus infection. MjTrx was recombinant expressed in vitro and exhibited obvious disulfide reductase activity. In addition, overexpression MjTrx in shrimp resulted in the increase of hydrogen peroxide (H2O2) concentration in vivo. All these results strongly suggested that MjTrx functioned in redox homeostasis regulating and played an important role in shrimp antiviral immunity.

Role of HGF/c-Met in the treatment of colorectal cancer with liver metastasis.

The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

Protective Effects of Hydrogen-Rich Saline Against Lipopolysaccharide-Induced Alveolar Epithelial-to-Mesenchymal Transition and Pulmonary Fibrosis.

BACKGROUND Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. MATERIAL AND METHODS Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels. Development of epithelial-to-mesenchymal transition (EMT) was identified by examining protein expressions of E-cadherin and α-smooth muscle actin (α-SMA). Transforming growth factor (TGF)-ß1 content, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, catalase (CAT), and superoxide dismutase (SOD) activity were determined. RESULTS Mice exhibited increases in collagen deposition, hydroxyproline, type I collagen contents, and TGF-ß1 production in lung tissues after LPS treatment. LPS-induced lung fibrosis was associated with increased expression of α-SMA, as well as decreased expression of E-cadherin. In addition, LPS treatment increased MDA levels but decreased T-AOC, CAT, and SOD activities in lung tissues, indicating that LPS induced pulmonary oxidative stress. Hydrogen-rich saline treatment at doses of 2.5, 5, or 10 ml/kg significantly attenuated LPS-induced pulmonary fibrosis. LPS-induced loss of E-cadherin in lung tissues was largely reversed, whereas the acquisition of α-SMA was dramatically decreased by hydrogen-rich saline treatment. In addition, hydrogen-rich saline treatment significantly attenuated LPS-induced oxidative stress. CONCLUSIONS Hydrogen-rich saline may protect against LPS-induced EMT and pulmonary fibrosis through suppressing oxidative stress.

Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

Cardioprotective Effect of Hydrogen-rich Saline on Isoproterenol-induced Myocardial Infarction in Rats.

BACKGROUND: Infusion with hydrogen gas-saturated saline has recently been reported to exert antioxidant and anti-inflammatory activity that may protect against organ damage induced by oxidative stress. Therefore because oxidative stress plays a significant role in the pathophysiology of myocardial infarction (MI), the aim of our study was to investigate whether hydrogen-rich saline has cardioprotective effects against isoproterenol-induced MI in rats. METHODS: An acute MI model was induced in male Wistar rats by subcutaneous injection of isoproterenol. Different doses of hydrogen-rich saline (5, 7.5, and 10 mL/kg body weight i.p.) or Vitamin C (250 mg/kg body weight i.g.) were administered to the rats. Oxidative stress indices including levels of myocardial marker enzymes, inflammatory cytokines, membrane-bound myocardial enzymes and histopathological changes were measured. RESULTS: Compared with those in isoproterenol-MI group, hydrogen-rich saline decreased malondialdehyde and 8-hydroxy-desoxyguanosine concentrations, enhanced superoxide dismutase and Na(+)-K(+)-ATPase activity, lowered Ca(2+)-ATPase activity and decreased interleukin-6 and tumour necrosis factor-α levels in the serum and/or cardiac tissue of rats. Hydrogen-rich saline pretreatment also diminished infarct size, improved left heart function, and ameliorated pathological changes of the left heart. CONCLUSION: From these results, hydrogen-rich saline exerts cardiovascular protective effects against isoproterenol-induced MI at least in part via interactions which evoke antioxidant and anti-inflammatory activities.

Nuclear factor-κB/Bcl-XL pathway is involved in the protective effect of hydrogen-rich saline on the brain following experimental subarachnoid hemorrhage in rabbits.

