We profiled the immune status in glioma and established a local immune signature for GBM, which could independently identify patients with a high risk of reduced survival, indicating the relationship between prognosis and local immune response.
In a swine model, renal denervation via the Symplicity Catheter System resulted in no clinically significant adverse renal artery or renal findings 6 months after the procedure. This is corroborated by the vascular safety profile demonstrated in subsequent human clinical studies.
IntroductionSuicide is a major public health concern and a leading cause of death around the world. How religion influences the risk of completed suicide in different settings across the world requires clarification in order to best inform suicide prevention strategies.MethodsA meta-analysis using search results from Pubmed and Web of Science databases was conducted following PRISMA protocol and using the keywords “religion” or “religious” or “religiosity” or “spiritual” or “spirituality” plus “suicide” or “suicidality” or “suicide attempt”. Random and fixed effects models were used to generate pooled ORs and I2 values. Sub-analyses were conducted among the following categories: young age (<45yo), older age (≥45yo), western culture, eastern culture, and religious homogeneity.ResultsNine studies that altogether evaluated 2339 suicide cases and 5252 comparison participants met all selection criteria and were included in the meta-analysis. The meta-analysis suggested an overall protective effect of religiosity from completed suicide with a pooled OR of 0.38 (95% CI: 0.21–0.71) and I2 of 91%. Sub-analyses similarly revealed significant protective effects for studies performed in western cultures (OR = 0.29, 95% CI: 0.18–0.46), areas with religious homogeneity (OR = 0.18, 95% CI: 0.13–0.26), and among older populations (OR = 0.42, 95% CI: 0.21–0.84). High heterogeneity of our meta-analysis was attributed to three studies in which the methods varied from the other six.ConclusionReligion plays a protective role against suicide in a majority of settings where suicide research is conducted. However, this effect varies based on the cultural and religious context. Therefore, public health professionals need to strongly consider the current social and religious atmosphere of a given population when designing suicide prevention strategies.
Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models.
Experimentation in shaken microplate formats offers a potential platform technology for the rapid evaluation and optimization of cell culture conditions. Provided that cell growth and antibody production kinetics are comparable to those found in currently used shake flask systems then the microwell approach offers the possibility to obtain early process design data more cost effectively and with reduced material requirements. This work describes a detailed engineering characterization of liquid mixing and gas-liquid mass transfer in microwell systems and their impact on suspension cell cultures. For growth of murine hybridoma cells producing IgG1, 24-well plates have been characterized in terms of energy dissipation (P/V) (via Computational Fluid Dynamics, CFD), fluid flow, mixing and oxygen transfer rate as a function of shaking frequency and liquid fill volume. Predicted k(L)a values varied between 1.3 and 29 h(-1); liquid-phase mixing time, quantified using iodine decolorization experiments, varied from 1.7 s to 3.5 h; while the predicted P/V ranged from 5 to 35 W m(-3). CFD simulations of the shear rate predicted hydrodynamic forces will not be detrimental to cells. For hybridoma cultures however, high shaking speeds (>250 rpm) were shown to have a negative impact on cell growth, while a combination of low shaking speed and high well fill volume (120 rpm, 2,000 microL) resulted in oxygen limited conditions. Based on these findings a first engineering comparison of cell culture kinetics in microwell and shake flask formats was made at matched average energy dissipation rates. Cell growth kinetics and antibody titer were found to be similar in 24-well microtiter plates and 250 mL shake flasks. Overall this work has demonstrated that cell culture performed in shaken microwell plates can provide data that is both reproducible and comparable to currently used shake flask systems while offering at least a 30-fold decrease in scale of operation and material requirements. Linked with automation this provides a route towards the high throughput evaluation of robust cell lines under realistic suspension culture conditions.
We have investigated the possibility that photoexcited titanium dioxide (TiO2) could inhibit the growth of malignant cells. We studied the anti-glioma effects of nano-TiO2 excited with ultraviolet A (UVA) irradiation both in vitro and in vivo. Transmission electron microscopy demonstrated that glioma cells take up TiO2 by phagocytosis, and vital staining revealed that TiO2 alone has no effect on glioma cell proliferation. However, if TiO2 was combined with UVA irradiation the proliferation rate was decreased significantly compared to controls (P<0.05). RT-PCR suggested that TiO2 induction of glioma cell apoptosis is associated with changes in the expression of genes encoding Bcl-2 family members. We then investigated the in vivo antitumor effects of combined TiO2 plus UVA treatment of established glioma tumors. TiO2 plus UVA led to pronounced areas of necrosis, elevated indices of apoptosis, delayed tumor growth, and increased survival compared with the TiO2-alone control group (P<0.001). Log-rank survival analysis showed that median survival duration was prolonged (P<0.001). These findings suggest that nano-TiO2 based photodynamic therapy has potential in the treatment of glioma.
Familial idiopathic basal ganglia calcification (FIBGC) is a rare, autosomal dominant disorder involving bilateral calcification of the basal ganglia. To identify gene mutations related to a Chinese FIBGC lineage, we evaluated available individuals in the family using CT scans. DNA was extracted from the peripheral blood of available family members, and both exonic and flanking intronic sequences of the SLC20A2 gene were amplified by PCR and then sequenced. Non-denaturing polyacrylamide gel electrophoresis (PAGE) was used to confirm the presence of mutations. Allele imbalances of the SLC20A2 gene or relative quantity of SLC20A2 transcripts were evaluated using qRT-PCR. A novel heterozygous single base-pair deletion (c.510delA) within the SLC20A2 gene was identified. This deletion mutation was found to co-segregate with basal ganglia calcification in all of the affected family members but was not detected in unaffected individuals or in 167 unrelated Han Chinese controls. The mutation will cause a frameshift, producing a truncated SLC20A2 protein with a premature termination codon, most likely leading to the complete loss of function of the SLC20A2 protein. This mutation may also lead to a reduction in SLC20A2 mRNA expression by approximately 30% in cells from affected individuals. In conclusion, we identified a novel mutation in SLC20A2 that is linked to FIBGC. In addition to the loss of function at the protein level, decreasing the expression of SLC20A2 mRNA may be another mechanism that can regulate SLC20A2 function in IBGC individuals. We propose that the regional expression pattern of SLC20A1 and SLC20A2 might explain the unique calcification pattern observed in FIBGC patients.
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