[Retracted] LINC00665 functions as a competitive endogenous RNA to regulate AGTR1 expression by sponging miR­34a­5p in glioma.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the 'Control' data panel shown for the EdU assay experiment in Fig. 6D on p. 1209 was strikingly similar to a data panel featured in Fig. 7 that had already been submitted to the journal Cancer Management and Research by different authors at different research institutes [Chen T­J, Gao F, Yang T, Li H, Li Y, Ren H and Chen M­W: Knockdown of linc­POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer. Cancer Manag Res 12: 4379­4390, 2020]. Owing to the fact that contentious data in the above article had already been submitted for publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 1202­1212, 2021; DOI: 10.3892/or.2021.7949].

Clinical characteristics and prognosis in patients with neuronal surface antibody-mediated autoimmune encephalitis: a single-center cohort study in China.

Objective: This retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy. Methods: Clinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis. Results: Overall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0-2), and 21 patients had a poor prognosis (mRS 3-6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p<0.001). Multivariate analysis indicated that elevated neutrophil-to-lymphocyte ratio (NLR) and tumour presence were independent risk factors for poor prognosis. The regression equation of the model was logit(P)=-3.480 + 0.318 NLR+2.434 with or without tumour (with assignment =1, without assignment =0). The prediction probability generated by the regression model equation was used as the independent variable for receiver operating curve (ROC) analysis. The results showed that the area under the curve (AUC) of the prediction probability was 0.847 (95% CI, 0.733-0.961; p < 0.001). Conclusions: Different AE subtypes demonstrated different clinical symptom spectra throughout the disease stage. Anti-LGI1 encephalitis and anti-CASPR2 encephalitis were more sensitive to first-line and second-line treatments. Anti-GABABR encephalitis had the worst prognosis among the abovementioned subtypes. The regression equation constructed using NLR and tumour presence effectively predicted the poor prognosis.

Thyroid stimulating hormone correlates with triglyceride levels but is not associated with the severity of acute ischemic stroke in patients with euthyroidism: a cross-sectional study.

Background: Growing evidence suggests an association between thyroid stimulating hormone (TSH) and severity of acute ischemic stroke (AIS). However, few studies have ruled out the potential influences of abnormal thyroid hormones when assessing this association. This study aimed to investigate the association between TSH levels and the severity of AIS patients with euthyroidism, and to explore the potential mechanism of TSH on this disease by analyzing the correlation of TSH with lipid profiles. Methods: This retrospective study consisted of 345 patients with normal T3 and T4 levels admitted for first-ever cerebral ischemic stroke. Baseline data of participant were collecte. Laboratory data, including serum levels of TSH and lipid profiles were measured in our hospital's clinical laboratory on admission. Stroke severity was recorded using the National Institutes of Health Stroke Scale (NIHSS). Associations between TSH levels and disease severity were analyzed with logistic regression analysis. Correlations between TSH and lipid profiles were analyzed with Spearman's rank correlation analysis. Results: Among the 345 patients with AIS, the median age was 63 years (63±12 years), 106 patients (30.7%) were female, 237 (68.7%) patients were mild-severity and 108 (31.3%) patients were severity. Data analysis showed that higher serum TSH levels were associated with the mild severity of patients with AIS (P=0.042 in Kruskal-Wallis test, P=0.025 in logistic regression analysis, and P=0.044 in multiple logistic regression), but not in AIS patients with euthyroidism (P=0.078, P=0.337, respectively). Furthermore, TSH levels were correlated with triglycerides (TG) levels not only in total patients (r=0.135, P=0.012) but also in the patients with euthyroidism (r=0.133, P=0.018). Conclusions: TSH levels are associated with the severity of AIS patients, but not in patients with euthyroidism, predicting that stratified management of TSH may be beneficial in patients with AIS. Moreover, TSH levels are correlated with TG levels in patients with AIS.

Serum adenosine deaminase activity and acute cerebral infarction: a retrospective case-control study based on 7913 participants.

