Hydrogen exerts neuroprotective effects by inhibiting oxidative stress in experimental diabetic peripheral neuropathy rats.

Diabetic peripheral neuropathy (DPN) is a complex disorder caused by long-standing diabetes. Oxidative stress was considered the critical creed in this DPN pathophysiology. Hydrogen has antioxidative effects on diabetes mellitus and related complications. However, there is still no concern on the beneficial effects of hydrogen in DPN. This paper aimed to evaluate the effects of exogenous hydrogen to reduce the severity of DPN in streptozotocin-induced diabetic rats. Compared with hydrogen-rich saline treatment, hydrogen inhalation significantly reduced blood glucose levels in diabetic rats in the 4th and 8th weeks. With regard to nerve function, hydrogen administration significantly attenuated the decrease in the velocity of motor nerve conduction in diabetic animals. In addition, hydrogen significantly attenuated oxidative stress by reducing the level of malondialdehyde, reactive oxygen species, and 8-hydroxy-2-deoxyguanosine and meaningfully enhanced the antioxidant capability by partially restoring the activities of superoxide dismutase. Further studies showed that hydrogen significantly upregulated the expression of nuclear factor erythroid-2-related factor 2 and downstream proteins such as catalase and hemeoxygenase-1 in the nerves of diabetic animals. Our paper showed that hydrogen exerts significant protective effects in DPN by downregulating oxidative stress via the pathway of nuclear factor erythroid-2-related factor 2, which suggests its potential value in clinical applications.

Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.

Quantification of lumbar vertebral fat deposition: Correlation with menopausal status, non-alcoholic fatty liver disease and subcutaneous adipose tissue.

Purpose: To assess abdominal fat deposition and lumbar vertebra with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) and investigate their correlation with menopausal status. Materials and Methods: Two hundred forty women who underwent routine abdominal MRI and IDEAL-IQ between January 2016 and April 2021 were divided into two cohorts (first cohort: 120 pre- or postmenopausal women with severe fatty livers or without fatty livers; second cohort: 120 pre- or postmenopausal women who were obese or normal weight). The fat fraction (FF) values of the liver (FFliver) and lumbar vertebra (FFlumbar) in the first group and the FF values of subcutaneous adipose tissue (SAT) (FFSAT) and FFlumbar in the second group were measured and compared using IDEAL-IQ. Results: Two hundred forty women were evaluated. FFlumbar was significantly higher in both pre- and postmenopausal women with severe fatty liver than in patients without fatty livers (premenopausal women: p < 0.001, postmenopausal women: p < 0.001). No significant difference in the FFlumbar was observed between obese patients and normal-weight patients among pre- and postmenopausal women (premenopausal women: p = 0.113, postmenopausal women: p = 0.092). Significantly greater lumbar fat deposition was observed in postmenopausal women than in premenopausal women with or without fatty liver and obesity (p < 0.001 for each group). A high correlation was detected between FFliver and FFlumbar in women with severe fatty liver (premenopausal women: r=0.76, p<0.01; postmenopausal women: r=0.82, p<0.01). Conclusion: Fat deposition in the vertebral marrow was significantly associated with liver fat deposition in postmenopausal women.

Metal-Organic Frameworks Featuring 18-Connected Nonanuclear Rare-Earth Oxygen Clusters and Cavities for Efficient C2H2/CO2 Separation.

Two rare-earth (RE) metal-organic frameworks (MOFs) formulated as {(Me2NH2)2[RE9(µ3-OH)8(µ2-OH)3(DCPB)6(H2O)3]}n (RE = Y3+ and Tb3+; termed JXNU-10) built from a triangular 3,5-di(4'-carboxylphenyl)benzoic acid (DCPB3-) ligand are presented. JXNU-10 features the rarely observed 18-connected nonanuclear [RE9(µ3-OH)8(µ2-OH)3] clusters, one-dimensional-nanosized tubular channels, and trigonal-bipyramidal cavities. The presence of the high-nuclear RE-oxo clusters and the robust coordination bonds between the highly charged RE ions and the hard base of the carboxylate/hydroxyl oxygen atoms yielded the water-resistant JXNU-10 materials. JXNU-10 exhibits highly selective sorption of C2H2 over CO2 and highly efficient separation of a C2H2 and CO2 mixture. The carboxylate oxygen atoms and the rich π systems of the organic ligands on the pore walls are the desirable binding sites for a C2H2 molecule with acidic hydrogen atoms and an alkyne group, facilitating the excellent efficiency of JXNU-10 for C2H2/CO2 separation demonstrated by breakthrough experiments.

Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells.

Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor Î³ (PPARγ)/liver X receptor α (LXRα) in THP­1 macrophage-derived foam cells. THP­1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP­1 macrophage-derived foam cells.

Characteristics of exogenous carbon monoxide deliveries.

Carbon monoxide (CO) has long been considered an environmental pollutant and a poison. Exogenous exposure to amounts of CO beyond the physiologic level of the body can result in a protective or adaptive response. However, as a gasotransmitter, endogenous CO is important for multiple physiologic functions. To date, at least seven distinct methods of delivering CO have been utilized in animal and clinical studies. In this mini-review, we summarize the exogenous CO delivery methods and compare their advantages and disadvantages.

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.

Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells.

The hepatocyte growth factor (HGF)/c-Met signaling pathway results in cancer cell scattering and invasion, and has been reported to participate in several types of cancer, including prostate and colorectal cancer. The downstream phosphorylation cascade of HGF, particularly the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT signaling pathway, regulates epithelial-mesenchymal transition (EMT). However, the mechanism by which these signaling pathways govern EMT, and whether certain kinases are able to respond to specific EMT effectors, remains to be elucidated. In the present study, an increase in the levels of vimentin, rather than co-regulation of certain EMT marker proteins, was observed in response to HGF-induced EMT in DU145 prostate cancer cells. In addition, it was observed that curcumin abrogated HGF-induced DU145 cell scattering and invasion. Furthermore, curcumin was able to effectively inhibit the HGF-induced increase in the levels of vimentin by downregulating the expression of phosphorylated c-Met, extracellular signal-regulated kinase and Snail. In conclusion, the results of the present study demonstrated that curcumin was able to reverse HGF-induced EMT, possibly by inhibiting c-Met expression in DU145 prostate cancer cells.

Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning.

OBJECTIVE: Delayed neuropsychological sequelae (DNS) are the most common and serious effects of severe carbon monoxide (CO) poisoning, occurring in approximately half of all CO poisoning cases. Growing evidence suggests that oxidative stress and secondary reactions in delayed brain injury are crucial to CO toxicity, similar to ischaemia-reperfusion injury. Exogenous methane plays a protective role in ischaemia-reperfusion injury by affecting key events through anti-oxidant, anti-inflammatory, and anti-apoptosis actions. Our study aimed to explore the potential of exogenous methane to relieve the severity of DNS. METHODS: Thirty-six male Sprague-Dawley (SD) rats were divided into three groups of normal-, CO- and CO plus methane-treated rats. The rats in the latter two groups were exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO exposure, saline or methane saline (10 ml/kg) was intraperitoneally administered to rats in the CO group or the CO plus methane group, respectively. On the ninth day after CO exposure, Morris water maze testing, histological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and immunohistochemical labelling were performed on 6 rats in each group. The remaining 6 rats in each group were used to detect oxidative damage markers, inflammatory cytokines and apoptosis proteins. RESULTS: Methane significantly improved CO-impaired pathological characteristics as well as learning and memory performance. In addition, methane significantly increased the superoxide dismutase (SOD) activity, lowered the CO-increased level of malondialdehyde (MDA) 3-nitrotyrosine (3-NT) and 8-hydroxy-2-deoxyguanosine (8-OHdG), inhibited levels of tumour necrosis factor-α (TNF-α), interleukin 1-ß (IL1-ß) and caspase-3 in the rat cerebral cortex and hippocampus but had no effect on IL-6 levels. CONCLUSION: The hippocampus was the main target of CO-induced alterations in the rat brain compared to the cerebral cortex. Methane treatment protected the rat brain from the harmful effects induced by CO exposure and improved the outcome of DNS through anti-oxidant, anti-inflammatory and anti-apoptosis activities.

Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and accumulating evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. The aim of this work was to investigate the effect of treatment with hydrogen molecule on the development of disease in mutant SOD1 G93A transgenic mouse model of ALS. Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.

Curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through AMPK-SIRT1-LXRα signaling in THP-1 macrophage-derived foam cells.

