Effect of magnesium on vascular calcification in chronic kidney disease patients: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of magnesium (Mg) supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, CNKI, VIP, and WanFang databases were searched from build to July 2022. Randomized controlled trials (RCT) and non-RCT related to whether Mg supplementation inhibits VC in patients with CKD were included. The literature was screened according to inclusion and exclusion criteria, and quality evaluation and data collection were performed. Meta-analysis was performed using Review Manager 5.4 software. RESULTS: 8 RCTs and 1 non-RCT studies with a total of 496 patients were eventually included. Compared to control groups, Mg supplementation increased serum Mg levels (SMD = 1.26, 95% CI: -0.70 to 1.82, p < 0.001), but it was not statistically significant in alleviating the degree of VC, increasing T50, and reducing serum phosphorus (P) levels in patients with CKD (all p > 0.05). Oral Mg reduced left (WMD=-0.06, 95% CI. -0.11 to -0.01, p = 0.03) and right (WMD=-0.07, 95% CI: -0.13 to -0.01, p = 0.02) carotid intima-media thickness (cIMT). Additionally, calcium (Ca) (SMD=-0.43, 95% CI: -0.74 to -0.11, p = 0.008) and parathyroid hormone (PTH) (SMD=-0.43, 95% CI: -0.75 to -0.11, p = 0.008) levels were reduced by increasing dialysate Mg concentration. CONCLUSIONS: Mg supplementation increased serum Mg levels and reduced Ca, PTH, and cIMT, but it did not reduce VC scores in patients with CKD. This still requires further studies with larger samples to evaluate the effect of Mg supplementation on VC.

Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway.

BACKGROUND & AIMS: Hepatic ischemia and reperfusion (I/R) injury is a major complication of liver transplantation, hepatic resection and trauma. Helium preconditioning (HPC) exerts protection against ischemic stress. We investigated potential beneficial effects of HPC on I/R-induced liver injury and investigated mechanisms underlying HPC-induced protection. METHODS: We employed a model of segmental warm hepatic I/R on BALB/c mice. Serum ALT was measured and livers were analysed by histology, RT-PCR and western blot. HPC was induced by inhalation of a 70% helium/30% oxygen mixture for three 5-min periods, interspersed with three 5-min washout periods by room air. We tested which component of HPC (the helium/air mixture inhalation, the air room gap, or the interaction between these two factors) is protective. RESULTS: We found that HPC caused a significant increase in Akt phosphorylation in hepatocytes. The HPC-induced Akt phosphorylation resulted in decreased hepatocellular injury and improved survival rate of the treated animals. PI3K inhibitors abolished HPC induced effects. HPC-induced Akt phosphorylation affected expression of its downstream molecules. The effects of HPC on the PI3K/Akt pathway were attenuated by adenosine A2A receptor blockade, but could be re-established by PTEN inhibition. We demonstrated that the interaction of helium/air breathing and air gaps is responsible for the observed effects of HPC. CONCLUSIONS: HPC may be a promising strategy leading to a decrease in I/R induced liver injury in clinical settings. Additionally, the PI3K/Akt pathway plays an essential role in the protective effects of HPC in hepatic I/R injury.

Advances in the therapy of hyperoxia-induced lung injury: findings from animal models.

Oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia at elevated partial pressure leads to inflammation and acute lung injury. The population at risk for this condition has markedly increased with the advent of efficient systems for delivery of high concentrations of oxygen in hospitals. Thus, the therapy of hyperoxia-induced lung injury has been a focus in studies of pediatrics and pulmonary medicine. In this paper, we briefly summarized the advances in the therapies of hyperoxia-induced lung injury on the basis of its pathogenesis. We hope our summary will help provide evidence for further investigation of therapeutic measures for hyperoxia-induced lung injury.

Nomogram to predict central lymph node metastasis in papillary thyroid carcinoma.

Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto's thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0-82% in the training cohort and 0-71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.