BACKGROUND: Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear. METHODS: 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity. RESULTS: Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L, p < 0.001). After Logistic regression analysis, ADA concentrations were negatively correlated with ACI (OR = 1.161, 95% CI: 1.140-1.183, p < 0.001). Smoking and alcohol consumption decreased serum ADA concentrations in patients with ACI, whereas diabetes and hypertension had the opposite effect. CONCLUSIONS: Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.

[Role of autophagy in liver injury induced by lung ischemia/ reperfusion in rats].

Objective: To investigate the liver injury induced by lung ischemia / reperfusion(LI/R) and the role of autophagy in its prevention and treatment. Methods: The lung ischemia/reperfusion injury(LI/RI) model was prepared by anesthetizing the rats, cutting the trachea for mechanical ventilation, and using an arterial clamp to close the pulmonary hilum to simulate the ischemic process, and releasing the arterial clamp after 30 min to resume perfusion for 3 h. SD rats(n=24)were randomly divided into sham operation(sham)group,ischemia/reperfusion(I/R)group,solvent(DMSO)group and autophagy inhibitor (3-MA) group, 6 rats in each group. The rats were intraperitoneally injected with medicine before operation. After the rat LI/RI model was established,the rats were killed, and the lung wet/dry weight ratio was used to evaluate the success of modeling, the venous blood was collected to measure the contents of ALT and AST, and the liver tissues were collected. Light and electron microscopes were used to observed the liver tissues and cell shapes. The protein and mRNA expression levels of autophagy related proteins were determined by Western blot and RT-qPCR to suggest autophagy levels. Results: Compared with sham group, the lung wet/dry weight ratios in other groups were elevated, and the liver tissues of other groups were damaged significantly. Serum levels of AST and ALT were increased significantly and liver tissue damage was obvious, especially in I/R group. The light microscopy showed that the arrangement of hepatic cords was disordered or broken, hepatic sinuses were dilated, and edema of liver cells were observed; transmission electron microscopy showed varying degrees of mitochondria swelling up in liver cells in the other groups. At the same time, the expressions of AMPK, Beclin 1 and LC3 mRNA were increased, but the expressions of mTOR and p62 mRNA were decreased; the protein expressions of p-AMPK, Beclin 1, LC3-B were increased significantly, but those of p-mTOR and p62 were decreased (all P＜0.05). Compared with DMSO group, the injury of liver tissue in 3-MA group was alleviated, the damage degree of mitochondrial ultrastructure was lower, the levels of AST and ALT were decreased, the transcription and protein expression levels of autophagy related protein in liver tissue were decreased (P＜0.05). However, the injury degree of IR and DMSO groups were similar, and there was no significant differences in each index (P＞0.05). Conclusion: Lung ischemia/reperfusion can cause liver injury in rats. Autophagy can mediate liver injury induced by lung ischemia / reperfusion in rats and inhibiting autophagy can effectively reduce liver injury induced by LI/R in rats.

Clinical Features, Treatment, and Prognostic Factors in Neuronal Surface Antibody-Mediated Severe Autoimmune Encephalitis.

Objective: This study aimed to determine the clinical characteristics and evaluate the efficacy of immunotherapy and the long-term prognosis of severe autoimmune encephalitis (AE) in China. Methods: Clinical features, laboratory or radiological findings, and treatment outcomes of 60 severe patients with AE from January 1, 2014, to December 31, 2020, were collected. Continuous variables were compared using the t-test and the nonparametric Mann-Whitney U test, as appropriate. Univariate and multivariable logistic regression analyses were performed to assess the correlations between factors, treatment responses, and prognosis of severe AE. Results: The median age of symptom onset was 35 years. Tumors were identified in 23.3% of patients, and 36/60 (60%) patients responded to first-line immunotherapy. Second-line immunotherapy was implemented in 26/60 (43.3%) patients. A significant clinical benefit was observed in 19/26 (73.1%) patients treated with lower dosage rituximab; seven patients were still refractory and received bortezomib as an add-on therapy. During the last follow-up, 48/60 (80%) patients achieved good outcomes (mRS, 0-2), and 10 died. Seventeen patients experienced relapses. A high CD19+ B-cell count (OR, 1.197; 95% CI [1.043-1.496]; p = 0.041) and a lower neutrophil-to-lymphocyte ratio (NLR; OR, 0.686; 95% CI [0.472-0.884]; p = 0.015) predict the response to first-line treatment and good prognosis, respectively. Conclusions: Patients with severe AE were in critical condition at baseline but could be salvaged after effective rescue immunotherapy. A lower dosage of rituximab could be an optimal option for severe AE. CD19+ B-cell count and NLR may provide prognostic information for predicting treatment response and outcome of severe AE.

