BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decr...BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.展开更多
Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this stu...Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.展开更多
目的评价抗CD25单克隆抗体对肾移植受者术后早期CD4+CD25high调节性T细胞(CD4+CD25 high Treg)的影响。方法2007年2-9月接受初次亲属活体供肾移植的受者41例,根据是否使用抗CD25单克隆抗体(商品名daclizumab)分为抗体组(21例)和对照组(2...目的评价抗CD25单克隆抗体对肾移植受者术后早期CD4+CD25high调节性T细胞(CD4+CD25 high Treg)的影响。方法2007年2-9月接受初次亲属活体供肾移植的受者41例,根据是否使用抗CD25单克隆抗体(商品名daclizumab)分为抗体组(21例)和对照组(20例)。其中抗体组在肾移植术前2h及术后第14天分别给予抗CD25单抗各50mg。在移植前及移植后第13、17、60天分别留取肝素抗凝外周血15ml。应用流式细胞仪测定两组受者外周血CD4+T细胞和CD4+CD25 high Treg比例的变化,半定量RT-PCR检测CD25 mRNA的表达变化。结果肾移植术后13、17、60d抗体组的CD25+T细胞占CD4+T细胞的比例(20%±8%、13%±7%、24%±9%)低于对照组(45%±6%、41%±5%、40%±6%),差异有统计学意义(P<0.05)。抗体组术后第17天CD4+CD25 high Treg占CD4+T细胞的比例为4.40%±0.26%,明显低于对照组(8.56%±0.36%,P<0.01);而术后13、60d抗体组CD4+CD25 high Treg所占比例分别为7.00%±0.47%、3.75%±0.19%,与对照组(分别为8.04%±0.32%、3.66%±0.31%)比较差异无统计学意义(P>0.05)。抗体组CD25 mRNA相对表达水平在给予第二次抗体前(术后第13天)为1.65±0.22,术后第17天为1.84±0.27,两者间差异无统计学意义(P>0.05)。对照组术后第17天CD25 mRNA相对表达水平为1.70±0.23,与抗体组比较差异无统计学意义(P>0.05)。结论两剂共100mg抗CD25单抗仅一过性地降低CD4+CD25 high Treg,不会影响其活化扩增,无损于术后早期的免疫耐受诱导及维持。展开更多
Background Cocaine addiction may involve complex neuroadaptations, including many changes of genes expression. Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced ge...Background Cocaine addiction may involve complex neuroadaptations, including many changes of genes expression. Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced gene expression change is poorly understood. To identify the changes in gene expression induced by repeated cocaine exposure through D3 dopamine receptors, we compared the expression of four molecules： Janus kinase 2 （Jak2）, g-aminobutanoic acid receptor subunit alpha 1 （GABAAα1）, glutamate receptor AMPA3 alpha 3 （GluR 3） and stromal cell derived factor 1 （SDF1）. These four have been implicated in mediating the actions of cocaine in the nucleus accumbens （NAc） and caudoputamen （CPu） in mice after acute and repeated cocaine exposure. Methods For the acute and repeated injections, the mice were divided into four groups： 30 mg/kg cocaine, nafadotride 0.5 mg/kg ＋ cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal group. The expression of Jak2, GABAAα1, GluR 3 and SDF1 were assayed by Western blot, quantitative real-time RT-PCR and immunohistochemistry. Results Twenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAAα1 decreased in cocaine group compared with basal line and further decreased in the cocaine ＋ nafadotride group and remained at basal level in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine group compared with base line. However, the levels of Jak2 increased in cocaine ＋ nafadotride group compared with cocaine group, while remained at basal level in nafadotride group. Conclusions GABAAα1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.展开更多
Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports tha...Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.展开更多
Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates s...Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and survival.In the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell lines.Methods:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6.Lentiviral vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 cells.The biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were analyzed.Results:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 cells.Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and asparaginase.These effects were reversed by an anti-IL-2Rαantibody.Conclusions:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rαexpression.IL-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.展开更多