Curcumin, a traditional Chinese derivative from the rhizomes of Curcuma longa, is beneficial to health by modulating lipid metabolism and suppressing atherogenesis. A key part of atherosclerosis is the failure of macrophages to restore their cellular cholesterol homeostasis and the formation of foam cells. In this study, results showed that curcumin dramatically increased the expression of ATP-binding cassette transporter 1 (ABCA1), promoted cholesterol efflux from THP-1 macrophage-derived foam cells, and reduced cellular cholesterol levels. Curcumin activated AMP-activated protein kinase (AMPK) and SIRT1, and then activated LXRα in THP-1 macrophage-derived foam cells. Inhibiting AMPK/SIRT1 activity by its specific inhibitor or by small interfering RNA could inhibit LXRα activation and abolish curcumin-induced ABCA1 expression and cholesterol efflux. Thus, curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through activating AMPK-SIRT1-LXRα signaling in THP-1 macrophage-derived foam cells. This study describes a possible mechanism for understanding the antiatherogenic effects of curcumin on attenuating the progression of atherosclerosis.

Diffusion tensor imaging of symptomatic nerve roots in patients with cervical disc herniation.

RATIONALE AND OBJECTIVES: Cervical disc degeneration can result in nerve root compression and severe symptoms that significantly impair the patient's quality of life. The purpose of this study is to investigate multiple diffusion metrics changes in the diffusion tensor imaging (DTI) of cervical nerve roots and their relationship with the clinical severity of patients with cervical disc herniation. MATERIALS AND METHODS: High directional DTI of the cervical nerve roots was performed in 18 symptomatic patients and 10 healthy volunteers with a 3.0-T magnetic resonance system after a routine cervical disc scanning. The fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the DTI data and compared between the affected and unaffected sides in the same patient and between healthy volunteers and symptomatic patients. The correlation between the side-to-side diffusion metric differences and the clinical International Standards for Neurological Classification of Spinal Cord Injury scores was analyzed. RESULTS: C5-C8 nerve roots were clearly delineated with DTI. The FA, MD, AD, and RD of compressed nerve roots were 0.31 ± 0.091, 2.06 ± 0.536, 2.69 ± 0.657, and 1.75 ± 0.510 mm(2)/s, respectively. Compared to the unaffected side or healthy volunteers, the nerve roots of the affected side showed decreased FA (P < .022) and increased MD (P < .035), AD (P < .047), and RD (P < .012). The clinical International Standards for Neurological Classification of Spinal Cord Injury scores of the patients were negatively correlated with MD (r = -0.57, P = .002), AD (r = -0.451, P = .021), and RD (r = -0.564, P = .003) but not with FA (r = 0.004, P = .984). CONCLUSIONS: DTI can potentially be used to assess microstructural abnormalities in the cervical nerve roots in patients with disc herniation.

Effects of simulated heliox diving at high altitudes on blood cells, liver functions and renal functions.

The aim of the present study was to examine the effects of simulated heliox diving at high altitudes on divers' blood cells, liver functions and renal functions. In this experiment, four divers lived for nine consecutive days in a dual-function high-low pressure chamber, which simulated air pressure at an altitude of 3,000 meters and at a 30-meter depth; an altitude of 4,000 meters and 30-meter depth; and at an altitude of 5,200 meters and 30 meters and 50 meters in depth. Total time underwater was 60 minutes. The subjects breathed heliox (with oxygen at 40% and helium at 60%) during the simulated 30-meter dive from zero altitude to 30 meters and while remaining underwater; they breathed air while ascending from 30 meters to 18. They breathed heliox (with oxygen at 26.7% and helium at 73.3%) in the simulated dive from zero altitude to 50 meters underwater, in remaining underwater and in ascending from 50 meters to 29; air while ascending from 29 meters to 18. Pure oxygen was breathed while ascending from 18 meters to the surface; then air. Results indicated: (1) the correlating indices of routine blood, liver and renal functions, and urine routine were all within normal reference ranges; and (2) the indices tested at other periods of time were not significantly different (p > 0.05) from the results at zero-meter level and 3,000-meter level. The study suggests that the heliox diving processes at different high altitudes simulated in this experiment have no significant impact upon divers' blood routine, liver functions and renal functions.

Hyperbaric oxygen therapy in rats attenuates ischemia-reperfusion testicular injury through blockade of oxidative stress, suppression of inflammation, and reduction of nitric oxide formation.