Carbon Nanoparticles for Thyroidectomy and Central Lymph Node Dissection for Thyroid Cancer.

PURPOSE: To evaluate whether the application of carbon nanoparticles (CNs) in total or near-total thyroidectomy combined with central lymph node dissection (CLND) for thyroid cancer (TC) is beneficial to lymph node dissection, parathyroid, and recurrent laryngeal nerve (RLN) protection. METHODS: Relevant literatures were systematically searched on PubMed, EMBASE, and Cochrane Library Databases until March 31, 2021. All analyses were performed using Revman Manager 5.3 software. The main results were the number of central lymph nodes, the number of central metastatic lymph nodes, accidental parathyroidectomy, postoperative hypoparathyroidism, postoperative hypocalcemia, and postoperative transient RLN paralysis. RESULTS: This meta-analysis identified 4 randomized controlled trials and 8 non-randomized controlled trials comprising 1870 patients. Compared with the control, the use of CNs was helpful to dissect more central lymph nodes (weighted mean difference [WMD]: 3.55, 95% confidence interval [CI]: 2.12-4.98, P < .00001) and central metastatic lymph nodes (WMD: 1.69, 95% CI:1.31-2.08, P < .00001), lower rate of accidental parathyroidectomy (odds ratio [OR]: .33, 95% CI: .23-.47, P < .00001), lower rate of both postoperative transient hypoparathyroidism (OR: .40, 95% CI: .31-.51, P < .00001), and transient hypocalcemia (OR: .37, 95% CI: .27-.51, P < .00001). However, there were no statistical difference between the groups for postoperative permanent hypoparathyroidism (OR: .29, 95% CI: .06-1.28, P = .10), postoperative permanent hypocalcemia (OR: .94, 95% CI: .10-9.16, P = .96), and postoperative transient RLN paralysis (OR: .66, 95% CI: .40-1.12, P = .12). CONCLUSIONS: The application of CNs in total or near-total thyroidectomy combined with CLND for TC can better dissect the central lymph nodes and protect parathyroid glands (PGs) and their function.

Comparison of bilateral axillo-breast approach robotic thyroidectomy and open thyroidectomy for papillary thyroid carcinoma.

For papillary thyroid carcinoma (PTC) surgery requiring total thyroidectomy and central lymph node dissection, it is controversial whether the bilateral axillo-breast approach robotic thyroidectomy (BABA RT) can replace the open thyroidectomy (OT). To evaluate the efficacy of two surgical approaches. Relevant literatures were searched from PubMed, EMBASE and Cochrane Library. Studies comparing two surgical approaches and meeting the inclusion criteria were selected. Compared with OT, BABA RT showed a similar incidence of postoperative complications, including recurrent laryngeal nerve palsy, hypocalcemia, hypoparathyroidism, bleeding, chyle leakage and incision infection, as well as number of retrieved central lymph nodes and postoperative total dose of radioactive iodine. However, BABA RT involved longer operative time (weighted mean difference [WMD] 72.62, 95% confidence interval [CI] 48.15-97.10, P < .00001) and higher postoperative stimulated thyroglobulin level ([WMD] 0.12, 95% [CI] 0.05-0.19, P = .0006). The efficacy of BABA RT is basically similar to OT in this meta-analysis, but the higher postoperative stimulated thyroglobulin level attracts our attention. Longer operative time requires us to shorten. Randomized clinical trials with large samples and longer follow-up data are still essential to further demonstrate the value of the BABA RT.

Triethyl-ammonium (2R,3R)-2,3-bis-(benzo-yloxy)-3-carb-oxy-propano-ate.

In the anion of the title salt, C(6)H(16)N(+)·C(18)H(13)O(8) (-), one of the carboxyl groups is deprotonated. Its O atoms are involved in inter-molecular hydrogen bonding with the carboxyl group of an adjacent anion and the amino group of an adjacent cation. The two benzoyloxy rings are oriented with respect to each other at a dihedral angle of 79.46 (6)°.