In this study,we investigated the transcriptional spatio-temporal dynamics of the taste 1 receptor(T1R)gene family repertoire in seabream(Sparus aurata[sa]),during larval ontogeny and in adult tissues.In early larval ...In this study,we investigated the transcriptional spatio-temporal dynamics of the taste 1 receptor(T1R)gene family repertoire in seabream(Sparus aurata[sa]),during larval ontogeny and in adult tissues.In early larval development,sa T1R expression arises heterochronously,i.e.the extraoral taste-related perception in the gastrointestinal tract(GIT)anticipates first exogenous feeding(at 9 days post hatching[dph]),followed by the buccal/intraoral perception from 14 dph onwards,supporting the hypothesis that the early onset of the molecular machinery underlying sa T1R expression in the GIT is not induced by food but rather genetically hardwired.During adulthood,we characterized the expression patterns of sa T1R within specific tissues(n=4)distributed in oropharingeal,GIT and brain regions substantiating their functional versatility as chemosensory signaling players to a variety of biological functions beyond oral taste sensation.Further,we provided for the first time direct evidences in fish for m RNA coexpression of a subset of sa T1R genes(mostly sa T1R3,i.e.the common subunit of the heterodimeric T1R complexes for the detection of“sweet”and“umami”substances),with the selected gut peptides ghrelin(ghr),cholecystokinin(cck),hormone peptide yy(pyy)and proglucagon(pg).Each peptide defines the enteroendocrine cells(ECCs)identity,and establishes on morphological basis,a direct link for T1R chemosensing in the regulation of fish digestive processes.Finally,we analyzed the spatial gene expression patterns of 2 taste signaling components functionally homologous to the mammalian G(i)a subunit gustducin,namely sa G(i)a1 and sa G(i)a2,and demonstrated their co-localization with the sa T1R3in EECs,thus validating their direct involvement in taste-like transduction mechanisms of the fish GIT.In conclusion,data provide new insights in the evolutionary conservation of gut sensing in fish suggesting a conserved role for nutrient sensors modulating entero-endocrine secretion.展开更多
基金the Program for Changing Scholars and Innovative Research Team in University, No. IRT0848Youth Foundation of Sichuan Province Science & Technology Bureau, No. 08ZQ026-061
文摘BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.
文摘Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.
文摘目的评价抗CD25单克隆抗体对肾移植受者术后早期CD4+CD25high调节性T细胞(CD4+CD25 high Treg)的影响。方法2007年2-9月接受初次亲属活体供肾移植的受者41例,根据是否使用抗CD25单克隆抗体(商品名daclizumab)分为抗体组(21例)和对照组(20例)。其中抗体组在肾移植术前2h及术后第14天分别给予抗CD25单抗各50mg。在移植前及移植后第13、17、60天分别留取肝素抗凝外周血15ml。应用流式细胞仪测定两组受者外周血CD4+T细胞和CD4+CD25 high Treg比例的变化,半定量RT-PCR检测CD25 mRNA的表达变化。结果肾移植术后13、17、60d抗体组的CD25+T细胞占CD4+T细胞的比例(20%±8%、13%±7%、24%±9%)低于对照组(45%±6%、41%±5%、40%±6%),差异有统计学意义(P<0.05)。抗体组术后第17天CD4+CD25 high Treg占CD4+T细胞的比例为4.40%±0.26%,明显低于对照组(8.56%±0.36%,P<0.01);而术后13、60d抗体组CD4+CD25 high Treg所占比例分别为7.00%±0.47%、3.75%±0.19%,与对照组(分别为8.04%±0.32%、3.66%±0.31%)比较差异无统计学意义(P>0.05)。抗体组CD25 mRNA相对表达水平在给予第二次抗体前(术后第13天)为1.65±0.22,术后第17天为1.84±0.27,两者间差异无统计学意义(P>0.05)。对照组术后第17天CD25 mRNA相对表达水平为1.70±0.23,与抗体组比较差异无统计学意义(P>0.05)。结论两剂共100mg抗CD25单抗仅一过性地降低CD4+CD25 high Treg,不会影响其活化扩增,无损于术后早期的免疫耐受诱导及维持。
基金the grants from the Science Technology Research Project fo Guangdong Province[Mo.2005B50301010]the Natural Science Foundation of Guangdong Province[No 40204411 and.06024380]the Medical Science Research Foundation of Guangdong Province[No.A200537]
文摘Background Cocaine addiction may involve complex neuroadaptations, including many changes of genes expression. Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced gene expression change is poorly understood. To identify the changes in gene expression induced by repeated cocaine exposure through D3 dopamine receptors, we compared the expression of four molecules： Janus kinase 2 （Jak2）, g-aminobutanoic acid receptor subunit alpha 1 （GABAAα1）, glutamate receptor AMPA3 alpha 3 （GluR 3） and stromal cell derived factor 1 （SDF1）. These four have been implicated in mediating the actions of cocaine in the nucleus accumbens （NAc） and caudoputamen （CPu） in mice after acute and repeated cocaine exposure. Methods For the acute and repeated