Influential Factors, Treatment and Prognosis of Autoimmune Encephalitis Patients With Poor Response to Short-Term First-Line Treatment.

Objective: This study was performed to assess the potential factors for poor short-term first-line treatment response, the appropriate further treatment options, and the prognosis in patients with autoimmune encephalitis (AE). Methods: This retrospective study consisted of 135 patients with AE. According to their short-term first-line treatment response, patients were divided into the response group and the non-response group. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and outcomes of patients were compared between the two groups. Univariate and multivariate logistic regression models were used to analyze whether non-responders have poor long-term outcomes. Further treatment and prognosis of non-responders were also analyzed. Results: Of the 128 patients who were treated with first-line immunotherapy, 59 (46.1%) were non-responders. Patients in the non-response group had more symptoms and exhibited a higher proportion of mental behavior disorder, central hypoventilation, and autonomic nervous dysfunction. The modified Rankin scale (mRS) scores and neutrophil-to-lymphocyte ratio (NLR) levels were significantly higher and albumin, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (apoA) levels were significantly lower in the non-response group (p < 0.05, all). Multivariate logistic regression analysis showed that the number of clinical symptoms, mental behavior disorder, central hypoventilation, maximum mRS score, and albumin level was independently associated with non-response to short-term first-line treatment. Non-responders had poor long-term outcomes compared with the responders at all times of followed-up (p < 0.05, all). In multivariable analysis, initial first-line treatment response was independently associated with the long-term prognosis, both at 12-month [odds ratio (OR), 4.74, 95% CI, 1.44-15.59, and p=0.010] and 24-month follow-ups (OR, 8.81, 95% CI, 1.65-47.16; and p = 0.011). Among the non-responders, a higher improvement of mRS scores was observed in those who received second-line treatment than those who had no further treatment or repetition of first-line immunotherapy in the follow-up. However, the rate of a good outcome and median mRS scores were not significantly different among the three groups. Conclusion: Disease severity, clinical features, anti-N-methyl-D-aspartate receptor subtypes, antibody titers, NLR, albumin, HDL-C, and apoA levels were all associated with non-response to short-term first-line treatment. The short-term first-line treatment response is a valuable predictor of long-term outcomes in patients with AE. Second-line immunotherapy may be a more aggressive treatment option for patients who failed short-term first-line immunotherapy.

LncRNA SNHG8 sponges miR-449c-5p and regulates the SIRT1/FoxO1 pathway to affect microglia activation and blood-brain barrier permeability in ischemic stroke.

Ischemic stroke (IS) can cause disability and death, and microglia as the immune component of the CNS can release inflammatory factors and participate in blood-brain barrier (BBB) dysfunction. This study aimed to investigate the effects of long noncoding RNA (lncRNA) SNHG8 on microglia activation and BBB permeability in IS. A rat model of permanent middle cerebral artery occlusion (p-MCAO) and a cell model of oxygen and glucose deprivation (OGD) in microglia were established, followed by evaluation of neurobehavioral function, BBB permeability, brain edema, and pathologic changes of microglia in brain tissue. The activation status of microglia and expressions of inflammatory factors were detected. Cell viability and integrity of microglia membrane were assessed. The downstream microRNA (miR), gene, and pathway of SNHG8 were analyzed. LncRNA SNHG8 was down-regulated in MCAO rats. Overexpression of SNHG8 improved the neural function defect, reduced brain water content, BBB permeability, brain tissue damage and inflammation, and inhibited microglia activation. In OGD-induced microglia, overexpression of SNHG8 or miR-449c-5p down-regulation increased cell viability and decreased lactate dehydrogenase activity. Moreover, SNHG8 sponged miR-449c-5p to regulate SIRT1. Overexpression of SNHG8 increased the expression of SIRT1 and FoxO1. MiR-449c-5p mimic could annul the effect of SNHG8 overexpression on ischemic microglia. Collectively, SNHG8 inhibits microglia activation and BBB permeability via the miR-449c-5p/SIRT1/FoxO1 pathway, thus eliciting protective effects on ischemic brain injury.

