Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle / Estudo comparativo da distribuição e expressão de fator-1α indutível por neuroglobina e hipóxia no telencéfalo de iaques e bovinos

The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.(AU)

O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.(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)

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)

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 on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle / Estudo comparativo da distribuição e expressão de fator-1α indutível por neuroglobina e hipóxia no telencéfalo de iaques e bovinos

The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.

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.

Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1 in the telencephalon of yak and cattle

Abstract The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1 in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1 expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1 showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1 expression was found higher in cattle than yak. The HIF-1 expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1 may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1 seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

Resumo O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1 nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1 no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1 mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1 foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1 em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1 pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1 parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.

Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle / Estudo comparativo da distribuição e expressão de fator-1 indutível por neuroglobina e hipóxia no telencéfalo de iaques e bovinos

Abstract The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

Resumo O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.

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.

PD1/PDL1 expression is associated with increased TIM3 expression and tumor-infiltrating T lymphocytes in fibroblastic tumors.

PURPOSE: The combined therapy of inhibiting T cell immunoglobulin domain and mucin domain 3 (TIM3) and programmed cell death 1/programmed death-ligand 1 (PD1/PDL1) has shown encouraging therapeutic effects in some solid tumors. However, the expression of PD1/PDL1 and TIM3 in fibroblastic tumors is ill defined, which has limited the application of these immune checkpoint inhibitors in such tumors. METHODS: Immunostaining of 68 tissue microarray cores of fibroblastic tumors, including intermediate dermatofibrosarcoma protuberans and malignant myxofibrosarcoma and adult-type fibrosarcoma, was used to determine the expression of PD1, PDL1 and TIM3, as well as their relationship with the accumulation of tumor-infiltrating T lymphocytes (TILs). RESULTS: Both PD1 and PDL1 expression was only observed in a small proportion of fibroblastic tumors, whereas TIM3 was expressed in almost all tumors. However, only the positive expression of PDL1 was related to tumors with high grade and staging. A considerable number of TILs, including CD4- and CD8A-positive T cells and a small group of FoxP3-positive T cells, was also observed in most tumors. The density of TIM3 was positively correlated with that of TILs. Furthermore, higher densities of TIM3, CD4, CD8A and FoxP3 were observed in PD1 and PDL1 double-positive fibroblastic tumors. CONCLUSIONS: This study indicates that TILs with high expression of TIM3 may contribute to immunosuppression in the tumor microenvironment of fibroblastic tumors. Patients with fibroblastic tumors with high expression of PD1/PDL1 and TIM3 may therefore benefit from combination therapy with PD1/PDL1 and TIM3 inhibitors.

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.

Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle.

The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

Effect of feeding grape seed Proanthocyanidin extract on production performance, metabolic and anti-oxidative status of dairy cattle / Efeito da alimentação do extrato de semente de uva Proanthocyanidin sobre o desempenho da produção e o status metabólico e antioxidante de gado leiteiro

Aims to investigate the effects of grape seed proanthocyanidin extract (GSPE) on production performance, metabolism, and anti-oxidative status of Holstein dairy cattle in early lactation. Forty-eight multiparous Holstein dairy cattle were assigned to four groups (CON, G20, G40 and G80) and supplied with 0, 20, 40, and 80mg GSPE/kg of body weight/day. G20 significantly increased milk yield compared with other groups. Milk protein and non-fat-solids were increased in G20, G40 and G80 groups compared with the control group only at the 7th day during the experiment. No significant difference was observed in milk fat and somatic cell count, nor on parameters of energy metabolism in blood, liver function and kidney function between the four groups. There was no significant difference in glutathione peroxidase, superoxide dismutase, total antioxidant capacity, and hydrogen peroxide between the groups; but the malondialdehyde content of G20 significantly increased at day 14 in comparison with CON, and tended to increase at the 28th day. In conclusion, feeding 20mg GSPE/kg of body weight/day was associated with a significant increase in milk yield without detrimental effects on liver or kidney function and with substantial energy metabolism and antioxidant parameters improvement in early lactation dairy cattle.(AU)

