Glioblastoma: Changing concepts in the WHO CNS5 classification

Glioblastoma is the most common malignant central nervous system (CNS) tumor in adults. Acute common clinical symptoms include headache, seizure, behavior changes, focal neurological deficits, and signs of increased intracranial pressure. The classic MRI finding of glioblastoma is an irregularly shaped, rim-enhancing or ring-enhancing lesion with a central dark area of necrosis. This constellation of features correlates with microscopic findings of tumor necrosis and microvascular proliferation. Besides these common features, several well-recognized histological subtypes include giant cell glioblastoma, granular cell glioblastoma, gliosarcoma, glioblastoma with a primitive neuronal component, small cell glioblastoma, and epithelioid glioblastoma. While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the fifth edition of the WHO Classification of Tumors of the Central Nervous System clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as “a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, Telomerase reverse transcriptase promoter mutation, Epidermal growth factor receptor gene amplification, +7/?10 chromosome copy-number changes (CNS WHO grade 4).”

Advances in the study of molecular identification technology of Echinococcus species

@#The larvae of Echinococcus (hydatidcyst) can parasitize humans and animals, causing a serious zoonotic disease-echinococcosis. The life history of Echinococcus is complicated, and as the disease progresses slowly after infection, early diagnosis is difficult to establish. Due to the limitations of imaging and immunological diagnosis in this respect, domestic and foreign scholars have established a variety of molecular detection techniques for the pathogen Echinococcus over recent years, mainly including nested polymerase chain reaction (PCR), multiplex PCR, real-time quantitative PCR, and nucleic acid isothermal amplification technology. In this article, the research progress of molecular detection technology for Echinococcus infection currently was reviewed and the significance of these methods in the detection and diagnosis of hydatid and hydatid diseases was also discussed.

Effects of different combinations of N, P and K at different time interval on vegetative, reproductive, yield and quality traits of mango (Mangifera Indica. L) cv. Dusehri / Efeitos de diferentes combinações de N, P e K em diferentes intervalos nas características vegetativas, reprodutivas, produtivas e de qualidade da manga (Mangifera indica. L) cv. Dusehri

The experiment was carried out on mango cv. Dusehri to investigate the effect of N, P and K fertilizers on vegetative, reproductive growth, yield and fruit quality. Eight different fertilizer combinations such as T1 (control), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) and T8 (NPK) were used. Individual or combine fertilizer application of N (1000 g), P (750 g) and K (750 g) were applied during growing season in February and August. All the treatments significantly influenced on vegetative growth, flowering, fruiting, yield and other physiochemical attributes of mango as compared to control. Least effect was observed with individual fertilizer application while combine fertilizer treatments enhanced most of the investigated parameters. Especially, qualitative traits showed nonsignificant differences between treated and untreated mango trees. However, among the different treatments T8 (NPK) showed significance for fruiting aspects such as maximum size of growth flushes (177.51 mm), total number of panicles/tree (845), total number of flowers/panicle (974), sex ratio (69.18%), fruit retention (13.85%), total number of fruits/tree (379), yield (82 kg/tree), fruit weight (197.5 g), pulp weight (135.5 g) and physiochemical parameters namely TSS (24.53), Vit. C (57.63 mg/100 mL) and total sugar (20.84%). In general, combine application of NPK (T8) were the most effective in enhancing fruiting aspects, yield, physiochemical characteristics as well as improved fruit quality of mango trees.

O experimento foi realizado em manga cv. Dusehri para investigar o efeito dos fertilizantes N, P e K no crescimento vegetativo, reprodutivo, produtividade e de qualidade do fruto. Foram utilizadas oito combinações diferentes de fertilizantes: T1 (controle), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) e T8 (NPK). Cada tratamento de N (1.000 g), P (750 g) e K (750 g) foi aplicado duas vezes durante a estação de crescimento em fevereiro e agosto. Todos os tratamentos influenciaram significativamente o crescimento vegetativo, floração, frutificação, produtividade e outros atributos físico-químicos da manga em relação ao controle. Menos efeito foi observado com a aplicação individual de fertilizante, enquanto os tratamentos combinados aumentaram a maioria dos parâmetros investigados. Especialmente as características qualitativas mostraram diferenças não significativas entre mangueiras tratadas e não tratadas. No entanto, entre os diferentes tratamentos, T8 (NPK) apresentou significância para aspectos de frutificação, como tamanho máximo de folgas de crescimento (177,51 mm), número total de panículas/árvore (845), número total de flores/panícula (974), razão sexual (69,18%), retenção de frutos (13,85%), número total de frutos/árvore (379), produção (82 kg/árvore), peso do fruto (197,5 g) e peso da polpa (135,5 g), além de parâmetros físico-químicos, como TSS (24,53), vitamina C (57,63 mg/100 mL) e açúcar total (20,84%). Em geral, a aplicação combinada de NPK (T8) foi a mais eficaz no aprimoramento dos aspectos de frutificação, produtividade, características físico-químicas, além da melhoria da qualidade dos frutos das mangueiras.

