Silencing of the circ-Arhgap5 RNA protects neuronal PC12 cells against injury and depends on the miR-29a-3p/Rock1 axis.

Circular RNAs (circRNAs) are abundantly expressed in human central nervous system. Here, we explored the role of circ_Arhgap5 in cerebral ischemia/reperfusion (I/R)-induced nerve injury in PC12 cells and its associated mechanism. Cell proliferation ability was assessed by 5-Ethynyl-2'-deoxyuridine (Edu) assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry (FCM) was applied to assess cell apoptotic rate. Cell death was analyzed by lactate dehydrogenase (LDH) assay. Oxygen-glucose deprivation and reoxygenation (OGD/R) up-regulates the expression of circRNA Rho GTPase activating protein 5 (circ_Arhgap5; mmu_circ_0000377) in PC12 cells. OGD/R exposure inhibited the proliferation and induced the apoptosis of PC12 cells, and the silence of circ_Arhgap5 attenuated OGD/R-induced injury in PC12 cells. miR-29a-3p was identified as a target of circ_Arhgap5 in PC12 cells. Circ_Arhgap5 knockdown-mediated protective effects in OGD/R-induced PC12 cells were reversed by the interference of miR-29a-3p. miR-29a-3p interacted with the 3' untranslated region (3'UTR) of Rho-associated coiled-coil-containing protein kinase 1 (Rock1), and circ_Arhgap5 can positively regulate Rock1 expression by sponging miR-29a-3p in PC12 cells. miR-29a-3p overexpression protected PC12 cells against OGD/R-induced damage by down-regulating Rock1. In conclusion, circ_Arhgap5 silencing protected PC12 cells from OGD/R-induced injury through mediating miR-29a-3p/Rock1 axis.

Effects of hyperbaric oxygen on NLRP3 inflammasome activation in the brain after carbon monoxide poisoning.

Neuroinflammation plays an important role in brain damage after acute carbon monoxide poisoning (ACOP). The nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing (NLRP) 3 inflammasome triggers the activation of inflammatory caspases and maturation of interleukin (IL)-1ß and -18, and has been linked to various human autoinflammatory and autoimmune diseases. In this study we investigated the effects of hyperbaric oxygen (HBO2) on NLRP3 inflammasome activation after ACOP. Mice were randomly divided into four groups: sham group (exposure to normobaric air - i.e., 21% O2 at 1 atmosphere absolute); HBO2-only group; CO + normobaric air group; and CO + HBO2 group. Cognitive function was evaluated with the Morris water maze; myelin injury was assessed by FluoroMyelin GreenTM fluorescent myelin staining and myelin basic protein (MBP) immunostaining; and mRNA and protein levels of NLRP3 inflammasome complex proteins were measured by quantitative real-time PCR and Western blot, respectively. Additionally, serum and brain levels of IL-1ßß and -18 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were determined by enzyme-linked immunosorbent assay. It was found that HBO2 improved learning and memory, and alleviated myelin injury in mice subjected to acute CO exposure. Furthermore, HBO2 decreased NLRP3, absent in melanoma 2 (AIM2), caspase-1, and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain mRNA and protein levels, and reduced brain and serum concentrations of IL-1ß and -18 and NADPH oxidase. These results indicate that HBO2 suppresses the inflammatory response after ACOP by blocking NLRP3 inflammasome activation, thereby alleviating cognitive deficits.

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.

Hyperbaric Oxygen Alleviates Secondary Brain Injury After Trauma Through Inhibition of TLR4/NF-κB Signaling Pathway.

BACKGROUND: The aim of this study was to investigate the efficacy of hyperbaric oxygen in secondary brain injury after trauma and its mechanism in a rat model. MATERIAL/METHODS: A rat model of TBI was constructed using the modified Feeney's free-fall method, and 60 SD rats were randomly divided into three groups--the sham group, the untreated traumatic brain injury (TBI) group, and the hyperbaric oxygen-treated TBI group. The neurological function of the rats was evaluated 12 and 24 hours after TBI modeling; the expression levels of TLR4, IκB, p65, and cleaved caspase-3 in the peri-trauma cortex were determined by Western blot; levels of TNF-α, IL-6, and IL-1ß were determined by ELISA; and apoptosis of the neurons was evaluated by TUNEL assay 24 hours after TBI modeling. RESULTS: Hyperbaric oxygen therapy significantly inhibited the activation of the TLR4/NF-κB signaling pathway, reduced the expression of cleaved caspase-3, TNF-α, IL-6 and IL-1ß (P<0.05), reduced apoptosis of the neurons and improved the neurological function of the rats (P<0.05). CONCLUSIONS: Hyperbaric oxygen therapy protects the neurons after traumatic injury, possibly through inhibition of the TLR4/NF-κB signaling pathway.

