Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.
Heat tolerance can be improved by feed restriction in broiler chickens. It is unknown whether the same is true for broiler breeders, which are restrictedly fed. Therefore, the current study was conducted to study the effects of heat stress on plasma metabolites, hormones, and oxidative status of restricted fed broiler breeders with special emphases on the temperature and latency of heat exposure. In trial 1, 12 broiler breeders were kept either in a thermoneutral chamber (21°C, control, n = 6) or in a chamber with a step-wise increased environmental temperature from 21 to 33°C (21, 25, 29, 33°C, heat-stressed, n = 6). Changes in plasma total cholesterol, glucose, and triiodothyronine (T3) were closely related to the environmental temperature. When the temperature reached 29°C, plasma T3 (P < 0.05) was significantly decreased in acute heat-stressed birds, whereas plasma glucose (P < 0.001) and cholesterol (P = 0.002) increased only when the temperature reached 33°C. Plasma triglyceride (P = 0.026) and creatine kinase (CK, P = 0.018) were lower in heat-stressed birds than controls regardless of the temperatures applied. In Trial 2, 24 broiler breeders were divided into 2 groups and raised under 21°C and 32°C for 8 weeks, respectively. Total cholesterol was increased in chronic heat-stressed broiler breeders after 4 weeks. Plasma lactate dehydrogenase (LDH, P = 0.047) and glutamic-oxaloacetic transaminase (GOT, P = 0.036) was up-regulated after 6 weeks of thermal treatment, whereas plasma CK (P = 0.009) was increased at the end of thermal treatment. Plasma malonaldehyde, protein carbonyl content, activity of total superoxide dismutase (SOD), and corticosterone content were not altered after acute and prolonged heat challenges. Taken together, acute heat stress primarily resulted in disturbance of plasma metabolites, whereas chronic heat stress caused tissue damage reflected by increased plasma LDA, GOT, and CK. During acute heat stress, plasma metabolites were minimally disturbed in broiler breeders until the environmental temperature reached 33°C.
Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.
An experiment is conducted to investigate the effects of selenium (Se) source and level on growth performance, tissue Se concentrations, antioxidation, and immune functions of heat-stressed broilers from 22 to 42 days of age. A total of 210 22-day-old Arbor Acres commercial male chicks were assigned by body weight to one of seven treatments with six replicates of five birds each in a completely randomized design involving a 3 × 2 factorial arrangement plus one Se-unsupplemented basal diet control (containing 0.027 mg of Se/kg). The three Se sources were sodium selenite (Na₂SeO₃), Se yeast, and AMMS Se (Se protein), and the two supplemental Se levels were 0.15 or 0.30 mg Se/kg. All birds were reared under heat-stressed condition (33 ± 1 °C during 0900-1700 hours and 27 ± 1 °C during 1900-0700 hours with a relative humidity of 60-80 %). The results showed that heat-stressed chicks fed Se-supplemented diets had higher (P < 0.10) average daily feed intake, Se concentrations in liver and breast muscle, liver glutathione peroxidase (GSH-Px) activity, serum antibody titers against H5N1(Re-4 strain), H5N1(Re-5 strain) and lower (P < 0.01) mortality compared with the control. Chicks fed the diets supplemented with 0.30 mg/kg of Se had higher (P < 0.05) Se concentrations in liver and breast muscle, liver GSH-Px activity, and serum antibody titer against H5N1 (Re-4 strain) than those fed the diets supplemented with 0.15 mg/kg of Se. Broilers fed the diets supplemented with Se yeast had higher (P < 0.001) Se concentrations in liver and breast muscle than those fed the diets supplemented with Na₂SeO₃ or AMMS Se. However, broilers fed the diets supplemented with AMMS Se had higher (P < 0.05) serum antibody titers against H5N1 (Re-4 strain) and H5N1 (Re-5 strain) than those fed the diets supplemented with Na₂SeO₃. These results indicated that Se yeast was more effective than Na₂SeO₃ or AMMS Se in increasing tissue Se retention; however, AMMS Se was more effective than Na₂SeO₃ or Se yeast in improving immune functions of heat-stressed broilers.