O presente trabalho visa investigar os efeitos do extrato de semente de uva Proanthocyanidin (GSPE) sobre o desempenho da produção, o metabolismo e o status antioxidante de gado leiteiro Holstein em lactação precoce. Quarenta e oito vacas leiteiras multíparas Holstein foram divididas em quatro grupos (CON, G20, G40 e G80) e receberam 0, 20, 40 e 80mg de GSPE/kg de peso corporal/dia, respectivamente. O G20 aumentou significativamente o rendimento do leite em comparação com os outros grupos. A proteína e os sólidos não gordurosos do leite foram aumentados nos grupos G20, G40 e G80 somente no sétimo dia durante a experiência. Não foi observada diferença significativa na gordura do leite e na contagem de células somáticas, bem como nos parâmetros de metabolismo energético no sangue, na função hepática e na função renal entre os grupos em relação ao grupo controle. Não houve diferença significativa na glutationa peroxidase, na dimutase de superóxido, na capacidade antioxidante total e no peróxido de hidrogênio entre os grupos, mas o conteúdo malondialdeído do G20 aumentou significativamente no dia 14 em comparação com o CON, e tendia a aumentar no dia 28. Em conclusão, a alimentação de 20mg de GSPE/kg de peso corporal/dia foi associada a um aumento significativo no rendimento do leite, sem efeitos nocivos sobre a função hepática ou a renal, com o metabolismo de energia substancial e a melhoria dos parâmetros antioxidantes de gado leiteiro no início da lactação.(AU)

Effect of feeding grape seed Proanthocyanidin extract on production performance, metabolic and anti-oxidative status of dairy cattle / Efeito da alimentação do extrato de semente de uva Proanthocyanidin sobre o desempenho da produção e o status metabólico e antioxidante de gado leiteiro

Aims to investigate the effects of grape seed proanthocyanidin extract (GSPE) on production performance, metabolism, and anti-oxidative status of Holstein dairy cattle in early lactation. Forty-eight multiparous Holstein dairy cattle were assigned to four groups (CON, G20, G40 and G80) and supplied with 0, 20, 40, and 80mg GSPE/kg of body weight/day. G20 significantly increased milk yield compared with other groups. Milk protein and non-fat-solids were increased in G20, G40 and G80 groups compared with the control group only at the 7th day during the experiment. No significant difference was observed in milk fat and somatic cell count, nor on parameters of energy metabolism in blood, liver function and kidney function between the four groups. There was no significant difference in glutathione peroxidase, superoxide dismutase, total antioxidant capacity, and hydrogen peroxide between the groups; but the malondialdehyde content of G20 significantly increased at day 14 in comparison with CON, and tended to increase at the 28th day. In conclusion, feeding 20mg GSPE/kg of body weight/day was associated with a significant increase in milk yield without detrimental effects on liver or kidney function and with substantial energy metabolism and antioxidant parameters improvement in early lactation dairy cattle.(AU)

O presente trabalho visa investigar os efeitos do extrato de semente de uva Proanthocyanidin (GSPE) sobre o desempenho da produção, o metabolismo e o status antioxidante de gado leiteiro Holstein em lactação precoce. Quarenta e oito vacas leiteiras multíparas Holstein foram divididas em quatro grupos (CON, G20, G40 e G80) e receberam 0, 20, 40 e 80mg de GSPE/kg de peso corporal/dia, respectivamente. O G20 aumentou significativamente o rendimento do leite em comparação com os outros grupos. A proteína e os sólidos não gordurosos do leite foram aumentados nos grupos G20, G40 e G80 somente no sétimo dia durante a experiência. Não foi observada diferença significativa na gordura do leite e na contagem de células somáticas, bem como nos parâmetros de metabolismo energético no sangue, na função hepática e na função renal entre os grupos em relação ao grupo controle. Não houve diferença significativa na glutationa peroxidase, na dimutase de superóxido, na capacidade antioxidante total e no peróxido de hidrogênio entre os grupos, mas o conteúdo malondialdeído do G20 aumentou significativamente no dia 14 em comparação com o CON, e tendia a aumentar no dia 28. Em conclusão, a alimentação de 20mg de GSPE/kg de peso corporal/dia foi associada a um aumento significativo no rendimento do leite, sem efeitos nocivos sobre a função hepática ou a renal, com o metabolismo de energia substancial e a melhoria dos parâmetros antioxidantes de gado leiteiro no início da lactação.(AU)

MNS, Duffy, and Kell blood groups among the Uygur population of Xinjiang, China.