Targeting FcγRIIB by antagonistic antibody BI-1206 improves the efficacy of rituximab-based therapies in aggressive mantle cell lymphoma.

Inevitable relapses remain as the major therapeutic challenge in patients with mantle cell lymphoma (MCL) despite FDA approval of multiple targeted therapies and immunotherapies. Fc gamma receptors (FcγRs) play important roles in regulating antibody-mediated immunity. FcγRIIB, the unique immune-checkpoint inhibitory member of the FcγR family, has been implicated in immune cell desensitization and tumor cell resistance to the anti-CD20 antibody rituximab and other antibody-mediated immunotherapies; however, little is known about its expression and its immune-modulatory function in patients with aggressive MCL, especially those with multi-resistance. In this study, we found that FcγRIIB was ubiquitously expressed in both MCL cell lines and primary patient samples. FcγRIIB expression is significantly higher in CAR T-relapsed patient samples (p < 0.0001) compared to ibrutinib/rituximab-naïve, sensitive or resistant samples. Rituximab-induced CD20 internalization in JeKo-1 cells was completely blocked by concurrent treatment with BI-1206, a recombinant human monoclonal antibody targeting FcγRIIB. Combinational therapies with rituximab-ibrutinib, rituximab-venetoclax and rituximab-CHOP also induced CD20 internalization which was again effectively blocked by BI-1206. BI-1206 significantly enhanced the in vivo anti-MCL efficacy of rituximab-ibrutinib (p = 0.05) and rituximab-venetoclax (p = 0.02), but not the rituximab-CHOP combination in JeKo-1 cell line-derived xenograft models. In patient-derived xenograft (PDX) models, BI-1206, as a single agent, showed high potency (p < 0.0001, compared to vehicle control) in one aggressive PDX model that is resistant to both ibrutinib and venetoclax but sensitive to the combination of rituximab and lenalidomide (the preclinical mimetic of R2 therapy). BI-1206 sensitized the efficacy of rituximab monotherapy in a PDX model with triple resistance to rituximab, ibrutinib and CAR T-therapies (p = 0.030). Moreover, BI-1206 significantly enhanced the efficacy of the rituximab-venetoclax combination (p < 0.05), which led to long-term tumor remission in 25% of mice. Altogether, these data support that targeting this new immune-checkpoint blockade enhances the therapeutic activity of rituximab-based regimens in aggressive MCL models with multi-resistance.

Protective effect of hydrogen-rich saline on decompression sickness in rats.

INTRODUCTION: Hydrogen (H2) has been reported to be effective in the treatment of oxidative injury, which plays an important role in the process of decompression sickness (DCS). This study was designed to test whether H2-rich saline (saline saturated with molecular hydrogen) protected rats against DCS. METHODS: Models of DCS were induced in male Sprague-Dawley rats weighing 300-310 g. H2-rich (0.86 mmol x L(-1)) saline was administered intraperitoneally (10 ml x kg(-1)) at 24 h, 12 h, immediately before compression, and right after fast decompression. RESULTS: H2-rich saline significantly decreased the incidence of DCS from 67.57 to 35.14% and partially counteracted the increases in the total concentration of protein in the bronchoalveolar lavage from 0.33 +/- 0.05 to 0.14 +/- 0.01 mg x ml(-1) (mean +/- SD; P < 0.05), myeloperoxidase activity from 0.86 +/- 0.16 to 0.44 +/- 0.13 U/g, levels of malondialdehyde (MDA) from 0.80 +/- 0.10 to 0.48 +/- 0.05 nmol x mg(-1), 8-hydroxydeoxyguanosine from 253.7 +/- 9.3 to 191.2 +/- 4.8 pg x mg(-1) in the lungs, and MDA level from 1.77 +/- 0.20 to 0.87 +/- 0.23 nmol x mg(-1) in the spinal cord in rat DCS models. The histopathology results also showed that H2-rich saline ameliorated DCS injuries. DISCUSSION: It is concluded that H2-rich saline may have a protective effect against DCS, possibly due to its antioxidant action.