Early brain injury (EBI), a significant contributor to poor outcome after subarachnoid hemorrhage (SAH), is intimately associated with neuronal apoptosis. Recently, the protective role of hydrogen (H2 ) in the brain has been widely studied, but the underlying mechanism remains elusive. Numerous studies have shown nuclear factor-κB (NF-κB) as a crucial survival pathway in neurons. Here we investigated the role of H2 in EBI following SAH, focusing on the NF-κB pathway. A double blood injection model was used to produce experimental SAH, and H2 -rich saline was injected intraperitoneally. NF-κB activity within the occipital cortex was measured. Immunofluorescence was performed to demonstrate the activation of NF-κB; Bcl-xL and cleaved caspase-3 were determined via Western blot. Gene expression of Bcl-xL was detected by real-time PCR, and TUNEL and Nissl staining were performed to illustrate brain injury in the occipital cortex. SAH induced a significant increase of cleaved caspase-3. Correspondingly, TUNEL staining demonstrated obvious neuronal apoptosis following SAH. In contrast, H2 treatment markedly increased NF-κB activity and the expression of Bcl-xL and decreased the level of cleaved caspase-3. Additionally, H2 treatment significantly reduced post-SAH neuronal apoptosis. The current study shows that H2 treatment alleviates EBI in the rabbits following SAH and that NF-κB/Bcl-xL pathway is involved in the protective role of H2 .

Intrathecal transplantation of bone marrow stromal cells attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury in rabbits.

OBJECTIVE: Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the spinal cord. The blood-spinal cord barrier is critical to maintain spinal cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-spinal cord barrier after spinal cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury. METHODS: This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 10(8) in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-spinal cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. RESULTS: Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits (P < .01) and attenuated EB extravasation at 4 hours (5.41 ± 0.40 vs 7.94 ± 0.36 µg/g; P < .01) and 24 hours (9.03 ± 0.44 vs 15.77 ± 0.89 µg/g; P < .01) after spinal cord ischemia-reperfusion injury. In addition, bone marrow stromal cells treatment suppressed spinal cord ischemia-reperfusion injury-induced decreases in occludin (P < .01). Finally, bone marrow stromal cells reduced the excessive expression of MMP-9 and TNF-α (P < .01). CONCLUSIONS: Pre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-spinal cord barrier integrity after spinal cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating spinal cord injury after aortic occlusion. CLINICAL RELEVANCE: Clinical thoracoabdominal aorta surgery may trigger spinal cord ischemia-reperfusion injury, resulting in paraplegia as well as bladder, bowel, and sexual dysfunction. Transplantation of bone marrow stromal cells has attracted increasing attention in the field of nervous system protection, but its mechanisms have not been elucidated completely. The blood-spinal cord barrier plays a crucial role to maintain normal spinal cord function. This study suggested that intrathecal transplantation of bone marrow stromal cells stabilized blood-spinal cord barrier integrity through inhibiting the upregulation of matrix metalloproteinase-9 and tumor necrosis factor-a and ameliorated spinal cord ischemia-reperfusion injury. This may provide a novel train of thought to enhance the protective effects of bone marrow stromal cells on spinal cord injury.

Effects of hydrogen-rich saline treatment on polymicrobial sepsis.

BACKGROUND: Hydrogen has been reported to selectively reduce hydroxyl radicals and peroxynitrite anion in many pathologic processes. This study aimed to test the hypothesis that hydrogen-rich saline (HRS) may ameliorate organ dysfunction in a rat model of polymicrobial sepsis. METHODS: Sepsis was induced in male Sprague-Dawley rats by cecal ligation and puncture (CLP). Twenty-four rats were equally assigned to Sham group, CLP group, and CLP + HRS group (n = 8). At 0, 6, and 18 h after CLP or sham operation, rats received an intraperitoneal injection of HRS (5 mL/kg) or the same volume of normal saline. Malondialdehyde, superoxide dismutase activities, inflammatory mediators, pulmonary nitric oxide, myeloperoxidase activities, wet-to-dry weight ratio, histologic scores, apoptotic analysis, alanine aminotransferase, creatinine, and blood urea nitrogen were assessed at 24 h after operation. The 7-d survival rate was also recorded. RESULTS: HRS administration significantly reduced the serum high-mobility group box, alanine aminotransferase, creatinine, and blood urea nitrogen levels; the pulmonary interleukin 6, high-mobility group box, nitric oxide, and malondialdehyde levels; and the wet-to-dry weight ratio, total histologic scores, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, whereas it increased the superoxide dismutase activities 24 h after CLP when compared with the CLP group. However, there was no significant difference in survival rate between the CLP + HRS and CLP groups. CONCLUSIONS: HRS has potential protective effects against sepsis by decreasing proinflammatory responses, oxidative stress, and apoptosis in a rat model of polymicrobial sepsis.

