Advances in Engineered Nanoparticles for the Treatment of Ischemic Stroke by Enhancing Angiogenesis.

Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment.

Anti-TIM1 suppresses airway inflammation and hyperresponsiveness via the STAT6 /STAT1 pathways in mice with allergic asthma.

T cell immunoglobulin and mucin domain-1 (TIM-1) is a transmembrane glycoprotein and has been reported as an molecular mechanism of allergic diseases. This study aimed to explore the effects of anti-TIM-1 monoclonal antibodies (anti-TIM1) on the development of allergic asthma. Female C57BL/6 mice were induced and challenged with ovalbumin (OVA) and received subsequent intranasal administration of anti-TIM1. The airway resistance of all mice was evaluated using a Buxco PFT system. Flow cytometry was used to detect the expression of TIM-1 in peripheral blood mononuclear cells. The level of cytokine production in the bronchial alveolar lavage fluid and serum was determined using ELISA. Mucous cells were observed using Alcian blue and periodic acid-Schiff staining. In addition, B-cell lymphoma gene 2(BCL2), T-box transcription factor (T-bet), GATA binding protein-3(GATA3), signal transducer and activator of transcription (STAT) 1, STAT6 were analyzed by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. The mRNA expression level of Mucin 5AC in the lung tissues was also detected using quantitative RT-PCR. The results showed that the intranasal administration of anti-TIM1 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Following administration of anti-TIM1, both the mRNA and protein levels of T-bet were upregulated, while those of BCL2 and GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT6 were increased. Taken together, these findings demonstrated that intranasal administration of anti-TIM1 ameliorated allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT6 pathways.

Effects of Depression, Anxiety, Stigma, and Disclosure on Health-Related Quality of Life among Chronic Hepatitis B Patients in Dalian, China.

Chronic hepatitis B virus (HBV) infection is a major public health problem in China. We evaluated the impact of psychosocial factors (stigma, disclosure, depression, and anxiety) on health-related quality of life (HRQoL) among people living with chronic HBV infection (CHB) in the city of Dalian, Liaoning Province, China. In this hospital-based cross-sectional study, 401 patients living with chronic HBV infection were enrolled as study participants. Study measures included the Beck depression and anxiety inventory, the WHO Quality of Life (WHOQOL-BREF) assessment, the Toronto Chinese HBV Stigma Scale, and disclosure of HBV status to sexual partners. The primary outcome was HRQoL score as measured by the WHOQOL-BREF. A linear regression model was used to examine the association between HRQoL and the potential risk factors including stigma, disclosure, depression, anxiety, and sociodemographic variables. Stigma, disclosure, depression, and anxiety were the covariates of interest. A majority of the participants were females (n = 251, 65.6%), married (81.6%), and had a college or higher degree (32.4%). Depression, anxiety, stigma, and disclosure of HBV infection were associated with low HRQoL in all four domains of the WHOQOL-BREF (physical, psychological, social, and environmental domains) (P < 0.05), when all psychological factors were included in the model separately. Depression was found to be independently associated with low HRQoL in people living with HBV, when all psychological factors were included in the model simultaneously (P < 0.0001). Our data indicate the urgent need for healthcare providers (HCPs) and policy-makers to implement psychological interventions to improve HRQoL among people living with CHB.

A study on spleen transient elastography in predicting the degree of esophageal varices and bleeding.

This study aims to investigate the value and determine the accuracy of spleen stiffness in predicting the degree of esophageal varices and bleeding in patients with liver cirrhosis.The age, gender, liver stiffness, spleen stiffness, and gastroscopy results of 124 inpatients or outpatients with liver cirrhosis and healthy volunteers, who underwent both gastroscopy and FibroScan testing in the fasting state, were retrospectively analyzed. According to the gastroscopy results, the patients and healthy volunteers were divided into six groups: varicose bleeding, severe varices, moderate varices, mild varices, no varices, and healthy control group. Then, the receiver operating characteristic curves were drawn, and the corresponding area under each curve was calculated and evaluated to predict the severity of varices based on the relevance of the area and its parameters.The area under the receiver operating characteristic curve of liver stiffness and spleen stiffness for predicting severe and moderate varices in the bleeding group was 0.955 and 0.989, respectively. The cut-off values were 29.6 kPa and 45.5 kPa, respectively. The area under the receiver operating characteristic curve of liver stiffness for predicting varicose bleeding was 0.860 (95% CI: 0.789-0.931). The liver stiffness cut-off value for predicting varicose bleeding was 33.2 kPa, with a specificity and sensitivity of 66.02% and 95.24%, respectively. The area under the receiver operating characteristic curve of spleen stiffness for predicting varicose bleeding was 0.923 (95% CI: 0.875-0.971). A spleen stiffness cut-off value of 55.2 kPa had a sensitivity and specificity of 90.48% and 86.41%, respectively.Spleen stiffness can predict the degree of esophageal varices and bleeding in liver cirrhosis patients, and has good predictive accuracy.

Efficacy and safety of oxaliplatin-based regimen versus cisplatin-based regimen in the treatment of gastric cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Cisplatin played an important role in the treatment of gastric cancer (GC). Oxaliplatin has been shown to be at least as effective as cisplatin for GC, with less toxicity and a better tolerability profile. We performed a meta-analysis to compare the efficacy and safety of oxaliplatin-based regimen versus cisplatin-based regimen in the treatment of GC. METHODS: Databases of CNKI, CBM, VIP, Wanfang, PubMed, Embase, Cochrane Library were searched for eligible literatures from their establishments to November 2018. Randomized controlled trials that compared the efficacy and safety of oxaliplatin-based regimen with that of cisplatin-based regimen in the treatment of GC were included. Statistical analyses were calculated using RevMan 5.3 software. RESULTS: Seven randomized controlled trials including 2297 patients were included. Compared with cisplatin-based regimen intervention in GC, oxaliplatin-based regimen treatment was able to significantly improve the partial response rate (OR = 1.26, 95% CI 1.07-1.49; p = 0.007), disease progression rate (OR = 0.41, 95% CI 0.25-0.66; p = 0.0002) and 1-year survival (OR = 1.25, 95% CI 1.00-1.56; p = 0.05). The toxicities of hematopoietic system were significantly higher in cisplatin-based regimen group (OR = 0.6, 95% CI 0.46-0.79; p = 0.0002), while oxaliplatin-based regimen group had higher neurosensory toxicity (OR = 2.21, 95% CI 1.52-3.21; p < 0.0001), In addition, gastrointestinal toxicity was similar between the two groups (OR = 1.01, 95% CI 0.5-2.01; p = 0.27). CONCLUSIONS: Compared with cisplatin-based regimen, oxaliplatin-based regimen treatment has an obvious advantage in patients with GC with acceptable tolerance.

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.