Comparative study of the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the adult and young Yak Brain / Estudo comparativo da distribuição e expressão de neuroglobina e fator-1α indutível por hipóxia em adultos e jovens iaques (Yak Brain)

Background: The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim: The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method: The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results: Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion: This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.(AU)

Contexto: O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo: O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método: O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados: Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão: Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.(AU)

Comparative study of the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the adult and young Yak Brain / Estudo comparativo da distribuição e expressão de neuroglobina e fator-1α indutível por hipóxia em adultos e jovens iaques (Yak Brain)

Abstract Background The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.

Resumo Contexto O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.

Comparative study of the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the adult and young Yak Brain / Estudo comparativo da distribuição e expressão de neuroglobina e fator-1α indutível por hipóxia em adultos e jovens iaques (Yak Brain)

Background: The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim: The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method: The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results: Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion: This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.

Contexto: O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo: O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método: O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados: Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão: Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.

Comparative study of the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1 in the adult and young Yak Brain

Abstract Background The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1 (Hif-1) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results Ngb and Hif-1 were significantly (P 0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1 expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1 are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.

Resumo Contexto O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo O estudo examinou a expressão de neuroglobina (Ngb) e fator-1 indutível por hipóxia (Hif-1) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados Ngb e Hif-1 foram significativamente (P 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1 apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1 são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.

Identification of Avian Toll-Like Receptor 3 and 7 and Analysis of Gene Variation Sites

Toll-like receptors 3 and 7 (TLR3 and 7) mediate immune responses through the recognition of viral single-stranded RNA and double-stranded RNA and therefore play important roles in host defense. Differences in TLR3 or 7 may affect host resistance to RNA viral infection. To illuminate these differences, the partial coding sequence (CDS) of TLR3 and 7 genes were cloned and amplified from the Phasianus colchicus and Numida meleagris, total 64 avian species of TLR3 and 7 sequences were later analyzed. Based on the results, 315 non-synonymous mutation sites and 202 synonymous mutation sites were also observed in the avian TLR3, and 227 non-synonymous mutation sites and 174 synonymous mutation sites were observed in the avian TLR7. Among these sites, 44 and 45 sites were observed in functional regions of TLR3 and 7, used common variation of amino acids in most avian species. A number of these different sites appeared to affect the recognition and were also visualized. H59Y, E60K, G64R, E93K, L112S, K117E, N118K, R120H, V123M, L163F, R443Q, R459K, E460D, C485H, and F511L for TLR3, and I432V, M437V, and T732S for TLR7 were considered. It is possible that these sites bind to ligands and play crucial roles in viral recognition. These data indicated that the positive selection has occurred in the avian TLR3 and 7 genes.(AU)

Comparative study of the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the adult and young Yak Brain.

BACKGROUND: The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. AIM: The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. METHOD: The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. RESULTS: Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. CONCLUSION: This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.

Long noncoding RNA MGC27382 inhibits proliferation and metastasis of non-small cell lung cancer cells via down-regulating AKT/GSK3ß pathway.

PURPOSE: Persistent abnormal proliferation and long distant metastasis of tumors contribute to high mortality rate in non-small cell lung cancer (NSCLC) patients. Strategies that prevent NSCLC proliferation and/or metastasis have been studied but still need to be further explored. Numerous studies have proved the diversity functions of long noncoding RNAs (lncRNAs) exerted in cancer, including NSCLC. In this study, we aim to identify and investigate the role of novel lncRNAs in NSCLC progression. METHODS: RNA sequence data were retrieved from the Cancer Genome Atlas (TCGA), differentially expressed lncRNAs (DElncRNAs) were screened out based on the R language, then real-time PCR experiment was introduced to detect the DElncRNA expression levels. A series of experiments including MTT, cell cycle, transwell, and wound healing assays were employed to explore the effect of DElncRNA MGC27382 on cell proliferation and invasion ability. RESULTS: We detected that DElncRNA MGC27382 is down-regulated in NSCLC tissues and cells. Overexpression of MGC27382 prevented NSCLC cell proliferation via down-regulating cyclin D1 and cyclin E. Moreover, wound healing and transwell assays indicated that the ability of cell invasion and migration could be impaired when cells were treated with MGC27382 overexpression. Further studies demonstrated that MGC27382-mediated inhibition on NSCLC progression can be impaired by LY294002, which is a frequently used inhibitor of AKT/GSK3ß pathway. CONCLUSION: MGC27382 is down-regulated in NSCLC. It exerts an inhibitory role in NSCLC development through suppressing the AKT/GSK3ß pathway. Our results indicate that the lncRNA MGC27382 might be a tumor-suppressor gene in NSCLC. Overexpression of MGC27382 is thought to be a potential strategy for overcoming NSCLC progression.

Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition.

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.

miR-22 suppresses cell viability and EMT of ovarian cancer cells via NLRP3 and inhibits PI3K/AKT signaling pathway.

PURPOSE: miR-22 plays a great role in inhibiting cell growth, metastasis and enhanced cell apoptosis in several cancers. The purpose of this study was to investigate the functions of miR-22 in ovarian cancer. METHODS: The proliferative ability was measured using CCK-8 assay. The protein expression associated with EMT and PI3K/AKT signaling biomarkers were measured by western blot. Luciferase assay applied to measure the luciferase activity. Kaplan-Meier method was performed to evaluate the overall survival rate of ovarian cancers. RESULTS: miR-22 was low expressed and NLRP3 was overexpressed in ovarian cancer tissues and cells, and downregulation of miR-22 was associated with poor prognosis. The expression of NLRP3 had a negative correlation with miR-22 expression in ovarian cancer. miR-22 promoted cell viability and EMT through directly binding to the 3'-UTR of NLRP3 mRNA and inhibited PI3K/AKT signaling pathway. NLRP3 partially restored functions of miR-22 on cell proliferation and EMT in ovarian cancer. CONCLUSION: miR-22 impaired cell viability and EMT by NLRP3 and inhibited PI3K/AKT signaling pathway in ovarian cancer. The newly identified miR-22/NLRP3/PI3K/AKT axis provides novel insight into the pathogenesis of ovarian cancer.

Evaluation of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of breast cancer.

PURPOSE: To evaluate the clinical value of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of breast cancer (BC). METHODS: 129 patients with BC and 50 patients with benign breast lesions were selected. They were scanned by color Doppler ultrasound on the breast. The relative expression of miR-21 and miR-27a in plasma was detected by real-time fluorescence quantitative PCR. The clinical value of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of BC was analyzed retrospectively. RESULTS: Two-dimensional ultrasound images of BC showed irregular shape, unclear boundary, burr-like edge, uneven internal echo, weakened rear echo, microcalcification, aspect ratio > 1 and axillary lymph node metastasis. The grade of blood flow signal was improved, mainly in grade II and above, which was statistically different from that of benign control group (P < 0.001). The relative expression of plasma miR-21 and miR-27a in breast cancer group was significantly higher than that in benign control group (P < 0.001). The relative expressions of plasma miR-21 and miR-27a in breast cancer group were significantly correlated with histological grade, clinical stage, lymph node metastasis and postoperation. The relative expression levels of miR-21 and miR-27a in plasma of patients with low histological grade (grade III), high clinical stage (stage III, IV) and lymph node metastasis before operation were significantly higher than those in patients with high histological grade (grade I, II), low clinical stage (stage I, II) and no lymph node metastasis after operation (P < 0.01). The sensitivity, accuracy and negative predictive value of ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of BC were significantly higher than those of each single examination. CONCLUSIONS: Color Doppler ultrasound combined with plasma miR-21 and miR-27a can significantly improve the diagnostic efficiency of BC, which is beneficial to early diagnosis and early clinical intervention.

Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.

Mechanical Properties of Natural Fiber Reinforced Foamed Concrete.

The mechanical characterization of plain foamed concrete (PFC) and fiber-reinforced foamed concrete (FRFC) with a density of 700 kg/m3 was performed with compression and tension tests. FRFC was reinforced with the natural fiber henequen (untreated or alkaline-treated) at volume fractions of 0.5%, 1% and 1.5%. Polypropylene fiber reinforcement was also used as a reference. For all FRFCs, the inclusion of the fibers enhanced the compressive and tensile strengths and plastic behavior, which was attributed to the increase of specimen integrity. Under compressive loading, after the peak strength, there was no considerable loss in strength and a plateau-like regime was observed. Under tensile loading, the fibers significantly increased the tensile strength of the FRFCs and prevented a sudden failure of the specimens, which was in contrast to the brittle behavior of the PFC. The tensile behavior enhancement was higher when treated henequen fibers were used, which was attributed to the increase in the fiber-matrix bond produced by the alkaline treatment. The microscopic characterization showed that the inclusion of fibers did not modify the air-void size and its distribution. Higher energy absorption was observed for FRFCs when compared to the PFC, which was attributed to the enhanced toughness and ductility by the fibers. The results presented herein warrant further research of FRFC with natural henequen fibers for engineering applications.