Combined effects of intravenous perfluorocarbon emulsion and oxygen breathing on decompression-induced spinal cord injury in rats.

The spinal cord is one of the most commonly affected sites in decompression sickness (DCS). Alternative methods have long been sought to protect against DCS spinal cord dysfunction, especially when hyperbaric treatment is unavailable. Use of perfluorocarbon (PFC) emulsion with or without oxygen breathing has shown survival benefits in DCS animal models. The effectiveness of intravenous PFC emulsion with oxygen breathing on spinal cord function was studied. Somatosensory-evoked potentials (SSEPs) and histologic examination were chosen to serve as measures. After fast decompression (203 kPa/minute) from 709 kPa (for 60 minutes), male Sprague-Dawley rats randomly received: 1) air and saline; 2) oxygen (O2) and saline; 3) O2 and PFC emulsion. The incidence and average number of abnormal SSEP waves in survival animals that received O2 and PFC emulsion were significantly reduced (P < 0.05). Foci of demyelination, necrosis and round non-staining defects in white matter regions of the spinal cord could be found in severe DCS rats. We concluded that administration of PFC emulsion combined with oxygen breathing was beneficial for DCS spinal conductive dysfunction in rats.

Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma.

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

Hyperbaric oxygen preconditioning reduces the incidence of decompression sickness in rats via nitric oxide.

Divers are at risk of decompression sickness (DCS) when the ambient pressure decrease exceeds a critical threshold. Hyperbaric oxygen (HBO2) preconditioning has been used to prevent various injuries, but the protective effect on DCS has not been well explored. To investigate the prophylactic effect of HBO2 on DCS, rats were pretreated with HBO2 (250 kPa-60 minutes) (all the pressures described here are absolute pressure) for 18 hours before a simulated air dive (700 kPa-100 minutes) with fast decompression to the surface at the rate of 200 kPa/min (n=33). During the following 30 minutes, the rats walked in a 3 m/minute rotating cage and were monitored for signs of DCS. The control rats were pretreated with normobaric air (n=30), normoxic hyperbaric nitrox (250 kPa, 8.4% O2) (n=13), or N(G)-nitro-L-arginine methyl ester (L-NAME) 30 minutes before HBO2 exposure (n=13). Nitric oxide (NO) levels were recorded immediately and 18 hours after HBO2 exposure in the brain and spinal cord. The incidence of DCS in rats pretreated with HBO2 was 30.3%, which was significantly lower than those treated with normobaric air (63.3%) (p<0.05) or hyperbaric nitrox (61.5%) (p<0.05). The onset time of DCS of the rats pretreated with HBO2 was significantly delayed compared with those treated with air (p<0.05). L-NAME nullified the HBO2 preconditioning effect. HBO2 increased NO level in the rat brain and spinal cord right after exposure; this effect was inhibited by L-NAME. Taken together, HBO2 preconditioning reduced the incidence of DCS in rats, and NO was involved in the prophylactic effect.

Protective effects of methane-rich saline on mice with allergic asthma by inhibiting inflammatory response, oxidative stress and apoptosis.

