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Schizophrenia is associated with an increased risk of metabolic syndrome (MetS), which is an important risk factor for developing cognitive impairment in the general population. A few case-control studies have explored the relationship between MetS and cognitive deficits in individuals with schizophrenia but with inconsistent findings. This meta-analysis of case-control studies was carried out to explore the association between MetS and cognitive performance in patients with schizophrenia. Only case-control studies assessing the association of cognitive function and MetS in patients with schizophrenia were identified. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale. Six case-control studies (n = 992) comparing cognition between patients with schizophrenia with MetS (n = 426) and those without MetS (n = 566) using the RBANS were identified. Compared to patients with schizophrenia without MetS, patients with schizophrenia and MetS had significantly more impairments in RBANS total scores [standardized mean difference (SMD) = −0.26, 95% confidence interval (CI): −0.51 to −0.02; I2 = 72%; p = 0.03], immediate memory (SMD = -0.32, 95% CI: −0.54 to −0.10; I2 = 66%; p = 0.005), attention (SMD = -0.29, 95% CI: −0.56 to −0.02; I2 = 77%; p = 0.03), and delayed memory (SMD = -0.24, 95% CI: −0.46 to −0.03; I2 = 64%; p = 0.03). No group difference was found regarding visuospatial skills and language (p > 0.05). This meta-analysis found that schizophrenia patients with MetS had worse performance on certain cognitive tasks than non-MetS patients.

This study investigates impacts of polices on dynamic linkages between the Chinese stock and real estate markets between June 2010 and November 2016. By using the Generalized Autoregressive Conditi...

The molecular basis for group I metabotropic glutamate receptors (mGluR1 and 5) coupling to membrane ion channels and intracellular calcium pools is not fully understood. Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. In the present study, we demonstrate that Homer1b/c is constitutively expressed in PC12 cells, whereas Homer1a, the immediate early gene product, can be up-regulated by brain derived neurotrophic factor (BDNF) and glutamate. Knockdown of Homer1b/c using specific target small interfering RNA (siRNA) did not interfere the expression of mGluR1, mGluR5 and their downstream effectors, including inositol-1,4,5-trisphosphate receptors (IP3R), phospholipase C (PLC) and Gq proteins. By analyzing Ca(2+) imaging in PC12 cells, we demonstrated that Homer1b/c is an essential regulator of the Ca(2+) release from the endoplasmic reticulum (ER) induced by the activation of group I mGluRs, IP3R and ryanodine receptors (RyR). Furthermore, the group I mGluRs activation-dependent refilling of the Ca(2+) stores in both resting and depolarizing conditions were strongly attenuated in the absence of Homer1b/c. Together, our results demonstrate that in PC12 cells Homer1b/c is a regulator of group I mGluRs related Ca(2+) homeostasis that is essential for the maintenance of normal Ca(2+) levels in the ER.

Inflammation and immunity are important in the pathogenesis of cerebral ischemia. Toll-like receptor 4 (TLR4) is involved in the inflammatory responses of injured brain tissues. Emerging studies have focused on the effect of isoflurane (ISO) pretreatment on cerebral ischemia, however, the association between ISO pretreatment and TLR4 during cerebral ischemia remains to be elucidated. In the present study, the protective role of ISO pretreatment in rats with focal cerebral ischemia reperfusion was investigated and the molecular mechanism was discussed. Using a middle cerebral artery occlusion (MCAO) model, triphenyltetrazolium chloride staining was utilized to measure the infarct volume and brain edema and immunofluorescence staining was used to detect the MCAO-induced TLR4 expression and localization. Western blot analyses were conducted to quantify the protein expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB in ischemic brain tissue at different time points. The results demonstrated that, following ISO pretreatment, the neurological deficits, brain edema and cerebral infarct size caused by ischemia/reperfusion were attenuated. The astrocyte and microglial activation in the brain tissue was decreased. In addition, the expression levels of TLR4, MyD88 and NF-κB were decreased. The present study indicated that ISO pretreatment may protect the brain from ischemic damage by downregulating the expression levels of TLR4, MyD88 and NF-κB.