PRDX2 plays an oncogenic role in esophageal squamous cell carcinoma via Wnt/ß-catenin and AKT pathways.

PURPOSE: To investigate the role of PRDX2 in esophageal carcinoma (ESCA). METHODS: The expression of PRDX2 was detected in ESCA tissues. And PRDX2 expression in two ESCA cell lines was knocked down. Cell proliferation, metastasis and invasion were detected in these cells. RESULTS: Here, we found that PRDX2 expression was significantly increased in ESCA tissues and was associated with a poor prognosis in ESCA patients. In addition, PRDX2 expression was significantly associated with pathological grading, infiltration degree and 5-year survival time in ESCA patients. Next, we knocked down PRDX2 expression by PRDX2-shRNA transfection in two ESCA cell lines, Eca-109 and TE-1. Proliferation analysis indicated that in vitro PRDX2 knockdown decreased growth and clone formation of ESCA cells. Scratch and transwell assays indicated that cell migration and invasion were significantly inhibited by PRDX2 knockdown. In addition, PRDX2 knockdown inhibited cell cycle of ESCA cells and down-regulated Cyclin D1-CDK4/6. Moreover, PRDX2 knockdown regulated proteins involved in mitochondrial-dependent apoptosis, including increased Bax and Caspase9/3 and decreased Bcl2. Mechanism investigation indicated that PRDX2 knockdown led to inactivation of Wnt/ß-catenin and AKT pathways. CONCLUSIONS: Our data suggest that PRDX2 may function as an oncogene in the development of ESCA via regulating Wnt/ß-catenin and AKT pathways. Our study fills a gap in the understanding of the role of PRDX2 in ESCA and provides a potential target for ESCA treatment.

Cost-effectiveness analysis of capecitabine plus bevacizumab versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer from Chinese societal perspective.

PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.

Cost-effectiveness of trifluridine/tipiracil (TAS102) for heavily pretreated metastatic gastric cancer.

BACKGROUND AND AIM: Trifluridine/tipiracil (TAS102), a novel oral cytotoxic chemotherapy, significantly improved overall survival compared with placebo in heavily pretreated advanced gastric cancer. This study aimed to evaluate the cost-effectiveness of TAS102 in the third-line or later treatment for this population from the US payer perspective. METHODS: A Markov model was developed to simulate advanced gastric cancer, including three health states: progression-free survival (PFS), progressive disease (PD) and death. Model inputs were derived from a randomised, double-blind, placebo-controlled, phase 3 trial (TAGS trial, NCT02500043). Utilities were extracted from public resources. Costs were calculated from an American payer perspective. Sensitivity analyses were conducted to explore the impact of uncertainty. RESULTS: From the US payer perspective, treatment with TAS102 for patients with heavily pretreated advanced gastric cancer was estimated to increase costs by $59,180 compared with the placebo, with a gain of 0.06 quality-adjusted life years (QALYs) for an incremental cost-effectiveness ratio (ICER) of $986,333 per QALY. The costs for progression-free survival of TAS102 group had the greatest impact on the ICERs, as well as the cost of TAS102. CONCLUSION: Trifluridine/tipiracil (TAS102) is not a cost-effective choice for patients with heavily pretreated metastatic gastric cancer from an American payer perspective.

Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/ß-catenin signaling pathway.

PURPOSE: Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. METHODS: This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. RESULTS: In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased ß-catenin expression in HCC and GC cells, it increased that in CRC cells. CONCLUSION: The lncRNA-CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/ß-catenin signaling pathways.

The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis.

BACKGROUND: Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. RESULTS: A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61-0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59-0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57-1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. CONCLUSION: Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.

Prognostic implication of EGFR mutation status and subtype in resected lung adenocarcinoma patients irrespective of therapy.