BACKGROUND: Asthma is a common cause of breathing difficulty in children and adults, and is characterized by chronic airway inflammation that is poorly controlled by available treatments. This results in severe disability and applies a huge burden to the public health system. Methane has been demonstrated to function as a therapeutic agent in many diseases. The aim of the present study was to explore the effect of methane-rich saline (MRS) on the pathophysiology of a mouse model of asthma and its underlying mechanism. METHODS: A murine model of ovalbumin (OVA)-induced allergic asthma was applied in this study. Mice were divided into three groups: a control group, an OVA group, and OVA-induced asthmatic mice treated with MRS as the third group. Lung resistance index (RI) and dynamic compliance (Cdyn) were measured to determine airway hyper-responsiveness (AHR). Haematoxylin and eosin (H&E) staining was performed and scored to show histopathological changes. Cell counts of bronchoalveolar lavage fluid (BALF) were recorded. Cytokines interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor α (TNF-α), and C-X-C motif chemokine ligand 15 (CXCL15) from BALF and serum were measured by enzyme-linked immunosorbent assay (ELISA). The oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), and 8-hydroxydeoxyguanosine (8-OHdG), were determined using commercial kits. Apoptosis was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical examination. RESULTS: MRS administration reversed the OVA-induced AHR, attenuated the pathological inflammatory infiltration, and decreased the cytokines IL-4, IL-5, IL-13, TNF-α, and CXCL15 in serum and BALF. Moreover, following MRS administration, the oxidative stress was alleviated as indicated by decreased MDA, MPO, and 8-OHdG, and elevated SOD and GSH. In addition, MRS exhibited an anti-apoptotic effect in this model, protecting epithelial cells from damage. CONCLUSIONS: Methane improves pulmonary function and decreases infiltrative inflammatory cells in the allergic asthmatic mouse model. This may be associated with its anti-inflammatory, antioxidative, and anti-apoptotic properties.

Effect of helium preconditioning on neurological decompression sickness in rats.

Decompression sickness (DCS) occurs because of an excessively rapid and extensive reduction of the ambient pressure. Bubble-induced spinal cord ischemia is generally considered as a part of neurological DCS pathogenesis. Because helium preconditioning (HPC) recently demonstrated beneficial properties against ischemic damage, we hypothesized that HPC may decrease the neurological deficits of DCS in rats. Seventy-five male Sprague-Dawley rats were divided into a non-HPC group ( n = 25) and a HPC group ( n = 25) and 25 naive animals that were euthanized for histological examination ( n = 5) or anesthetized for baseline somatosensory evoked potential (SSEP) recordings ( n = 20). To induce DCS, rats were compressed with air to a pressure of 709 kPa for 60 min and decompressed at a rate of 203 kPa/min. HPC was administered as three episodes of 79% helium-21% oxygen mixture inhalation for 5 min interspersed with 5 min of air breathing. We found that HPC resulted in significantly decreased DCS incidence and delay of DCS onset. HPC also improved animal performance on the grip test after decompression and significantly ameliorated decompression-induced decrease of platelet number. Furthermore, the incidence of abnormal SSEP waves and histological spinal lesions was significantly reduced by HPC. We conclude that HPC can decrease the occurrence of DCS and ameliorate decompression-induced neurological deficits. NEW & NOTEWORTHY Helium preconditioning ameliorates decompression-induced neurological deficits in rats. Helium breathing before air dives may prevent neurological deficit and attenuate symptoms after decompression.

Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway.

BACKGROUND AND AIMS: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism. METHODS: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R+HCH, LY294002 (PI3K inhibitor)+I/R+HCH, and LY+I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1h immediately after surgery. LY294002 was intravenously injected at 10mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A2A receptor, additional four groups were included: ZM241385 (A2A receptor antagonist)+I/R+HCH, ZM241385+I/R, bpv(HOpic) (PTEN inhibitor)+I/R, and ZM241385+bpv+I/R+HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A2A receptor in this protection. RESULTS: Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic). CONCLUSION: Our findings indicate that HCH may protect the liver against I/R injury through the A2A dependent PI3K-Akt pathway.

High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of thePI3K/Akt1 pathway.