Solar-driven interfacial evaporation system is attracting intensive attention for harvesting clean water in the utilization of solar energy. To improve solar-driven interfacial evaporation performance for better application, structuring a solar absorber with high solar–thermal conversion efficiency is critical. Semiconductor materials with stable and economic properties are good candidates as solar absorbers. Semiconductors with a narrow band gap have been proved to offer a broad solar absorption spectrum in the applications of photoelectricity and photocatalysis. However, the correlation between band gap and solar-driven interfacial evaporation performance has not been systematically studied. Herein, TiO2 is selected as a semiconductive absorber and a reproducible process is developed to fabricate band gap engineered TiO2 to understand the relationship between the “electronic structure” and the “performance” in the field of solar-driven interfacial evaporation. After the band gap engineering from 3.2 to 2.23 eV, correlative tests of solar-driven interfacial evaporation performance as well as first-principles calculations are employed to study the correlation mentioned above. As a result, we find that a narrower band gap contributes to improved solar–thermal conversion efficiency and the Ti3+-doped TiO2 (Ti3+-TiO2) with the narrowest band gap of 2.23 eV outperforms other samples, achieving the highest evaporation rate of 1.20 kg m–2 h–1 (solar–thermal conversion efficiency of 77.1%). Besides, the Ti3+-TiO2 also shows the good ability of photocatalytic degradation. This work may provide a way for semiconductor materials to be designed as solar absorbers with higher solar–thermal conversion efficiency and better solar-driven interfacial evaporation performance for applications in clean water harvesting.
In the present study, two experiments were conducted to investigate the effect of Mn source on Mn transport and the expression of a Mn transporter, divalent metal transporter 1 (DMT1), in the small intestine of broilers. In Expt 1, in situ ligated duodenal loops from Mn-deficient chicks (29-d-old) were perfused with solutions containing 0 -8·74 mmol Mn/l from either MnSO 4 , or one of two organic chelates of Mn and amino acids with moderate (OM) or strong (OS) chelation strength (Q f ) up to 30 min. In Expt 2, Mn-deficient intact broilers (14-d-old) were fed a control diet (12·45 mg Mn/kg) or the control diet supplemented with 100 mg Mn/kg as one of all Mn sources for 14 d. The uptake kinetics of Mn from different Mn sources in the ligated duodenal loops followed a saturable process as determined by regression analysis of concentration-dependent uptake rates. The maximum transport rate (J max ) and K m values, and DMT1 mRNA levels in the ligated duodenal loops were higher (P,0·01) for OM and OS than for MnSO 4 . DMT1 mRNA levels were much higher (P, 0·01) in the duodenum than in the jejunum and ileum. Both DMT1 mRNA levels in the duodenum and plasma Mn contents from the hepatic portal vein of intact chicks on day 14 post-feeding increased (P,0·05) in the following order: control , MnSO 4 , OM , OS. These results indicated that organic Mn sources with stronger Q f showed higher Mn transport and absorption, and DMT1 might be involved in the regulation of organic Mn transport in the proximal small intestine of broilers.
To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (SEM 1)°C and high, 32 (SEM 1)°C) × 3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P > 0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P < 0·003) Mn content, and also tended (P = 0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P < 0·05) and a slight increase of malondialdehyde level (P = 0·06) were detected in breast muscle. Up-regulated (P < 0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P < 0·0001), heart MnSOD and CuZnSOD activities (P < 0·01) and breast muscle MnSOD protein levels (P < 0·05), and lower (P < 0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P < 0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.Key words: Broiler breeders: Manganese: Heat stress: Antioxidant status: Heat-shock proteins/factorsThe effect of heat stress on productive performance has been extensively studied in poultry, especially in high-producing hens (1)(2)(3)(4) . High environmental temperature negatively influences the performance of laying commercial hens (1,2) and broiler breeders (3,4) by reducing feed intake, egg production and eggshell quality. In addition to altered productive performance, heat stress can also disturb the redox balance and induce oxidative stress, with the production of reactive oxygen species (ROS), in broiler breeders (5) and commercial hens (6) . Although substantial attention has been paid to the roles of antioxidant trace minerals (Se, Zn) in minimising the harmful effect of heat stress in broilers (7) and commercial laying hens (8) , the role of Mn in stress reduction has not been well studied. Mn is a crucial component of the metalloenzyme manganese superoxide dismutase (MnSOD) (9) , which has a key role in the detoxification of superoxide free radicals. A series of studies in our laboratory...
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