LINC00665 functions as a competitive endogenous RNA to regulate AGTR1 expression by sponging miR­34a­5p in glioma.

Glioma is the most aggressive tumor of the central nervous system. Long non­coding RNAs (lncRNAs) may be involved in modulating tumor generation. The present study analyzed an lncRNA microarray of glioma and selected long intergenic non­protein coding RNA 665 (LINC00665) as the research object. The mode of expression and biological function of LINC00665 in glioma were assessed using lncRNA microarray and RT­qPCR analyses. Gain­of­function assays and/or loss­of­function assays were implemented to explore the role of LINC00665 in the progression of glioma. Dual­luciferase reporter and RNA immunoprecipitation assays explored the downstream molecular mechanism of LINC00665. The function of the molecular pathway in progression of glioma was analyzed using rescue assays. High expression of LINC00665 was marked in glioma tissues and cells, which correlated with an unsatisfactory prognosis. Upregulation of LINC00665 significantly promoted the proliferation and invasion of glioma cells. LINC00665 acted as a competing endogenous RNA by sponging miR­34a­5p to upregulate angiotensin II receptor type 1 (AGTR1). LINC00665 promoted the progression of glioma by acting as a competitive endogenous RNA to competitively bind to miR­34a­5p and mediate AGTR1 expression.

MiRNA-190 exerts neuroprotective effects against ischemic stroke through Rho/Rho-kinase pathway.

Ischemic stroke is an urgent public health concern and one of the major causes of deaths and disabilities over the world. MicroRNA (miRNA) has become a key mediator of cerebral ischemia-reperfusion (I/R) injuries. However, whether miR-190 is involved in cerebral I/R-induced neuronal damage remains unknown. This study was to investigate the role of miR-190 in the brain I/R injury. We divided the rats into sham, I/R, control, and miR-190-mim (miR-190 mimics) groups. Quantitative real-time polymerase chain reaction (qRT-PCR), Nissl staining, flow cytometry, and western blot were conducted to examine the expression of miR-190 and cell apoptosis in different groups. The results showed that the expression of miR-190 was greatly decreased in rats suffering with I/R. Overexpression of miR-190 significantly reduced the increased neurological scores, brain water contents, infarct volumes, and neuronal apoptosis in rats suffering with I/R. In addition, we found that the expression of RhoA and Rho kinase was greatly elevated in rats suffering with I/R. Bioinformatics analysis indicated that Rho was a target of miR-190. Moreover, overexpression of miR-190 significantly downregulated the increased mRNA and protein expression of Rho/Rho kinase and cell apoptosis, while inhibition of miR-190 further upregulated the increased mRNA and protein expression of Rho/Rho kinase and cell apoptosis in rats suffering with I/R. Furthermore, knockdown of Rho significantly downregulated the increased mRNA and protein expression of Rho/Rho kinase and cell apoptosis, while these effects were inhibited by miR-190 inhibitors in rats suffering with I/R. These results indicate that miR-190 confers protection against brain I/R damage by modulating Rho/Rho-kinase signaling.

Association of KCNJ10 variants and the susceptibility to clinical epilepsy.

We first enrolled the available case-control studies to investigate the genetic association between three polymorphisms (rs1130183, rs1890532, and rs2486253) of KCNJ10 (the potassium voltage-gated channel subfamily J member 10) gene and the susceptibility towards clinical epilepsy. We utilized the meta-analysis, FPRP (false-positive report probability) test, and the TSA (trial sequential analysis) for the data pooling and the evaluation of statistical power. Totally, eight eligible articles were finally included. For KCNJ10 rs1130183, compared with population-based controls, a reduced epilepsy risk in cases was observed in models of allelic T vs. C, heterozygotic CT vs. CC, dominant CT + TT vs. CC, carrier T vs. C [all OR (odds ratio) <1, P < 0.05, Benjamini & Hochberg-adjusted P < 0.05, bonferroni-adjusted P < 0.05]. There were similar results in the subgroup analysis of "Caucasian". The positive conclusion was also statistically supported by the result of the FPRP test and TSA. Nevertheless, no statistically significant differences between epilepsy cases and negative controls were detected in any comparison of KCNJ101890532 and rs2486253. In summary, it is possible that the CT genotype of KCNJ10 rs1130183 is related to a reduced clinical epilepsy susceptibility, especially in Caucasians. However, more sample sizes are still required for a more robust conclusion in different populations, and more adjusted factors should be considered.