injections, the mice were divided into four groups： 30 mg/kg cocaine, nafadotride 0.5 mg/kg ＋ cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal group. The expression of Jak2, GABAAα1, GluR 3 and SDF1 were assayed by Western blot, quantitative real-time RT-PCR and immunohistochemistry. Results Twenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAAα1 decreased in cocaine group compared with basal line and further decreased in the cocaine ＋ nafadotride group and remained at basal level in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine group compared with base line. However, the levels of Jak2 increased in cocaine ＋ nafadotride group compared with cocaine group, while remained at basal level in nafadotride group. Conclusions GABAAα1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.
基金supported by Chongqing basic research and frontier exploration project(cstc2022ycjh-bgzxm0119,China)。
文摘Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.
基金the National Natural Science Foundation of China(81400159,81873450,81700196,81672686)Pearl River Nova Program of Guangzhou(201710010161)+1 种基金Sister Institution Net-work Fund of the MD Anderson Cancer Center(to Qingqing Cai)the Fundamental Research Funds for the Central Universities(17ykpy77).
文摘Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and survival.In the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell lines.Methods:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6.Lentiviral vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 cells.The biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were analyzed.Results:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 cells.Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and asparaginase.These effects were reversed by an anti-IL-2Rαantibody.Conclusions:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rαexpression.IL-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.
基金covered by the National Research Agency(AEI,Spain)(grant number:PID2019-103969RB-C33)to Jos e M.Cerd a-Reverter。
文摘In this study,we investigated the transcriptional spatio-temporal dynamics of the taste 1 receptor(T1R)gene family repertoire in seabream(Sparus aurata[sa]),during larval ontogeny and in adult tissues.In early larval development,sa T1R expression arises heterochronously,i.e.the extraoral taste-related perception in the gastrointestinal tract(GIT)anticipates first exogenous feeding(at 9 days post hatching[dph]),followed by the buccal/intraoral perception from 14 dph onwards,supporting the hypothesis that the early onset of the molecular machinery underlying sa T1R expression in the GIT is not induced by food but rather genetically hardwired.During adulthood,we characterized the expression patterns of sa T1R within specific tissues(n=4)distributed in oropharingeal,GIT and brain regions substantiating their functional versatility as chemosensory signaling players to a variety of biological functions beyond oral taste sensation.Further,we provided for the first time direct evidences in fish for m RNA coexpression of a subset of sa T1R genes(mostly sa T1R3,i.e.the common subunit of the heterodimeric T1R complexes for the detection of“sweet”and“umami”substances),with the selected gut peptides ghrelin(ghr),cholecystokinin(cck),hormone peptide yy(pyy)and proglucagon(pg).Each peptide defines the enteroendocrine cells(ECCs)identity,and establishes on morphological basis,a direct link for T1R chemosensing in the regulation of fish digestive processes.Finally,we analyzed the spatial gene expression patterns of 2 taste signaling components functionally homologous to the mammalian G(i)a subunit gustducin,namely sa G(i)a1 and sa G(i)a2,and demonstrated their co-localization with the sa T1R3in EECs,thus validating their direct involvement in taste-like transduction mechanisms of the fish GIT.In conclusion,data provide new insights in the evolutionary conservation of gut sensing in fish suggesting a conserved role for nutrient sensors modulating entero-endocrine secretion.