Human blood groups are a significant resource for patients, leading to a fierce international competition in the screening of rare blood groups. Some rare blood group screening programs have been implemented in western countries and Japan, but not particularly in China. Recently, the genetic background of ABO and Rh blood groups for different ethnic groups or regions in China has been focused on increasingly. However, rare blood groups such as MN, Duffy, Kidd, MNS, and Diego are largely unexplored. No systematic reports exist concerning the polymorphisms and allele frequencies of rare blood groups in China's ethnic minorities such as Uygur and Kazak populations of Xinjiang, unlike those on the Han population. Therefore, this study aimed to investigate the allele frequencies of rare blood groups, namely, MNS, Duffy, Kell, Dombrock, Diego, Kidd, Scianna, Colton, and Lutheran in the Uygur population of Xinjiang Single specific primer-polymerase chain reaction was performed for genotyping and statistical analysis of 9 rare blood groups in 158 Uygur individuals. Allele frequencies were compared with distribution among other ethnic groups. Observed and expected values of genotype frequencies were compared using the chi-square test. Genotype frequencies obeyed the Hardy-Weinberg equilibrium (P > 0.5) and allele frequencies were stable. Of all subjects detected, 4 cases carried the rare phenotype S-s- of MNS blood group (frequency of 0.0253), and 1 case carried the phenotype Jka-b- (frequency of 0.0063). Frequencies of the four groups, MNS, Duffy, Dombrock, and Diego, in the Uygur population differed from those in other ethnic groups. Gene distribution of the Kell, Kidd, and Colton was similar to that in Tibetan and Han populations, though there were some discrepancies. Gene distribution of Scianna and Lutheran groups showed monomorphism similar to that in Tibetan and Han populations. These findings could contribute to the investigation of the origin, evolution, and hematology of Uygur population of Xinjiang and assist in screening of rare blood groups in ethnic minorities, meeting of clinical blood supply demands, and building of the national rare blood group library.

Proteomic modulation in breast tumors after metformin exposure: results from a "window of opportunity" trial.

PURPOSE: Reverse Phase Protein Array (RPPA) is a high-throughput antibody-based technique to assess cellular protein activity. The goal of this study was to assess protein marker changes by RPPA in tumor tissue from a pre-surgical metformin trial in women with operable breast cancer (BC). METHODS: In an open-label trial, metformin 1500-mg PO daily was administered prior to resection in 35 non-diabetic patients with stage 0-III BC, body mass index ≥25 kg/m2. For RPPA, formalin-fixed paraffin-embedded (FFPE) samples were probed with 160 antibodies. Paired and two-sample t-tests were performed (p ≤ 0.05). Multiple comparisons were adjusted for by fixing the false discovery rate at 25 %. We evaluated whether pre- and post-metformin changes of select markers by RPPA were identified by immunohistochemistry (IHC) in these samples. We also assessed for these changes by western blot in metformin-treated BC cell lines. RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416. Cyclin D1 change after metformin by IHC was not observed. In cell lines, reductions in JNKpT183 and BadpS112 were seen, with no change in Cyclin D1 or Raptor. CONCLUSIONS: These results suggest that metformin modulates apoptosis/cell cycle, cell signaling, and invasion/motility. These findings should be assessed in larger metformin trials. If confirmed, associations between these changes and BC clinical outcome should be evaluated. CLINICALTRIALS. GOV IDENTIFIER: NCT00930579.

Gene Expression Patterns of Geese Expression Patterns of L-FABP, Spot 14, OB and APO A1 Genes in Different Tissues of Overfed and Control Geese

Ten-week-old Langde geese in similar body weight were randomly selected, four for overfeeding and four for routinly feeding. The abundance of liver fatty acid-binding protein (L-FABP), thyroid hormone-responsive (THRSP or Spot 14), obese (OB), and apolipoprotein A1 (Apo A1) genes in goose were detected by quantitative RT-PCR. L-FABP was higher expressed in liver and intestine than other tissues, but no expression was detected in the pancreas or brain. The other three genes were widely expressed in different tissues, OB was higher expressed in pancreas and abdominal fat, Spot 14 and Apo A1 was higher expressed in sebum and abdominal fat. Spot 14 and Apo A1 genes were up-regulated in overfed goose livers compared with that in the control. Thus, Spot 14 and Apo A1 genes may play important roles in lipid metabolism in goose fat liver.(AU)

Gene Expression Patterns of Geese Expression Patterns of L-FABP, Spot 14, OB and APO A1 Genes in Different Tissues of Overfed and Control Geese

Ten-week-old Langde geese in similar body weight were randomly selected, four for overfeeding and four for routinly feeding. The abundance of liver fatty acid-binding protein (L-FABP), thyroid hormone-responsive (THRSP or Spot 14), obese (OB), and apolipoprotein A1 (Apo A1) genes in goose were detected by quantitative RT-PCR. L-FABP was higher expressed in liver and intestine than other tissues, but no expression was detected in the pancreas or brain. The other three genes were widely expressed in different tissues, OB was higher expressed in pancreas and abdominal fat, Spot 14 and Apo A1 was higher expressed in sebum and abdominal fat. Spot 14 and Apo A1 genes were up-regulated in overfed goose livers compared with that in the control. Thus, Spot 14 and Apo A1 genes may play important roles in lipid metabolism in goose fat liver.