The genetic effect of the ICAM1 (intercellular adhesion molecule 1) rs5498 polymorphism on the susceptibility towards multiple sclerosis.

In the present study, we included currently published evidence to comprehensively evaluate the influence of the rs5498 polymorphism within the ICAM1 (intercellular adhesion molecule 1) gene on the genetic risk of multiple sclerosis. STATA 12.0 software was utilized to carry out the heterogeneity assessment, association test, and Begg's test as well as the Egger's tests and sensitivity analyses. A total of 11 high-quality case-control studies were selected from the initially retrieved 2209 articles. The lack of high heterogeneity led to the use of a fixed-effect model in all genetic models. The results of the association test showed a reduced risk of multiple sclerosis in the allelic G vs A (Passociation = 0.036, OR = 0.91) and dominant AG+GG vs AA (Passociation = 0.042, OR = 0.85) but not in other genetic models (all Passociation > 0.05). In addition, the negative results were observed in further subgroup analyses based on ethnicity or Hardy-Weinberg equilibrium in all genetic models. Data from Begg's and Egger's tests further excluded the presence of remarkable publication bias, while sensitivity analysis data supported stable outcomes. Thus, we conclude that ICAM1 rs5498 may not be related to the risk of multiple sclerosis in Caucasian or Asian populations, which still merits further research.

[Effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion induced myocardial injury in mice].

OBJECTIVE: To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice. METHODS: Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (n=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot. RESULTS: Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (P<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (P<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA. CONCLUSIONS: The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.

[Effects of dexmedetomidine on hypoxia/reoxygenation injury-induced cell apoptosis and caspase-12 expression in A549 cells].

To investigate the effects of dexmedetomidine (DEX) on hypoxia/reoxygenation (H/R) injury-induced cell apoptosis and caspase-12 expression, A549 cells were randomly divided into 4 groups: control group, DEX group, H/R group and DEX+H/R group. Cells of control and DEX groups were cultured in the normoxic incubator for 30 h. Cells of H/R and DEX+ H/R groups were incubated in the anoxic cultivation for 6 h, followed by normoxic culture for 24 h, and DEX (1 nmol/L) was added into the culture medium in DEX and DEX+H/R groups. Morphological changes were observed under the inverted microscope. Cell viability was detected by CCK-8. The apoptosis index (AI) of A549 cells was detected by TUNEL method. The activity of caspase-3 enzyme in cells was detected by using caspase-3 kit. The expressions of GRP78, caspase-12 protein and mRNA were determined by Western blot and RT-PCR respectively. Compared with control group, the morphological changes of the cultured cells were observed: some of the cell fusion occurred and the shape of the cells was multilateral; the cell viability was decreased significantly (P < 0.01), the number of apoptotic cells and the AI value, caspase-3 activity, and the expressions of GRP78, caspase-12 protein/mRNA were significantly increased (P < 0.01) in H/R group. While the administration of DEX alleviated the H/R injury-induced cell damage, obviously increased the cell viability (P < 0.01), significantly decreased the increment of apoptotic cells and the AI value induced by H/R injury (P < 0.01), and also dramatically decreased the H/R injury-induced high level of caspase-3 activity (P < 0.01) as well as high expression of caspase-12 protein and mRNA (P < 0.01). Taken together, the results suggest that DEX can effectively protect A549 cells from the H/R injury, which may be mediated by down-regulating the expression of caspase-12 and inhibiting cell apoptosis.

[The effects of YHTJF on lung ischemia/reperfusion injury in mice].