Effects of different combinations of N, P and K at different time interval on vegetative, reproductive, yield and quality traits of mango (Mangifera Indica. L) cv. Dusehri / Efeitos de diferentes combinações de N, P e K em diferentes intervalos nas características vegetativas, reprodutivas, produtivas e de qualidade da manga (Mangifera indica. L) cv. Dusehri

The experiment was carried out on mango cv. Dusehri to investigate the effect of N, P and K fertilizers on vegetative, reproductive growth, yield and fruit quality. Eight different fertilizer combinations such as T1 (control), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) and T8 (NPK) were used. Individual or combine fertilizer application of N (1000 g), P (750 g) and K (750 g) were applied during growing season in February and August. All the treatments significantly influenced on vegetative growth, flowering, fruiting, yield and other physiochemical attributes of mango as compared to control. Least effect was observed with individual fertilizer application while combine fertilizer treatments enhanced most of the investigated parameters. Especially, qualitative traits showed non significant differences between treated and untreated mango trees. However, among the different treatments T8 (NPK) showed significance for fruiting aspects such as maximum size of growth flushes (177.51 mm), total number of panicles/tree (845), total number of flowers/panicle (974), sex ratio (69.18%), fruit retention (13.85%), total number of fruits/tree (379), yield (82 kg/tree), fruit weight (197.5 g), pulp weight (135.5 g) and physiochemical parameters namely TSS (24.53), Vit. C (57.63 mg/100 mL) and total sugar (20.84%). In general, combine application of NPK (T8) were the most effective in enhancing fruiting aspects, yield, physiochemical characteristics as well as improved fruit quality of mango trees.

O experimento foi realizado em manga cv. Dusehri para investigar o efeito dos fertilizantes N, P e K no crescimento vegetativo, reprodutivo, produtividade e de qualidade do fruto. Foram utilizadas oito combinações diferentes de fertilizantes: T1 (controle), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) e T8 (NPK). Cada tratamento de N(1.000 g), P (750 g) e K (750 g) foi aplicado duas vezes durante a estação de crescimento em fevereiro e agosto. Todos os tratamentos influenciaram significativamente o crescimento vegetativo, floração, frutificação, produtividade e outros atributos físico-químicos da manga em relação ao controle. Menos efeito foi observado com a aplicação individual de fertilizante, enquanto os tratamentos combinados aumentaram a maioria dos parâmetros investigados. Especialmente as características qualitativas mostraram diferenças não significativas entre mangueiras tratadas e não tratadas. No entanto, entre os diferentes tratamentos, T8 (NPK) apresentou significância para aspectos de frutificação, como tamanho máximo de folgas de crescimento (177,51 mm), número total de panículas/árvore (845), número total de flores/panícula (974), razão sexual (69,18%), retenção de frutos (13,85%), número total de frutos/árvore (379), produção (82 kg/árvore), peso do fruto (197,5 g) e peso da polpa (135,5 g), além de parâmetros físico-químicos, como TSS (24,53), vitamina C (57,63 mg/100 mL) e açúcar total (20,84%). Em geral, a aplicação combinada de NPK (T8) foi a mais eficaz no aprimoramento dos aspectos de frutificação, produtividade, características físico-químicas, além da melhoria da qualidade dos frutos das mangueiras.