The study investigated the role of Akt1 through the cardioprotection of high-concentration hydrogen (HCH). C57BL/6 mice were randomly divided into the following groups: sham, I/R, I/R + HCH, I/R + HCH + LY294002 (PI3K inhibitor), I/R + HCH + wortmannin (PI3K inhibitor), I/R + LY294002, and I/R + wortmannin. After 45 min of ischemia, HCH (67% H2 and 33% O2) was administered to mice during a 90-min reperfusion. To investigate the role of Akt1 in the protective effects of HCH, mice were divided into the following groups: I/R + A-674563 (Akt1 selective inhibitor), I/R + HCH + A-674563, I/R + CCT128930 (Akt2 selective inhibitor), and I/R + HCH + CCT128930. After a 4-h reperfusion, serum biochemistry, histological, western blotting, and immunohistochemical analyses were performed to evaluate the role of the PI3K-Akt1 pathway in the protection of HCH. In vitro, 75% hydrogen was administered to cardiomyocytes during 4 h of reoxygenation after 3-h hypoxia. Several analyses were performed to evaluate the role of the Akt1 in the protective effects of hydrogen. HCH resulted in the phosphorylation of Akt1 but not Akt2, and Akt1 inhibition markedly abolished HCH-induced cardioprotection. Our findings reveal that HCH may exert cardioprotective effects through a PI3K-Akt1-dependent mechanism.

Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions.

Myocardial infarction (MI) remains the most frequent cardiovascular disease with high mortality. Recently, methane has been shown protective effects on small intestinal ischemia-reperfusion injury. We hypothesized that methane-rich saline (MS) could protect the myocardium again MI via its anti-oxidative, anti-apoptotic and anti-inflammatory effects. In experiment 1, tetrazolium chloride staining and detection of myocardial enzymes and oxidative and inflammatory parameters were performed at 12h after MI to determine the optimal dose at which intraperitoneal MS exerted the best protective effects on MI. In experiment 2, rats were treated with 10 ml/kg MS. Myocyte apoptosis was detected 72 h after MI, and cardiac function and myocardial remodeling were evaluated 4 weeks after MI. Results showed different dose of MS reduced infarct area, decreased myocardial enzymes, inhibited inflammation and oxidative stress following MI. The optimal dose of MS was 10 mg/kg. Moreover, treatment with 10mg/kg MS for 3 days significantly reduced myocyte apoptosis, improved cardiac function and inhibited myocardial remodeling (reduced anterior wall thickness, attenuated myocyte hypertrophy, and decreased myocardial collagen). MS protects the myocardium of MI rats via its anti-oxidative, anti-inflammatory, anti-apoptotic and anti-remodeling activities. Thus, MS provides a novel and promising strategy for the treatment of ischemic heart diseases.

Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically.

EFFECTS OF HELIUM PRECONDITIONING ON INTESTINAL ISCHEMIA AND REPERFUSION INJURY IN RATS.

Intestinal ischemia-reperfusion (I/R) injury can occur in clinical settings such as organ transplantation, cardiopulmonary bypass and trauma. The noble gas helium attenuates I/R injury in a number of animal organs and thus may offer a strategy for reducing I/R-induced intestinal injury in clinical settings. In the present study, we used four different helium preconditioning (HPC) profiles to investigate the potential beneficial effect of HPC on I/R-induced intestinal injury. Male Sprague-Dawley rats were pretreated with three cycles of air breathing for 5 min combined with three cycles of breathing a 70% helium:30% oxygen mixture for either 2, 5, 10, or 15 min, after which they were subjected to 60-min intestinal ischemia and 60-min reperfusion. Sixty minutes after reperfusion, the intestinal tissues of the variously treated rats were analyzed using histology, immunohistochemistry, terminal dUTP nick-end labeling staining, myeloperoxidase activity assay, Western blotting, and enzyme-linked immunosorbent assay for tumor necrosis factor α and macrophage inflammatory protein 1α. Intestinal permeability was assayed by measuring fluorescein isothiocyanate-dextran release in blood samples. The results showed that the HPC profile consisting of three cycles of 10 or 15 min of helium breathing and three cycles of 5 min of air breathing reduced I/R-induced intestinal injury, cell apoptosis, and the inflammatory response. However, the 2- or 5-min helium breathing did not confer any protective effects. It seems that longer helium episodes should be used in HPC profiles designed to attenuate intestinal I/R injury.