The molecular basis for group I metabotropic glutamate receptors (mGluR1 and 5) coupling to membrane ion channels and intracellular calcium pools is not fully understood. Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. In the present study, we demonstrate that Homer1b/c is constitutively expressed in PC12 cells, whereas Homer1a, the immediate early gene product, can be up-regulated by brain derived neurotrophic factor (BDNF) and glutamate. Knockdown of Homer1b/c using specific target small interfering RNA (siRNA) did not interfere the expression of mGluR1, mGluR5 and their downstream effectors, including inositol-1,4,5-trisphosphate receptors (IP3R), phospholipase C (PLC) and Gq proteins. By analyzing Ca(2+) imaging in PC12 cells, we demonstrated that Homer1b/c is an essential regulator of the Ca(2+) release from the endoplasmic reticulum (ER) induced by the activation of group I mGluRs, IP3R and ryanodine receptors (RyR). Furthermore, the group I mGluRs activation-dependent refilling of the Ca(2+) stores in both resting and depolarizing conditions were strongly attenuated in the absence of Homer1b/c. Together, our results demonstrate that in PC12 cells Homer1b/c is a regulator of group I mGluRs related Ca(2+) homeostasis that is essential for the maintenance of normal Ca(2+) levels in the ER.

Osteosarcoma is the most common form of primary malignant bone tumor that mainly occurs in juvenile patients. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that p21 plays important roles in regulating tumor growth. To study the effects of p21 on the chemosensitivity of human osteosarcoma U2OS cells to cisplatin and its relevant mechanisms, we stably transfect the pC-21-SN3 vector containing P21 to U2O3 cells (U2O3-p21), which was identified by RT-PCR and Western blot. The results showed that no p21 was expressed in U2OS and U2OS-vec cells, but it was highly expressed in U2O3-p21 cells at mRNA and protein levels. The growth of U2OS cells was almost not influenced by p21 alone. However, U2O3-p21 cells underwent more obvious apoptotic morphological changes than U2OS and U2OS-vec cells after being treated with cisplatin (5 μg) for 72 h. Besides, increased expression of cleaved caspase-3 and Bax/Bcl-2 ratio was observed in cisplatin-treated U2O3-p21 cells. These data clearly indicated that exogenous p21 gene transfection could enhance the cisplatin-induced cytotoxicity against human osteosarcoma U2OS cells, at least in part, by activating caspase-3 cascade and increasing Bax/Bcl-2 ratio.

Chronic pain is one of the most common complications of diabetes. However, current treatments for diabetic pain are usually unrealistic because the underlying mechanisms are far from being clear. Immerging studies have implicated immune factors as key players in the diabetic pain. High-mobility group box 1 (HMGB1) is an important mediator of inflammatory response, but its role in diabetic pain is unclear. In the present study, we observed that db/db mice (a model of type 2 diabetes) developed persistent mechanical allodynia from postnatal 2 months. Western blot showed that in postnatal 2-5 months, HMGB1 was significantly higher than that of the heterozygous littermates (db/+) mice. Intrathecal injection of a HMGB1 neutralizing antibody (anti-HMGB1) inhibited mechanical allodynia. Immunostaining data showed that compared with db/+ and C57 mice (postnatal 4 months), glial fibrillary acidic protein (GFAP) staining was significantly increased in the spinal cord of db/db mice. Anti-HMGB1 could effectively decrease GFAP expression. Real-time PCR showed that in postnatal 4 months, db/db mice induced significant increases of TNF-alpha, IL-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in the spinal dorsal horn, while anti-HMGB1 (50 μg) effectively inhibited the up-regulation of these inflammatory mediators. Our results indicate that HMGB1 is significantly up-regulated in the spinal cord of type 2 diabetes, and inhibiting HMGB1 may provide a novel treatment for diabetic pain.

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and "NO-Astrocyte-Cytokine-NMDAR-Neuron" pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.