OBJECTIVE: This study aimed to investigate the pure prognostic role of epidermal growth factor receptor (EGFR) mutation status and subtype in lung adenocarcinoma patients irrespective of therapy. MATERIALS AND METHODS: We retrospectively enrolled 119 cases of completely resected pathological stage I lung adenocarcinoma patients who received no postoperative chemotherapy or tyrosine kinase inhibitors. EGFR gene mutations from 18 to 21 exons were tested for all the patients. Disease-free survival (DFS) and overall survival (OS) were compared between patients with different EGFR mutation status and subtype using Kaplan-Meier methods. RESULTS: EGFR mutations were detected in 54 (45.4%) patients including two common mutation subtypes: 32 in-frame deletion within exon 19 (19del) and 19 point mutation within exon 21 (L858R). The frequency of EGFR mutations was much greater for patients of non-smokers versus current or ever smokers (58.1 versus 24.4%, P = 0.000), and a little greater for females versus males (53.8 versus 35.2%, P = 0.042). The median follow-up duration was 43.5 months, and there were no differences on DFS (P = 0.461) and OS (P = 0.989) between patients with EGFR mutations and those without in univariate analysis. The patients harboring 19del mutation had a better DFS (P = 0.028) and OS (P = 0.001) than the patients harboring L858R mutation with significant statistical difference. CONCLUSIONS: This study suggests that there is no difference on survival between patients with EGFR mutations and those without, but the patients harboring EGFR 19del mutation have survival advantage compared to those harboring EGFR L858R mutation.

Detection of Snps in the Melanocortin 1-Receptor (MC1R) and Its Association with Shank Color Trait in Hs Chicken

The melanocortin 1 receptor (MC1R) gene plays a key role in controlling the deposition of melanin. In mammals, the MC1Rgene is regarded as a major candidate gene in the control of melanin formation. In domestic animals, the MC1R gene mainly controls the expression of coat, skin, and plumage color in mammals and birds. In order to breed chickens with dark-green shank faster, we screened the molecular markers for shank color in a HS chicken population by exploring the relationship between polymorphism of the MC1R gene and three different shank colors (light green, dark green and yellow). Two primer pairs for code region of the MC1R gene were designed in the basic of chicken genomic sequence. DNA sequencing was performed to detect the polymorphisms and PCR was used to amplify DNA fragment. Sequences analysis indicated that 7 SNPs were predominant the three HS chicken populations with different shank color, including g.18,287,945C>T, g.18,288,088T>C, g.18,288,150G>A, g.18,288,303A>G, g.18,288,512G>A, g.18,288,513T>C, and g.18,288,520A>C. Association analysis revealed that the dark-green shank population showed moderate polymorphism, whereas the light-green shank population showed low polymorphism among overall 7 SNPs and that SNP6 (g.18,288,513T>C) may be significantly associated with three different shank colors in HS chickens. The haplotype CTGGACA had the largest haplotype frequencies, accounting for 56.22%, and the haplotype combination H1H1 is mainly distributed in the dark-green shank population, and may be used as molecular maker for marker-assisted selection of shank color in HS chickens.(AU)

Genetic Diversity and Phyletic Evolution of Eleven Chinese Indigenous and Three Commercial Chicken Breeds by mtDNA Sequences

Chinese indigenous chicken breeds are geographically widespread, and a total of 116 indigenous chicken breeds are listed as Chinese national genetic resources. However, these indigenous chicken breeds are facing serious challenges as declining population and germplasm degeneration because lots of commercial chicken breeds had been introduced. In this study, the genetic variations of eleven Chinese indigenous chicken breeds of Sichuan province and three commercial chicken breeds were investigated based on the partial mitochondrial DNA D-loop of 487bp in length. 147 individuals from 14 breeds were examined and 34 haplotypes were observed. Genetic diversity analysis showed that the highest haplotype diversity level was found in Dahen Chicken (DH) population, while the Arbor Acres Chicken (WF) and Roman layer (RM) showed lower genetic diversity levels. The long-term artificial selection may lead to reduced nucleotide diversity. Genetic population differentiation analysis indicated that most of the variation (80.80%) was attributed to variations among breeds. Phylogenetic analysis revealed that these individuals were divided into four distinct genetic clades, including cluster A, B, C and D. Eighteen haplotypes were classified as cluster A, eight haplotypes were classified as cluster B, five haplotypes were classified as cluster C and three haplotypes were classified as cluster D. There was no breed-specific clade. Our study firstly identified the populations genetic structure of Chinese indigenous chickens and the most important commercial breeds in Sichuan province, though the genetic diversity of indigenous breeds did not suffer obvious decrease, but could be helpful for efficient artificial breeding selection and genetic resources conservation.(AU)