Effects of different combinations of N, P and K at different time interval on vegetative, reproductive, yield and quality traits of mango (Mangifera Indica. L) cv. Dusehri

Abstract The experiment was carried out on mango cv. Dusehri to investigate the effect of N, P and K fertilizers on vegetative, reproductive growth, yield and fruit quality. Eight different fertilizer combinations such as T1 (control), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) and T8 (NPK) were used. Individual or combine fertilizer application of N (1000 g), P (750 g) and K (750 g) were applied during growing season in February and August. All the treatments significantly influenced on vegetative growth, flowering, fruiting, yield and other physiochemical attributes of mango as compared to control. Least effect was observed with individual fertilizer application while combine fertilizer treatments enhanced most of the investigated parameters. Especially, qualitative traits showed non-significant differences between treated and untreated mango trees. However, among the different treatments T8 (NPK) showed significance for fruiting aspects such as maximum size of growth flushes (177.51 mm), total number of panicles/tree (845), total number of flowers/panicle (974), sex ratio (69.18%), fruit retention (13.85%), total number of fruits/tree (379), yield (82 kg/tree), fruit weight (197.5 g), pulp weight (135.5 g) and physiochemical parameters namely TSS (24.53), Vit. C (57.63 mg/100 mL) and total sugar (20.84%). In general, combine application of NPK (T8) were the most effective in enhancing fruiting aspects, yield, physiochemical characteristics as well as improved fruit quality of mango trees.

Resumo O experimento foi realizado em manga cv. Dusehri para investigar o efeito dos fertilizantes N, P e K no crescimento vegetativo, reprodutivo, produtividade e de qualidade do fruto. Foram utilizadas oito combinações diferentes de fertilizantes: T1 (controle), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) e T8 (NPK). Cada tratamento de N (1.000 g), P (750 g) e K (750 g) foi aplicado duas vezes durante a estação de crescimento em fevereiro e agosto. Todos os tratamentos influenciaram significativamente o crescimento vegetativo, floração, frutificação, produtividade e outros atributos físico-químicos da manga em relação ao controle. Menos efeito foi observado com a aplicação individual de fertilizante, enquanto os tratamentos combinados aumentaram a maioria dos parâmetros investigados. Especialmente as características qualitativas mostraram diferenças não significativas entre mangueiras tratadas e não tratadas. No entanto, entre os diferentes tratamentos, T8 (NPK) apresentou significância para aspectos de frutificação, como tamanho máximo de folgas de crescimento (177,51 mm), número total de panículas/árvore (845), número total de flores/panícula (974), razão sexual (69,18%), retenção de frutos (13,85%), número total de frutos/árvore (379), produção (82 kg/árvore), peso do fruto (197,5 g) e peso da polpa (135,5 g), além de parâmetros físico-químicos, como TSS (24,53), vitamina C (57,63 mg/100 mL) e açúcar total (20,84%). Em geral, a aplicação combinada de NPK (T8) foi a mais eficaz no aprimoramento dos aspectos de frutificação, produtividade, características físico-químicas, além da melhoria da qualidade dos frutos das mangueiras.

Dendritic cell TLR4 induces Th1-type immune response against Cryptosporidium parvum infection

@#The objective of this study was to investigate the mechanism of Toll-like receptor (TLR4)- mediated dendritic cell (DC) immune against Cryptosporidium parvum infection. C. parvum sporozoites were labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester. Murine bone marrow-derived DCs were isolated, and divided into TLR4 antibody blocking (TAB; infected with 2 × 105 labeled sporozoites and 0.5 μg TLR4 blocking antibody), TLR4 antibody unblocking (TAU; infected with 2 × 105 labeled sporozoites), and blank control (BC; with 1.5 mL Roswell Park Memorial Institute 1640 medium) groups. The adhesion of Cryptosporidium sporozoites to DCs and CD11c+ levels were examined by fluorescence microscopy and flow cytometry. Male KM mice were orally injected with C. parvum. The proliferation of T lymphocytes in spleen, expression of cytokines in peripheral blood, and TLR4 distribution features in different organs were further determined by immunohistochemistry. A significantly higher expression of CD11c+ and higher C. parvum sporozoite adhesion were found in the TAU group compared with other groups. The expression of CD4+CD8- /CD8+CD4- in the spleen were obviously differences between the TAB and TAU groups. The expression of TLR4, interleukin IL-4, IL-12, IL-18 and IFN-γ improved in the TAU group compared with TAB group. Higher expression of TLR4 was detected in the lymph nodes of mice in the TAU group, with pathological changes in the small intestine. Hence, TLR4 could mediate DCs to recognize C. parvum, inducing Th1 immune reaction to control C. parvum infection.

microRNAs expression profiles in Schistosoma japonicum of different sex 14 and 28 days post-infection