OBJECTIVE: To explore whether yiqi huoxue tongluo jiedu fang (YHTJF, Traditional Chinese Medicine) alleviates the injury during lung ischemia/reperfusion (I/R) in mice through inhibiting oxidative stress or not. METHODS: C57BL/6J male mice (n=70) were randomly divided into 7 groups:control (C), carboxyl methyl cellulose-Na(CMC·Na) + normal control (CC), carboxyl methyl cellulose-Na + sham (CS), carboxyl methyl cellulose-Na + I/R (CIR), carboxyl methyl cellulose-Na + YHTJF-Low, CMC-Na + YHTJF-Middle, CMC-Na + YHTJF-High (CYL, CYM, CYH). The mice in CYL, CYM and CYH group were treated with YHTJF by intraperitoneal injection every day, while the carboxyl methyl cellulose-Na was administered with the same volume of CYL in CC, CS and CIR group. After 3 h-reperfusion, the left lung tissues were harvested to determine the lung wet/dry weight (W/D), the total lung water content (TLW), and the index of quantita-tive evaluation for alveolar damage (IQA). Morphological observation and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) were applied to evaluate the structural changes and the apoptosis index (AI) of the lung tissues. The expressions superoxide of dis-mutase(SOD), malondialdehyde(MDA) and myeloperoxidase(MPO) in the lung tissues were detected by kits. RESULTS: Compared with group C, the W/D, TLW, IQA, AI, lung tissue structural changes, and the expressions of MDA and MPO in group I/R were increased obviously (P < 0.01), and the expression of SOD was decreased, while there was no significant difference between group CC and CS. Compared with group I/R, the parameters of these experiments in group CYL, CYM, CYH were all decreased, and the expression of SOD was increased, while the reduction in group CYM was the most remarkable among them (P < 0.01). CONCLUSIONS: YHTJF may attenuate the I/R injury of the lung by the inhibition of apoptosis via ROS pathway.

Therapeutic efficacy of chlorogenic acid on cadmium-induced oxidative neuropathy in a murine model.

The aim of the present study was to determine whether chlorogenic acid (CA) is able to modulate cadmium (Cd)-induced oxidative brain damage. Cd-treated rats displayed numerous pathological effects, including the inhibition of acetylcholinesterase, elevated lipid peroxidation, the depletion of enzymatic and non-enzymatic antioxidants, the reduction of membrane-bound ATPase activity, mitochondrial dysfunction and DNA fragmentation. Pretreatment of the rats with CA significantly attenuated these effects. These results lead to the hypothesis that the mechanisms by which CA attenuates the effects of Cd-induced oxidative brain damage include the maintenance of antioxidant homeostasis, inhibition of the membrane effects and the perpetuation of mitochondrial dysfunction. These data support the potential of CA as a beneficial intervention in the prevention of heavy metal poisoning due to Cd exposure.

Triptolide Protects Against Ischemic Stroke in Rats.

Inflammatory response plays an important role in the pathogenesis of ischemic stroke and anti-inflammatory agents may provide a choice of treatment. Triptolide is reported to be anti-inflammatory. In this study, we investigated the effects of triptolide on cultured neuronal cell line in vitro and experimental ischemic stroke in vivo. Oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cells were incubated with triptolide. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion for 23 h. Results of this study showed that triptolide treatment reduced the OGD-induced cytotoxicity and apoptosis and blocked TNF-α-induced activation of NF-κB and p38MAPK in SH-SY5Y cells. Intraperitoneal injection of triptolide showed significant neuroprotective actions in stroke rats. Triptolide attenuated neurological deficit, brain infarct volume, and brain water content, and inhibited activation of NF-κB and p38MAPK. These data show that triptolide protects rats against ischemic cerebral injury via inhibiting NF-κB and p38MAPK signaling pathways.

Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats.

