Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

cbx2 is a functional target of the let-7 family in the gonad of Japanese flounder (Paralichthys olivaceus).

As a key member of the miRNA family, the role and target gene of the let-7 family in the gonad of Japanese flounder (Paralichthys olivaceus) is unclear. Chromobox homolog 2 (CBX2) is one of the core components of the polycomb group complex (PcG) and significantly influences gonadal development. The deletion of CBX2 can lead to sex reversal in mammals. Therefore, exploring the relationship between the let-7 family and cbx2 is crucial to clarify the role played by the let-7 family in the gonad of Japanese flounder. We predicted and verified the target interaction between the let-7 family and cbx2. The results showed that cbx2 was a direct target of let-7d, let-7e, let-7g, let-7j, and let-7b. Among them, let-7d, let-7e, let-7g, and let-7j exhibited an extremely significant targeting relationship with cbx2 (p < 0.001). Taking let-7g as an example, we further investigated the regulatory role between let-7g and cbx2 in the gonad by miRNA overexpression and inhibition experiments in primary testis cells. The results revealed that let-7g could negatively regulate cbx2 at the level of primary testis cells. And the expression of sf1 (steroidogenic factor 1) was also significantly decreased after the interference of cbx2 siRNA. This suggests that the let-7 family may be involved in the Japanese flounder gonadal development via targeting cbx2.

Cbx2, a PcG Family Gene, Plays a Regulatory Role in Medaka Gonadal Development.

Chromobox homolog 2 (CBX2), a key member of the polycomb group (PcG) family, is essential for gonadal development in mammals. A functional deficiency or genetic mutation in cbx2 can lead to sex reversal in mice and humans. However, little is known about the function of cbx2 in gonadal development in fish. In this study, the cbx2 gene was identified in medaka, which is a model species for the study of gonadal development in fish. Transcription of cbx2 was abundant in the gonads, with testicular levels relatively higher than ovarian levels. In situ hybridization (ISH) revealed that cbx2 mRNA was predominately localized in spermatogonia and spermatocytes, and was also observed in oocytes at stages I, II, and III. Furthermore, cbx2 and vasa (a marker gene) were co-localized in germ cells by fluorescent in situ hybridization (FISH). After cbx2 knockdown in the gonads by RNA interference (RNAi), the sex-related genes, including sox9 and foxl2, were influenced. These results suggest that cbx2 not only plays a positive role in spermatogenesis and oogenesis but is also involved in gonadal differentiation through regulating the expression levels of sex-related genes in fish.

Relationship between Erk1/2 signal pathway and nerve cell apoptosis rats with ischemic stroke.

To investigate the relationship between the Erk1/2 signal pathway and neuronal apoptosis in ischemic stroke rats. Male SD(Sprague Dawley)  rats (n = 24) were randomly divided into three groups, each containing 8 rats: sham-operated group, MCAO(Midle cerebral artery oclusion)  group, and MCAO + U0126 intervention group (U0126 group). In in vitro trial, primary cortical nerve cells were divided into three groups: control group, OGD(Oxygen and glucose deprivation)  group, and U0126 intervention group (U0126 group). In vivo protein expression levels of Erk1/2, p-Erk1/2 and Bcl-2 were determined using western blot. The expressions of Bcl-2, Bcl-xl and Bax were assayed using immunohistochemical staining. Nerve cell mortality in cerebral tissue was detected using TUNEL staining. In in vitro trials, cell apoptosis was assayed with flow cytometry and LDH release. The activity of caspase-3 was determined. Nerve cell apoptosis was determined using Hoechst33258 staining method. In in vivo trial, it was found that the protein expression level of p-ERK1/2 in cerebral tissue in the MCAO group was significantly increased, when compared with that of the sham-operated group, while the protein expression level of p-Erk1/2 in the U0126 group was significantly lower than that in the MCAO group. The expression levels of Bcl-2 and Bcl-xl in the MCAO group were significantly lower than the corresponding expression levels in the sham-operated group, while the expressions of Bcl-2 and Bcl-xl in the U0126 group were significantly lower than those in MCAO group. In MCAO group, the expression of Bax was significantly higher than that in the sham-operated group, while Bax expression was higher in U0126 than in MCAO group. There were significantly higher number of dead nerve cells in MCAO group than in the sham-operated group, while nerve cell mortality in U0126 group was significantly lower than in MCAO group. In in vitro trials, flow cytometry revealed significantly higher apoptosis of OGD-treated nerve cells, relative to the control group. Nerve cells exposed to U0126 and treated with ODR (Oxygen-dependent repressor)  were significantly decreased in population, when compared with single OGD treatment group. The LDH release level of nerve cells treated OGD was significantly increased, when compared with that of the control group. However, LDH release level of nerve cells treated with OGD after U0126 intervention was significantly decreased, relative to the single OGD treatment group. The dilution of nerve cell nucleus after OGD treatment was significantly increased, when compared with that of the control group. For nerve cells treated with ODR after U0126 intervention, the nuclear dilution was significantly decreased, relative to that of nerve cell nucleus in the single OGD treatment group. The OGD treatment led to significant increase in nerve cell caspase-3 activity, relative the control group. However, the caspase-3 activity of nerve cells treated with ODR after U0126 intervention was significantly decreased, when compared with single OGD treatment group. The activation of Erk1/2 signal pathway during ischemic stroke promotes apoptosis of nerve cells. Based on these findings, it can be reasonably inferred that the ERK1/2 signal pathway may be an important target for treating ischemic stroke.

IMPA2 polymorphisms and risk of ischemic stroke in a northwest Han Chinese population.

Genetic association analysis has suggested that IMPA2 is a susceptibility gene for ischemic stroke (IS). To explore the association between IMPA2 polymorphisms and the risk of IS in a Han Chinese population, candidate gene association was performed using data from a case-control study of 488 IS patients and 503 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association, and associations were evaluated under dominant, recessive, and additive genetic models using PLINK software. There was a statistically significant difference in the "TC" genotype frequency of the IMPA2 polymorphism rs589247, between cases and controls (50.0% vs. 45.3%). Under the dominant model, rs589247 was associated with an increased risk of IS (OR=1.32, 95%CI: 1.01-1.73; P=0.040). There were no other associations between any of the seven additional IMPA2 polymorphisms and IS risk. This study is the first to find a correlation between an IMPA2 polymorphism and IS risk in a northwest Han Chinese population. These results may help to elucidate the molecular pathogenesis of this disease, and could potentially be used to predict IS risk. However, further studies are still needed to validate this association in other populations and with larger sample sizes.