@#Different miRNAs are involved in the life cycles of Schistosoma japonicum. The aim of this study was to examine the expression profile of miRNAs in individual S. japonicum of different sex before and after pairing (18 and 24 dpi). The majority of differential expressed miRNAs were highly abundant at 14 dpi, except for sja-miR-125b and sja-miR-3505, in both male and female. Moreover, it was estimated that sja-miR-125b and sja-miR-3505 might be related to laying eggs. sja-miR-2a-5p and sja-miR-3484-5p were expressed at 14 dpi in males and were significantly clustered in DNA topoisomerase III, Rap guanine nucleotide exchange factor 1 and L-serine/L-threonine ammonia-lyase. Target genes of sja-miR-2d-5p, sja-miR-31- 5p and sja-miR-125a, which were expressed at 14 dpi in males but particularly females, were clustered in kelch-like protein 12, fructose-bisphosphate aldolase, class I, and heat shock protein 90 kDa beta. Predicted target genes of sja-miR-3483-3p (expressed at 28 dpi in females but not in males) were clustered in 26S proteasome regulatory subunit N1, ATPdependent RNA helicase DDX17. Predicted target genes of sja-miR-219-5p, which were differentially expressed at 28 dpi in females but particularly males, were clustered in DNA excision repair protein ERCC-6, protein phosphatase 1D, and ATPase family AAA domaincontaining protein 3A/B. Moreover, at 28 dpi, eight miRNAs were significantly up-regulated in females compared to males. The predicted target genes of these miRNAs were significantly clustered in heat shock protein 90 kDa beta, 26S proteasome regulatory subunit N1, and protein arginine N-methyltransferase 1. To sum up, differentially expressed miRNAs may have an essential role and provide necessary information on clarifying this trematode’s growth, development, maturation, and infection ability to mammalian hosts in its complex life cycle, and may be helpful for developing new drug targets and vaccine candidates for schistosomiasis.

Relationship between PI3K/mTOR/RhoA pathway-regulated cytoskeletal rearrangements and phagocytic capacity of macrophages

The objective of this study was to investigate the relationship between PI3K/mTOR/RhoA signaling regulated cytoskeletal rearrangements and phagocytic capacity of macrophages. RAW264.7 macrophages were divided into four groups; blank control, negative control, PI3K-RNAi, and mTOR-RNAi. The cytoskeletal changes in the macrophages were observed. Furthermore, the phagocytic capacity of macrophages against Escherichia coli is reported as mean fluorescence intensity (MFI) and percent phagocytosis. Transfection yielded 82.1 and 81.5% gene-silencing efficiencies against PI3K and mTOR, respectively. The PI3K-RNAi group had lower mRNA and protein expression levels of PI3K, mTOR, and RhoA than the blank and negative control groups (Р<0.01). The mTOR-RNAi group had lower mRNA and protein levels of mTOR and RhoA than the blank and the negative control groups (Р<0.01). Macrophages in the PI3K-RNAi group exhibited stiff and inflexible morphology with short, disorganized filopodia and reduced number of stress fibers. Macrophages in the mTOR-RNAi group displayed pronounced cellular deformations with long, dense filopodia and an increased number of stress fibers. The PI3K-RNAi group exhibited lower MFI and percent phagocytosis than blank and negative control groups, whereas the mTOR-RNAi group displayed higher MFI and percent phagocytosis than the blank and negative controls (Р<0.01). Before and after transfection, the mRNA and protein levels of PI3K were both positively correlated with mTOR and RhoA (Р<0.05), but the mRNA and protein levels of mTOR were negatively correlated with those of RhoA (Р<0.05). Changes in the phagocytic capacity of macrophages were associated with cytoskeletal rearrangements and were regulated by the PI3K/mTOR/RhoA signaling pathway.

Knocking down LSD1 inhibits the stemness features of colorectal cancer stem cells

As a top leading cause of cancer death in many countries, colorectal cancer (CRC) has drawn increasing attention to the study of the pathological mechanism. According to the "cancer stem cell hypothesis", malignancies originate from a small fraction of cancer cells that show self-renewal properties to initiate and sustain tumor growth and tumor metastasis. Therefore, these cancer stem cells (CSC) probably play important roles in tumor recurrence, metastasis, and drug resistance. Previous research reported that lysine-specific histone demethylase 1 (LSD1) maintains cancer stemness through up-regulating stemness markers SOX2 and OCT4. CD133 is believed to be the most robust surface marker for CRC stem cells, however the regulatory effect of LSD1 on stemness of CD133+ CRC has never been reported. In this study, our objectives included: 1) to isolate pure CD133+ and CD133− cells from SW620 cell line; 2) to investigate the effect of LSD1 on the characteristics of CD133+ stem cancer cells by knocking down the target gene. Results suggested that the SW620 cell line had both CD133+ and CD133− subsets. The CD133+ subset exhibited more CSC-like characteristics compared with the CD133− subset with higher viability, colony formation rate, migration and invasion rate, resistance to anti-cancer drugs, and apoptosis in vitro. The CD133+ also induced faster tumor formation and larger tumors in vivo. In the LSD1-knockdown CD133+ cells, the CSC-like characteristics had been all weakened. We conclude that LSD1 was important for CSCs to maintain their "stemness" features, which could be a potential therapeutic target of CRC.