[Label-free monitoring 5-FU induced SW 620 cells apoptosis using FTIR microspectroscopy].

The aim of the present study was to evaluate Fourier transform infrared spectroscopy (FTIR) monitoring of biochemical changes in apoptosis cells. Different concentrations of 5-fluorouracil (5-FU) treated colon cancer cell lines SW620 were used to determine the optimum concentration of 5-FU IC50 by means of MTT assay. Cell starvation and 5-Fu synergistic cell cycle arrest was in G1 and S phase. FTIR combined with flow cytometry was applied to analysis of SW 620 cells and SW620 cells treated with 5-FU for 12h, 24h (early apoptosis) and 48 h (late apoptosis) respectively. The peak position and the intensity of all bands were measured and comparison was made between the SW620 and apoptotic SW620 cells. Apoptosis cells have following characteristics compared with SW620 cells (1) The band at 1 740 cm-1 is an C=O stretching vibration. Changes in these bands can reflect lipid changes, and relative peak intensity ratio 11740/11460 significantly increased (p<0. 05), indicating that the relative contents of lipid in apoptosis cells increased. (2) The band at the 1 410 cm-1 peak represents that C-H stretching related was increased to amino acid residues and shifted to higher wave numbers compared to other groups. I1410o/I 460 at early and late death phase was significantly increased, which suggests that the relative contents of amino acid residues in apoptosis cells increased (p <0. 05). New vibrational bands at 1 120 cm-1 appeared at 24 h and increased at 48 h compared with other groups. The 1 120 cm-1 absorption band is mainly due to ser, serine and threonine C-O(H) stretching vibration, and I1120/I 1460 significantly increased (p<0. 05), indicating that the relative quantity of amino acid residues in apoptosis cells increased due to that DNA unwinds the double helix. (3) 1 240 cm-1 is mainly due to the asymmetric stretching modes of phosphodiester groups shifting to higher wave number, illustrating that nucleic acid conformation was changed in apoptosis cells. (4) The band 1 040 cm-1 associated with polysaccharide appeared at 24 and 48 h, meanwhile shifted to higher wave number, suggesting that polysaccharide decreased in late apoptotic cells, and I 1040/I1400 increased at late stage apoptosis, indicating that the relative content of polysaccharide in apoptosis cells increased. The authors' results suggest that FTIR applied to monitoring SW620 cells apoptosis may be as a potential diagnostic tool for cancer chemotherapy monitoring.

Sciatic hernia led to strangulated ileum and ipsilateral ovary: A case report and review of literature.

Sciatic hernia is one of the rarely pelvic floor hernias. We report a 45-year-old woman who presented with acute crampy pain of hypogastrium which radiated down the back of the left thigh and found a mass in her left buttock area which is about fist size with local pain, so she had to force to bow position when walking. She was also associated with definite gastro-intestinal symptoms. Computed tomography (CT) of the pelvis and abdomen demonstrated the herniation of an ileal loop through the sciatic foramen on the left side. The diagnosis and management of this case are herein described and previous publications on sciatic hernias are reviewed.

Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits.

BACKGROUND: Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits. RESULTS: The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH+saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious. CONCLUSION: The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.

