Arginine Supplementation Recovered the IFN-γ-Mediated Decrease in Milk Protein and Fat Synthesis by Inhibiting the GCN2/eIF2α Pathway, Which Induces Autophagy in Primary Bovine Mammary Epithelial Cells

Xia, Xiaojing,Che, Yanyi,Gao, Yuanyuan,Zhao, Shuang,Ao, Changjin,Yang, Hongjian,Liu, Juxiong,Liu, Guowen,Han, Wenyu,Wang, Yuping,Lei, Liancheng Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.5

During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mechanism. Interferon gamma ($IFN-{\gamma}$) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether $IFN-{\gamma}$ can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether $IFN-{\gamma}$ affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of $IFN-{\gamma}$ on milk synthesis in primary BMECs in vitro. The results showed that $IFN-{\gamma}$ significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following $IFN-{\gamma}$ treatment, and the inhibition of autophagy can improve milk protein and milk fat synthesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis confirmed that $IFN-{\gamma}$ mediated autophagy by depleting arginine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor $2{\alpha}$ ($eIF2{\alpha}$) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate $IFN-{\gamma}$-induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the $IFN-{\gamma}$-induced decrease in milk quality but also a useful therapeutic approach for $IFN-{\gamma}$-associated breast diseases in other animals and humans.

Structural and magnetic properties of M-type Sr0.1Ca0.4La0.5Fe12O19 ferrites: The effects of CoxFe3-xO4 in precursor

Xiubin Zhao,Shuang Zhang,Jinsong Li,Ailin Xia,Yujie Yang 한양대학교 청정에너지연구소 2023 Journal of Ceramic Processing Research Vol.24 No.1

M-type ferrite Sr0.1Ca0.4La0.5Fe12O19 magnetic powders doped with CoxFe3-xO4 (0 ≤ x ≤ 1.25) in precursors were prepared bya ceramics process. The structure of specimens were examined by using an X-ray diffractometer. Only the magnetoplumbitephase was found in the specimens with the cobalt content (x) from 0.25 to 1.25 in precursor. The specimens exhibited a typicalhexagonal M-type structure and the particles in specimens were uniformly distributed in size. The specimen with x=1.25 hadthe maximum saturation magnetization of 67.48 emu/g, while the residual magnetization and the coercivity of the specimenwith x=1.00 reached the maximum value of 31.83 emu/g and 1270 Oe, respectively.

Studies of the effects and mechanisms of ginsenoside Re and Rk₃ on myelosuppression induced by cyclophosphamide

Han, Jiahong,Xia, Jing,Zhang, Lianxue,Cai, Enbo,Zhao, Yan,Fei, Xuan,Jia, Xiaohuan,Yang, He,Liu, Shuangli The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside $Rk_3$ ($Rk_3$) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and $Rk_3$ on cyclophosphamide-induced myelosuppression. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Results: Both Re and $Rk_3$ could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of $G_0/G_1$ phase cells, and increase the proliferation index. Finally, Re and $Rk_3$ could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and $Rk_3$ could improve the hematopoietic function of myelosuppressed mice. The effect of $Rk_3$ was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and $Rk_3$ on myelosuppression.

Studies of the effects and mechanisms of ginsenoside Re and Rk₃ on myelosuppression induced by cyclophosphamide

Jiahong Han,Jing Xia,Lianxue Zhang,Enbo Cai,Yan Zhao,Xuan Fei,Xiaohuan Jia,He Yang,Shuangli Liu 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk₃ (Rk₃) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk₃ on cyclophosphamide-induced myelosuppression. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Results: Both Re and Rk₃ could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G₀/G₁ phase cells, and increase the proliferation index. Finally, Re and Rk₃ could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and Rk₃ could improve the hematopoietic function of myelosuppressed mice. The effect of Rk₃ was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk₃ on myelosuppression.

Arginine Supplementation Recovered the IFN-gamma-Mediated Decrease in Milk Protein and Fat Synthesis by Inhibiting the GCN2/eIF2alpha Pathway, Which Induces Autophagy in Primary Bovine Mammary Epithelial Cells

Liancheng Lei,Xiaojing Xia,Yanyi Che,Yuanyuan Gao,Shuang Zhao,Changjin Ao,Hongjian Yang,Juxiong Liu,Guo-wen Liu,Wenyu Han,Yuping Wang 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.5

During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mecha-nism. Interferon gamma (IFN-) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether IFN- can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether IFN- affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of IFN- on milk synthesis in primary BMECs in vitro. The results showed that IFN- significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following IFN- treatment, and the inhibition of autophagy can improve milk protein and milk fat syn-thesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis con-firmed that IFN- mediated autophagy by depleting argi-nine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor 2 (eIF2) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate IFN--induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the IFN--induced decrease in milk quality but also a useful therapeutic approach for IFN--associated breast diseases in other animals and humans.

PLCE1 Gene in Esophageal Cancer and Interaction with Environmental Factors

Guo, Li-Yan,Zhang, Shen,Suo, Zhen,Yang, Chang-Shuang,Zhao, Xia,Zhang, Guo-An,Hu, Die,Ji, Xing-Zhao,Zhai, Min Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Objective: To study the PLCE1 gene rs2274223 polymorphism with regard to esophageal cancer and its interaction with diet, lifestyle, psychological and environmental factors in Southwest Shandong province. Materials and Methods: A case series study (case-case) was conducted. Questionnaire data were collected and 3 ml-5ml venous blood was drawn for DNA extraction among the qualified research subjects. PLCE1 gene polymorphism was detected after PCR amplification of DNA. SPSS 13.0 software was used for statistical analysis of the data. Results: The three genotypes A/A, A/G and G/G PLCE1 gene rs2274223 was 31, 16 and 4 cases, accounting for 60.8%, 31.4%, 0.08% respectively. The difference of three genotypes (AA/GA/GG) proportion between negative and positive family history of patients was statistically significant, ${\chi}^2=6.213$, p=0.045. There was no statistically significant relationship between PLCE1 gene rs2274223 polymorphism and smoking, drinking, ${\chi}^2=0.119$, p=0.998, and ${\chi}^2=1.727$, p=0.786. There was no linkage of the three rs2274223 PLCE1 gene genotypes (AA/GA/GG) proportion with eating fried, pickled, hot, mildew, overnight, smoked, excitant food, eat speed, salt taste or not (p>0.05). or with living environment pollution and nine risk factors of occupational exposure (p>0.05). There was no statistically significant difference in TS scores between different genotype of rs2274223 PLCE1 gene. Conclusions: The PLCE1 rs2274223 polymorphism has a relationship with family history of esophageal cancer, but does not have any significant association with age, gender, smoking, alcohol drinking, food hygiene, eating habits, living around the environment and occupation in cases.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

Zhang Hai-Yang,Wu Feng-Yao,Li Xue-Song,Tu Ping-Hui,Zhang Cao-Xu,Yang Rui-Meng,Cui Ren-Jie,Wu Chen-Yang,Fang Ya,Yang Liu,Song Huai-Dong,Zhao Shuang-Xia 대한진단검사의학회 2024 Annals of Laboratory Medicine Vol.44 No.4

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.