Parasitological and molecular detection of human fascioliasis in a young man from Guizhou, China

@#A 24-year-old man born in Guizhou province was diagnosed with obstructive jaundice and bile duct stones in 2013. Four living trematodes were found during laparotomy and cholecystectomy. Based on the morphology and molecular genetics analysis of internal transcribed spacer and pcox1 genes of the flatworm specimens, the trematodes from the patient were confirmed to be Fasciola hepatica. This report provided the clinical and molecular diagnosis information on human fascioliasis, which is an emerging sanitary problem still ignored in China. Human fascioliasis constantly occurs due to climatic changes and frequency of human travel. Therefore, it deserves more attention from physicians working in both developing and developed countries.

Dual therapy with lopinavir/ritonavir plus lamivudine could be a viable alternative for antiretroviral-therapy-naive adults with HIV-1 infection regardless of HIV viral load or subgenotype in resource-limited settings: A randomised, open-label and non-inferiority study from China

Backgrounds: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-na飗e HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). Methods: 198 were randomised to DT (n = 100) or TT (n = 98). Results: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. Conclusion: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.

Comparison of outcomes between off-pump versus on-pump coronary artery bypass surgery in elderly patients: a meta-analysis

The aim of this study was to analyze if off-pump coronary artery bypass surgery (CABG) is associated with better treatment outcomes in elderly patients (>70 years of age) than on-pump CABG, using meta-analysis. Medline, PubMed, Cochrane and Google Scholar databases were searched until September 13, 2016. Sensitivity and quality assessment were performed. Twenty-two studies, three randomized control trials (RCTs) and 20 non-RCTs were included with 24,127 patients. The risk of death associated with on-pump or off-pump CABG in the RCTs were similar (pooled OR=0.945, 95%CI=0.652 to 1.371, P=0.766). However, in the non-RCTs, mortality risk was lower in patients treated with off-pump CABG than on-pump CABG (pooled OR=0.631, 95%CI=0.587 to 0.944, P=0.003). No differences were observed between the two treatment groups in terms of the occurrence of 30-day post-operative stroke or myocardial infarction (P≥0.147). In the non-RCTs, off-pump CABG treatment was associated with a shorter length of hospital stay (pooled standardized difference in means=-0.401, 95%CI=-0.621 to -0.181, P≤0.001). The meta-analysis with pooled data from non-RCTs, but not RCTs, found that mortality was lower with off-pump compared with on-pump CABG, and suggested that there may be some benefit of off-pump CABG compared with on-pump CABG in the risk of mortality and length of hospital stay.

Investigation on the nasal airflow characteristics of anterior nasal cavity stenosis

We used a computational fluid dynamics (CFD) model to study the inspiratory airflow profiles of patients with anterior nasal cavity stenosis who underwent curative surgery, by comparing pre- and postoperative airflow characteristics. Twenty patients with severe anterior nasal cavity stenosis, including one case of bilateral stenosis, underwent computed tomography (CT) scans for CFD modelling. The pre- and postoperative airflow characteristics of the nasal cavity were simulated and analyzed. The narrowest area of the nasal cavity in all 20 patients was located within the nasal valve area, and the mean cross-sectional area increased from 0.39 cm2 preoperative to 0.78 cm2 postoperative (P<0.01). Meanwhile, the mean airflow velocity in the nasal valve area decreased from 6.19 m/s to 2.88 m/s (P<0.01). Surgical restoration of the nasal symmetry in the bilateral nasal cavity reduced nasal resistance in the narrow sides from 0.24 Pa.s/mL to 0.11 Pa.s/mL (P<0.01). Numerical simulation of the nasal cavity in patients with anterior nasal cavity stenosis revealed structural changes and the resultant patterns of nasal airflow. Surgery achieved balanced bilateral nasal ventilation and decreased nasal resistance in the narrow region of the nasal cavity. The correction of nasal valve stenosis is not only indispensable for reducing nasal resistance, but also the key to obtain satisfactory curative effect.

MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Sequence variation and bioinformatics analysis of Toxoplasma gondii GRA16 Gene

Toxoplasmosis is caused by the intracellular protozoan Toxoplasma gondii. It is anopportunistic zoonosis in warm-blooded animals and humans, with a worldwide distribution. Toxoplasma gondii dense granule protein 16 (TgGRA16) can modulate some functions in host cells and is considered a significant virulent factor of the parasite. The present study reports sequence variation in TgGRA16 gene among T. gondii strains from different hosts and geographical locations, and the construction of phylogenetic relationships of these T. gondii strains based on sequences of TgGRA16, and analysis of B cell epitopes in TgGRA16. Our results showed that all TgGRA16 gene sequences were 1518 bp and the C+G contents ranged from 52.17% to 52.59%. Sequence variation in the TgGRA16 gene was 0-1.51%. Phylogenetic analysis revealed that TgGRA16 gene sequence could not be used to differentiate the different T. gondii genotypes. Six B cell epitopes were predicted in TgGRA16. These results indicated that TgGRA16 gene is not an ideal marker for studying genetic relationships of T. gondii isolates, but may represent a good vaccine candidate against toxoplasmosis.

Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer: A meta-analysis based on Chinese patients.

BACKGROUND: Colorectal carcinoma is one of most diagnosed solid malignant carcinoma. The chemotherapy combined with target drugs in the treatment of advanced colorectal cancer in not conclusive. METHODS: The clinical studies reporting the activity and adverse events between chemotherapy alone versus chemotherapy combined with anti‑epidermal growth factor receptor drugs were screened in the databases of Medline, the Cochrane Library, Wanfang and CNKI and included in this meta‑analysis. The risk ratio (RR) and its 95% confidence interval (CI) for treatment response and adverse events were pooled by random or fixed effect model. RESULTS: A total of 10 clinical studies reporting chemotherapy combined with the target in the treatment of advanced colorectal cancer were included in this study. The pooled RR was 3.26 (95% CI: 1.74–6.11, P < 0.05), 1.49 (95% CI: 1.23–1.80) and 1.65 (95% CI: 1.37–1.98) for complete response (CR), partial response and objective response rate, respectively. For nausea and vomiting events, the RR was 1.62 (95% CI: 1.33–1.97, P < 0.05) indicating higher incidence of nausea and vomiting was observed in the combined group compared with chemotherapy alone. However, the diarrhea (RR = 1.10, 95% CI: 0.86–1.42, P > 0.05), liver function damage (RR = 1.03, 95% CI: 0.74–1.42), myelosuppression (RR = 1.04, 95% CI: 0.83–1.31) and neurotoxicity (RR = 1.12, 95% CI: 0.93–1.35) were not different between the two groups. CONCLUSION: For Chinese patients with advanced colorectal cancer, chemotherapy combined with target drug can improve the response rate, but also increase the risk of nausea and vomiting.

ChIP-seq analysis of histone H3K9 trimethylation in peripheral blood mononuclear cells of membranous nephropathy patients

Membranous nephropathy (MN), characterized by the presence of diffuse thickening of the glomerular basement membrane and subepithelial in situ immune complex disposition, is the most common cause of idiopathic nephrotic syndrome in adults, with an incidence of 5-10 per million per year. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of human MN, but the specific biomarkers of MN have not been fully elucidated. As a result, our knowledge of the alterations in histone methylation in MN is unclear. We used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to analyze the variations in a methylated histone (H3K9me3) in peripheral blood mononuclear cells from 10 MN patients and 10 healthy subjects. There were 108 genes with significantly different expression in the MN patients compared with the normal controls. In MN patients, significantly increased activity was seen in 75 H3K9me3 genes, and decreased activity was seen in 33, compared with healthy subjects. Five positive genes, DiGeorge syndrome critical region gene 6 (DGCR6), sorting nexin 16 (SNX16), contactin 4 (CNTN4), baculoviral IAP repeat containing 3 (BIRC3), and baculoviral IAP repeat containing 2 (BIRC2), were selected and quantified. There were alterations of H3K9me3 in MN patients. These may be candidates to help explain pathogenesis in MN patients. Such novel findings show that H3K9me3 may be a potential biomarker or promising target for epigenetic-based MN therapies.