Identification of colitis and cancer in colon biopsies by Fourier Transform Infrared spectroscopy and chemometrics.

Cancer is a disease that does great harms to the health of human beings. FT-IR spectroscopy could identify variability at the molecular level in biological specimens. It is a rapid and noninvasive method, which could be used intraoperatively to modify surgical procedures. The aim of this paper is to identify and separate cancer from colitis in endoscopic colon biopsies through the use of FT-IR spectroscopy. A total of 88 endoscopic colon samples, including 41 cases of colitis and 47 cases of colon cancer, were obtained. Specimens were placed on an ATR accessory linked to FT-IR spectrometer with a MCT detector for greater stability and sensitivity. Later, specimens were sent for the histological examination as the reference in the spectral analysis. 41 colitis and 47 cancer specimens were compared. Spectra preprocessed with smoothing and normalization were used for discrimination analysis. PCA was processed to simplify the spectrum data set. Naive Bayes classifier model was constructed for diagnostic classification. Leave-one-out cross-validation method was utilized to assess the discrimination results. The sensitivity of FT-IR detection for cancer achieves 97.6%. The results showed that colon cancer could be distinguished from colitis with high accuracy using FT-IR spectroscopy and chemometrics.

Comparison of the performance of MS enteroscope series and Japanese double- and single-balloon enteroscopes.

BACKGROUND: Small intestine disease endangers human health and is not easy to locate and diagnose. AIM: To observe the effect of the MS series of small intestine endoscopes on the gastrointestinal tract, the changes in serum gastrin levels and intestinal tissue, and the time required for the examination. METHODS: In vivo experiments in 20 Living pigs were conducted, Bowel preparation was routinely performed, Intravenous anesthesia with propofol and ketamine was applied, the condition of the small intestine was observed and the detection time of the MS series of small intestine endoscopes were recorded, The changes in intestinal tissue using the MS series of small intestine endoscopes observed and compared before and after the examination, Venous blood (3-5 mL) from pigs was collected before and after the experiment; changes in intestinal tissue after use of the MS series of small intestine endoscopes observed after examination. After completion of each type of small intestine endoscope experiment, the pigs were allowed to rest and the next type of small intestine endoscope experiment was performed after 15 days of normal feeding. The detection time data of the single-balloon small intestine endoscope and double-balloon small intestine endoscope were collected from four hospitals. RESULTS: One case of Ascarislumbricoides, one of suspected Crohn's disease, one small intestinal diverticulum and one anesthesia accident were observed in pigs. The small intestine showed no differences in the MS series of small intestine endoscopes and there were no differences in serum gastrin between the groups (P > 0.05). The time required for inspection was recorded, and the overall detection time for the Japanese small intestine endoscopes was approximately 1.68 ± 0.16 h. CONCLUSION: Intestinal ascariasis is a common disease in pigs. Some pigs have abnormal intestinal variation. After continuous upgrade and improvement, the MS-3 and MS-4 small intestine endoscope appear superior in terms of detection time.

Erratum: Vitexin Inhibits Gastric Cancer Growth and Metastasis through HMGB1-mediated Inactivation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

This corrects the article on p. 439 in vol. 21, PMID: 35079445.

The ECSIT Mediated Toll3-Dorsal-ALFs Pathway Inhibits Bacterial Amplification in Kuruma Shrimp.

The Toll signaling pathway plays an important role in animal innate immunity. However, its activation and signal transmission greatly differ across species and need to be investigated. Shrimp farming is a worldwide economic activity affected by bacterial disease from the 1990s, which promoted research on shrimp immunity. In this study, we first proved that, among the three identified Toll receptors in Marsupenaeus japonicus kuruma shrimp, Toll 3 plays a pivotal role in initiating the antibacterial response in vivo, especially upon anti-Staphylococcus aureus infection. Further research showed that this result was due to the activation of the Dorsal transcription factor, which induced the expression of two anti-lipopolysaccharide factors (Alfs). Moreover, the evolutionarily conserved signaling intermediate in Toll pathways, ECSIT, was proved to be needed for signal transmission from Toll 3 to Dorsal and the expression of anti-lipopolysaccharide factors. Finally, the mortality assay showed that a Toll3-ECSIT-Dorsal-Alf axis was functional in the anti-S.aureus immunity of M. japonicus shrimp. The results provide new insights into the function and signal transduction of the Toll pathway in aquatic species and offer basic knowledge for shrimp disease control and genetic breeding.

Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity.

OBJECTIVE: We investigated the feasibility and efficacy of hydrogen-rich saline therapy on delayed neurologic sequelae in a rat model of severe acute carbon monoxide (CO) poisoning. DESIGN: Controlled animal study. SETTING: University research laboratory for Diving Medicine. SUBJECTS: Sprague-Dawley rats weighing 250 ± 20 g. INTERVENTIONS: The rats were exposed to 1000 ppm CO in air for 40 min and then to 3000 ppm for another 20 min until they lost consciousness. Rats were intraperitoneal injected with hydrogen-rich saline or normal saline (10 mL/kg) for six times after resuscitation at 0, 12, 24, 36, 48, and 60 hrs, respectively. The rats without CO poisoning were used as normal controls. MEASUREMENTS AND MAIN RESULTS: Brain tissue inflammation, cell death, and cognitive dysfunction were observed at one week after CO poisoning. Hydrogen-rich saline treatment significantly reduced the level of degraded myelin basic protein, decreased the expression of ionized calcium-binding adapter molecule 1, Iba1, a microglial marker, reduced DNA oxidation, and suppressed proinflammatory cytokine interleukin-1ß, interleukin-6, and tumor necrosis factor-α in the cortex and hippocampal tissues when compared with those in normal saline-treated rats. These histologic and biological improvements were accompanied with an improvement in the Morris water maze test. CONCLUSIONS: This observation demonstrated that hydrogen-rich saline peritoneal injection improves histologic and functional assessment in a rat model of CO encephalopathy. Hydrogen saline has potentials as a novel and alternative therapy for severely CO-poisoned patients with delayed neurologic sequelae. The therapeutic effects of hydrogen-rich saline may be related to antioxidant and anti-inflammatory actions.

Protective effects of hydrogen-rich saline on monocrotaline-induced pulmonary hypertension in a rat model.

BACKGROUND: Hydrogen-rich saline has been reported to have antioxidant and anti-inflammatory effects and effectively protect against organ damage. Oxidative stress and inflammation contribute to the pathogenesis and/or development of pulmonary hypertension. In this study, we investigated the effects of hydrogen-rich saline on the prevention of pulmonary hypertension induced by monocrotaline in a rat model. METHODS: In male Sprague-Dawley rats, pulmonary hypertension was induced by subcutaneous administration of monocrotaline at a concentration of 6 mg/100 g body weight. Hydrogen-rich saline (5 ml/kg) or saline was administered intraperitoneally once daily for 2 or 3 weeks. Severity of pulmonary hypertension was assessed by hemodynamic index and histologic analysis. Malondialdehyde and 8-hydroxy-desoxyguanosine level, and superoxide dismutase activity were measured in the lung tissue and serum. Levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6) in serum were determined with enzyme-linked immunosorbent assay. RESULTS: Hydrogen-rich saline treatment improved hemodynamics and reversed right ventricular hypertrophy. It also decreased malondialdehyde and 8-hydroxy-desoxyguanosine levels, and increased superoxide dismutase activity in the lung tissue and serum, accompanied by a decrease in pro-inflammatory cytokines. CONCLUSIONS: These results suggest that hydrogen-rich saline ameliorates the progression of pulmonary hypertension induced by monocrotaline in rats, which may be associated with its antioxidant and anti-inflammatory effects.

The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats.