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.

High plasma glutamate levels are associated with poor functional outcome in acute ischemic stroke.

The aim of the present study was to investigate the relationship between acute ischemic stroke and glutamate levels and to determine the prognosis value of plasma glutamate levels to predict the functional outcome. Two hundred and forty-two patients with acute ischemic stroke and 100 sex- and age-matched controls were included in the study. Plasma glutamate levels were determined by HPLC at admission in both groups. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). The modified Rankin Scale (mRS) scores at 3 months was determined to outcomes, and unfavorable outcomes were defined as mRS at 3-6. The prognostic value analyzed by logistic regression analysis, after adjusting for the possible confounders. In the 94 patients with an unfavorable functional outcome, plasma glutamate levels were higher compared with those in patients with a favorable outcome [221(IQR, 152-321) µM; 176(IQR, 112-226) µM, respectively; P < 0.0001). In multivariate logistic regression analysis, glutamate was an independent predictor of functional outcome, with an adjusted OR of 6.99 (95 % confidence interval [CI] 2.21-21.23). Receiver operating characteristics to predict functional outcome demonstrated areas under the curve of glutamate of 0.821 (95 % CI 0.733-0.878; P < 0.0001) and combined model (glutamate and NIHSS) improved the NIHSS score alone. Plasma glutamate levels can be seen as an independent short-term prognostic marker of functional outcome in Chinese patients with acute ischemic stroke even after correcting for possible confounding factors.

Huperzine A combined with hyperbaric oxygen on the effect on cognitive function and serum hypoxia-inducible factor-1α Level in elderly patients with vascular dementia.

OBJECTIVE: To explore the clinical effect of huperzine A combined with hyperbaric oxygen on cognitive function and serum hypoxia-inducible factor-1α (HIF-1α) level in elderly patients with vascular dementia (VD). METHODS: 120 elderly VD patients admitted to our hospital from February 2018 to March 2020 were selected and divided into two groups according to the treatment method (n = 60 each). They were administered for huperzine A and huperzine A combined with hyperbaric oxygen, respectively. The comparison of disease control rate (DCR), mini-mental state examination (MMSE) score, revised hasegawa's dementia scale (HDS-R) score and serum index were conducted. RESULTS: At 2 and 4 weeks after treatment, the HDS-R and MMSE scores were reported to be higher in the observation group than those in the control group (P < 0.05), and the vascular endothelial growth factor (VEGF), anti-apoptotic factor (Livin), and HIF-1α showed a higher level of improvement as compared with the control group (P < 0.05). Moreover, the DCR in the observation group was much higher than that in the control group (P < 0.05). CONCLUSION: Huperzine A combined with hyperbaric oxygen is remarkably effective in the treatment of elderly VD patients. It can improve the serum HIF-1α level and speed up the recovery of cognitive function.

Lung adenocarcinoma and sequential antineutrophil cytoplasmic antibody-associated vasculitis: a case report.

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.

Beneficial Effect of ß-Elemene Alone and in Combination with Hyperbaric Oxygen in Traumatic Brain Injury by Inflammatory Pathway.

BACKGROUND: Present study evaluates the neuroprotective effect of ß-elemene alone and in combination with hyperbaric oxygen (HO) in traumatic brain injury (TBI). METHODOLOGY: TBI was induced by dropping a weight from a specific height. All the animals were separated in to five groups (n=20) like control group; TBI group; ß-elemene treated group which receives ß-elemene (100 mg/kg, i.p.) half an hour after the injury; HO group which receives hyperbaric oxygen therapy and ß-elemene + HO group which receives ß-elemene (100 mg/kg, i.p.) half an hour after the injury and hyperbaric oxygen therapy. Neurological function was assessed to evaluate the effect of ß-elemene in TBI rats. Thereafter level of inflammatory cytokines and expression of protein of inflammatory pathway was assessed in the brain tissues of TBI rats. In addition TUNEL assay was also done for the determination apoptosis in neuronal cells. RESULT: Data of the report reveals that ß-elemene alone and in combination with hyperbaric oxygen (HO) significantly decreases the neurological score Compared to TBI group. Moreover level of inflammatory cytokines and expression of LTR4 and casepase 3 significantly decrease and increase in the expression of IkB in ß-elemene alone and in combination with hyperbaric oxygen (HO) treated group compared to TBI group. Data of TUNEL assay also reveals that ß-elemene treated group shows significant decrease in the TUNEL positive cells and apoptosis index compared to TBI group. CONCLUSION: Thus present study concludes the neuroprotective effect of ß-elemene against TBI and it shows synergistic effect on TBI when treated with HO.

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.