This study is to investigate the effects of human umbilical cord-mesenchymal stem cells (HUC-MSCs) transplantation combined with minimally invasive hematoma aspiration on neural functional recovery and p53 gene expression in rats with intracerebral hemorrhage (ICH). Collagenase type-IV was injected to the caudate nucleus of the rats to make ICH models. One hundred and twenty Sprague-Dawley rats with successful modeling were randomly divided into 4 groups, including the ICH group, hematoma aspiration group, HUC-MSCs transplantation group and HUC-MSCs transplantation combined with hematoma aspiration group (combination group). Neural functional status of the rats was assessed by modified neurological severity score (mNSS). Expression of p53 in the cerebral tissues surrounding ICH was detected by immunohistochemical assays. The scores of mNSS and the expression of p53 gene in the hematoma aspiration group, the HUC-MSCs transplantation group and the combination group were significantly lower than those in the ICH group at each indicated time point (p < 0.05). Intriguingly, mNSS scores and p53 expression in the combination group were significantly lower than those in the hematoma aspiration group on day 7, 14 and 30 (p < 0.05), and significantly lower than those in the HUC-MSCs transplantation group on day 14 and 30 (p < 0.05). HUC-MSCs transplantation combined with minimally invasive hematoma aspiration is more effective than either therapy alone in rats with ICH and could distinctly reduce the damage of nerve cells.

[Effect of curcumin on caspase-12 and apoptosis in pulmonary ischemia/reperfusion injury mice].

OBJECTIVE: To explore the effect of curcumin (CUR) on cycteinyl aspirate specific protease-12 (Caspase-12) and pneumocyte apoptosis in pulmonary ischemia/reperfusion (I/R) injury mice. METHODS: The in vivo unilateral in situ pulmonary I/R injury mouse model was established in C57BL/6J mice. Sixty experimental mice were randomly divided into six groups by random digit table, i. e., the sham-operation group (Sham), the I/R group, the I/R + dimethyl sulfoxide group (I/R + DMSO), the I/R + low dose CUR pre-treated group (I/R + CUR-100), the I/R + middle dose CUR pre-treated group (I/R + CUR-150), the I/R + high dose CUR pre-treated group (I/R + CUR-200), 10 in each group. Mice were euthanized and their left lungs were excised. Wet lung weight to dry lung weight (W/D) and the total lung water content (TLW) were tested. The morphological changes of the lung tissue were observed and index of quantitative evaluation for alveolar damage (IQA) detected under light microscope. The ultra-microstructure of the lung tissue was observed under electron microscope. The mRNA and protein expression levels of Caspase-12 and glucose regulated protein (GRP78) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Apoptosis index (AI) of the lung tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. RESULTS: Compared with the Sham group, expression levels of Caspase-12, GRP78 mRNA and protein all significantly increased in the I/R group (P < 0.05); W/D, TLW, IQA, and AI were all notably higher (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were notably observed in I/R group. Compared with the I/R + DMSO group, expression levels of GRP78 mRNA and protein were increasingly higher in the I/R + CUR-100 group, the I/R + CUR-150 group, and the I/R +CUR-200 group (P < 0.05), expression levels of Caspase-12 mRNA and protein were lower (P < 0.05); W/D, TLW, IQA, and AI also decreased (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were gradually alleviated in the I/R + CUR groups. CONCLUSION: CUR had better effect on the lung protection against I/R injury, which might be related to inhibition for pneumocyte apoptosis associated with Caspase-12 in excessive unfolded protein response (UPR).

Mutant of leucine-rich repeat kinase 2 is not associated with non-motor symptoms in Chinese Parkinson's disease patients.

Non-motor symptoms (NMS) are common in patients with Parkinson's disease (PD). However, little is known about NMS in patients with mutant of leucine-rich repeat kinase 2 (LRRK2). This study aimed to elucidate the relationship between NMS in Chinese PD patients and to ascertain if there were differences in NMS between PD patients and mutant of LRRK2. 200 sporadic PD (sPD) patients were recruited from a Provincial Hospital Affiliated to Shandong University. The Non-motor Symptom Questionnaire (NMSQ) was used to screen for the presence of NMS. A mean of 9.73 NMS (SD=4.53) was reported per patient. Forgetfulness, constipation and daytime sleepiness were found to be the most frequent NMS. No differences were found in 9 domains analysis between PD with and without LRRK2 variants. Non-motor symptoms in PD are too important to remain undetected. There are no Clinical characteristics of NMS tend to be similar between LRRK2 variants carriers and non-carriers in Chinese sPD patients.