Role of interleukin-4 genetic polymorphisms and environmental factors in the risk of asthma in children.

Asthma is an allergic disease characterized by hyperresponsiveness and chronic inflammation of the airway. The interleukin-4 (IL-4) gene and its single nucleotide polymorphisms are associated with asthma susceptibility in children. A case-control study was performed to evaluate the relationship between asthma risk and the IL-4 rs2243250 (589 C/T) and rs2070874 (107 T/C), and IL-4 receptor (IL-4R) rs1801275 (576 Q/R) polymorphisms in 317 childhood asthma patients and 351 healthy children as controls. Polymerase chain reaction amplification and sequencing was performed. The effects of interactions between the genes of interest and environmental factors were also analyzed. IL-4 rs2243250 and rs2070874 allele and genotype frequencies did not significantly differ between the asthma and control groups (P > 0.05), but those of IL-4R rs1801275 did (P < 0.05). The RR genotype and R allele of this IL-4R variant were significantly associated with asthma risk, with odds ratios (ORs; and 95% confidence intervals) of 2.97 (2.08-4.25) and 2.99 (2.32-3.85), respectively. Logistic regression analysis showed that the IL-4R 576 Q/R RR genotype demonstrated a positive interaction with environments associated with smoking or pets in its effect on asthma risk, with ORs of 2.18 (P = 0.02) and 2.29 (P = 0.01), respectively. Our results suggest that the IL-4R rs1801275 polymorphism is associated with childhood asthma, and the RR genotype confers a high risk of developing this condition. This variant exhibited positive interactions with environments in which smoking or pets were present in increasing the risk of childhood asthma.

Association between aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism and susceptibility to colorectal cancer: a meta-analysis.

Numerous studies have evaluated the association between Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene and colorectal cancer (CRC) risk. However, the specific association remains controversial. To assess the relationship between the ALDH2 Glu504Lys polymorphism and CRC, we conducted a comprehensive meta-analysis of five case-control studies comprising 1664 patients with CRC and 2777 controls. The results of this meta-analysis showed that the ALDH2 Glu504Lys polymorphism was associated with a significantly reduced risk of CRC [Lys/Lys vs Glu/Glu: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.58-1.54; Glu/Lys vs Glu/Glu: OR = 0.85, 95%CI = 0.75-0.97; dominant model: OR = 0.86, 95%CI = 0.76-0.98; recessive model: OR = 1.00, 95%CI = 0.62-1.61]. No significant heterogeneity or publication bias was observed in our meta-analysis. Based on the statistical data, our meta-analysis indicates that the ALDH2 Glu504Lys polymorphism is associated with reduced risk of developing CRC.

Influence of interleukin-18 gene polymorphisms on acute pancreatitis susceptibility in a Chinese population.

We investigate the relationship between IL-18 -607C/A and -137G/C genetic polymorphisms and development of acute pancreatitis in a Chinese population. A total of 153 patients were consecutively recruited from the First Affiliated Hospital of Chongqing Medical University between January 2013 and November 2014. Genotyping of IL-18 -607C/A and -137G/C variants was performed using the polymerase chain reaction-restriction fragment length polymorphism method. We observed a significant difference between acute pancreatitis patients and control subjects with respect to age (t = 2.15, P = 0.02), gender (chi-square = 3.95, P = 0.04), body mass index (t = 5.85, P < 0.001), and alcohol consumption (chi-square = 9.74, P = 0.002). Using chi-square tests, we found that the genotype distributions of IL-18 -607C/A (chi-square = 0.81, P = 0.67) and -137G/C (chi-square = 1.16, P = 0.56) polymorphisms did not differ between the acute pancreatitis and control groups. Genotype frequencies of these variants were consistent with Hardy-Weinberg equilibrium in both patient and control groups. In addition, logistic regression analysis failed to identify a significant association between these polymorphisms and acute pancreatitis risk. Our study firstly examined their association in a Chinese population, and we suggest that the IL-18 -607C/A and -137G/ C polymorphisms do not influence susceptibility to acute pancreatitis in the Chinese population studied in the present study.