OBJECTIVE: To evaluate the therapeutic utility of hyperbaric oxygen (HBO) therapy on testicular ischemia/reperfusion (I/R) injury and elucidate the underlying molecular mechanism, we tested whether HBO therapy provided rescue of the testes after torsion in rats. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: control group, control plus HBO therapy, I/R group, and I/R plus HBO therapy. The I/R model was induced by torsion of the right testis. RESULTS: I/R in the testis resulted in disrupted seminiferous tubules, germ cell-specific apoptosis, followed by a marked reduction in testis weight and daily sperm production. HBO therapy preserved seminiferous tubules, suppressed apoptosis, and prevented testicular atrophy in I/R testes. HBO therapy abated oxidative stress in I/R testes, marked by reduced malondialdehyde formation, enhanced activities of superoxide dismutase and heme oxygenase 1 (HO-1), and decreased activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase. HBO therapy resulted in a reduction of myeloperoxidase (MPO) activity in I/R testes, a marker of neutrophil recruitment. HBO therapy suppressed inflammation in I/R testes, marked by reduced messenger RNA (mRNA) levels of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), and CD44. Furthermore, HBO therapy suppressed the activation of nuclear factor kappa B (NFκB), p38, and c-JUN-N-terminal kinase (JNK) signaling pathways in I/R testes. In addition, HBO therapy reduced nitric oxide formation in I/R testes through suppression of inducible nitric oxide synthase and dimethylarginine dimethylaminohydrolase. CONCLUSION: HBO therapy in rats attenuated I/R-induced testicular injury, possibly through abating oxidative stress, suppressing inflammation, and reducing nitric oxide formation.

Imaging characteristics of abdominal tumor in association with paraneoplastic pemphigus.

The purpose of this study was to report the imaging manifestations of tumor associated with PNP. Imaging features of abdominal tumor associated with PNP in 6 cases were retrospectively analyzed. Patients were given PET/CT (n = 1) or multidetector CT (n = 5) examination. Six cases of PNP were associated with hyaline-vascular type Castleman's disease. Calcification was revealed in 2 cases. One case showed heterogeneous FDG uptake on PET. Among the 5 cases receiving a dynamic enhanced CT scan, inhomogeneous marked enhancement (n = 3) or moderate enhancement (n = 2) with hypo-attenuation areas of patchy shape were presented in the arterial phase. Three cases showed persistent enhancement in equilibrium and delayed phases, and intratumoral hypo-attenuation areas which pathologically proved to be an abundance of fibrotic components which gradually disappeared. PNP is a relatively rare special type of pemphigus, with distinctive clinical and pathological manifestations. Imaging examination plays important role in the detection and qualitative diagnosis of abdominal tumors associated with PNP.

[Diagnostic value of multi-slice spiral CT three dimensional reconstruction in maxillofacial diseases].

OBJECTIVE: To evaluate the diagnostic value of multi-slice spiral CT (MSCT) three dimensional (3D) reconstruction for maxillofacial diseases. METHODS: Sixty patients with maxillofacial diseases underwent the scanning of MSCT with 3D reconstruction. Among them, 34 patients with maxillofacial fracture, 10 patients with maxillofacial tumors and tumor-like diseases, and 16 patients with congenital deformities. The MSCT scanned with slice thickness of 2 mm. The methods of 3D reconstruction included multi-planar reconstruction (MPR), shaded surface display (SSD), and volume rendering (VR). The results were compared with what was observed during operations. RESULTS: Totally 36 cases of maxillofacial fracture were shown by 2D or 3D imaging and were validated by the observations during operation. The MSCT with 3D reconstruction imaging was significantly superior to 2D axial imaging in maxillofacial fracture. Three dimensional imaging could clearly show the spacial anatomy of facial, fragment displacement, and tracing fracture lines. However, 2D imaging had better effectiveness than 3D imaging in observing deep structure and fine fracture. In maxillofacial tumors and tumor-like diseases, 3D imaging was significantly superior to 2D axial imaging in showing the tumor shape and spacial relationships between tumors and surrounding structures. Two dimensional imaging and MPR imaging were excellent to reveal internal structure and pathological changes of tumors. 2D imaging and MPR imaging also achieved better results in showing tumors extended to soft tissues. In maxillofacial congenital deformities, 3D imaging were superior than 2D imaging. CONCLUSION: 3D imaging has an important value in the diagnosis and clinical assessment of maxillofacial fracture, tumor-like diseases, and congenital deformities.