BACKGROUND: Hydrogen has been considered as a novel antioxidant that prevents injuries resulted from ischemia-reperfusion (I/R) injury in various tissues. The study was designed to determine the effect of hydrogen-rich saline on the smooth muscle contractile response to KCl, and on epithelial proliferation and apoptosis of intestine subjected to I/R. METHODS: Intestinal I/R injury was induced in Sprague-Dawley rats using bulldog clamps in superior mesenteric artery by 45 min ischemia followed by 1 h reperfusion. Rats were divided randomly into four groups: sham-operated, I/R, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment groups. Hydrogen-rich saline (>0.6 mM, 6 mL/kg) or saline (6 mL/kg) was administered, respectively, via tail vein 30 min prior to reperfusion. Following reperfusion, segments of terminal jejunum were rapidly taken and transferred into isolated organ bath and responses to KCl were recorded. Samples of terminal jejunum were also taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in intestinal epithelium was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression and distribution of proliferating cell nuclear antigen (PCNA) were detected with immunohistochemistry. RESULTS: Hydrogen-rich saline treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis, and promoting enterocytes proliferation. Moreover, Hydrogen-rich saline treatment significantly limited the neutrophil infiltration, lipid oxidation, and ameliorated the decreased contractility response to KCl in the intestine subjected to I/R. CONCLUSIONS: These results suggest that hydrogen treatment has a protective effect against intestinal contractile dysfunction and damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis, and to promote epithelial cell proliferation.

Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats.

BACKGROUND: Recently it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals (·OH) and peroxynitrite anion (ONOO-) in vitro and exert therapeutic antioxidant activity in many diseases. This study was designed to investigate the effect of hydrogen-rich saline on renal ischemia/reperfusion (I/R) injury in rats. METHODS: A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. Physiologic saline, hydrogen-rich saline, or nitrogen-rich saline (8 mL/kg) were administered intraperitoneally at 5 min before reperfusion, respectively. RESULTS: After I/R injury, serum blood urea nitrogen (BUN), creatinine (Cr), tissue malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OhdG), TNF-α, IL-1ß, IL-6 levels, and myeloperoxidase (MPO) activity were all increased significantly, while tissue superoxide dismutase (SOD) and catalase (CAT) activities were all decreased significantly. Hydrogen-rich saline reversed these changes and relieved morphological renal injury and I/R-induced apoptosis, while no significant changes were observed in the nitrogen-rich saline-treated group compared with physiologic saline-treated group. CONCLUSIONS: Hydrogen-rich saline is able to attenuate the renal I/R injury, which is possibly by reduction of oxidative stress and inflammation.

Hydrogen resuscitation, a new cytoprotective approach.

1. Hydrogen is a colourless, odourless, tasteless and flammable gas. Hydrogen is considered a physiologically inert gas and is often used in deep sea diving medicine. In mammals, endogenous hydrogen is produced as a result of the fermentation of non-digestible carbohydrates by intestinal bacteria and it is absorbed into the systemic circulation. 2. Recent evidence indicates that hydrogen is a potent anti-oxidative, anti-apoptotic and anti-inflammatory agent and so may have potential medical application. The present review evaluates the concept of 'hydrogen resuscitation', based on knowledge that hydrogen treatment effectively protects cells, tissues and organs against oxidative injury and helps them recover from dysfunction. 3. Hydrogen therapy can be delivered by inhalation, the administration of hydrogen-enriched fluid or by approaches that affect endogenous hydrogen production. 4. Studies have shown that hydrogen resuscitation has cytoprotective effects in different cell types and disease models, including ischaemia-reperfusion injury, inflammation, toxicity, trauma and metabolic disease. The underlying mechanism may be the selective elimination of hydroxyl radicals, although other mechanisms may also be involved (e.g. hydrogen functioning as a gaseous signalling molecule). 5. Hydrogen resuscitation may have several potential advantages over current pharmacological therapies for oxidative injuries. However, more work is needed to identify the precise mechanism underlying the actions of hydrogen and to validate its therapeutic potential in the clinical setting.