The amino acid sensor MetRS is required for methionine-induced milk protein synthesis in a domestic pigeon model.

This study was conducted to investigate whether methionyl-tRNA synthetase (MetRS) is a mediator of Met-induced crop milk protein synthesis via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signalling pathway in breeding pigeons. In Experiment 1, a total of 216 pairs of breeding pigeons were divided into 3 groups (control, Met-deficient, and Met-rescue groups). In Experiments 2 and 3, forty pairs of breeding pigeons from each experiment were allocated into 4 groups. The 2nd experiment included a control group and 3 MetRS inhibitor (REP8839) groups. The 3rd experiment included a Met-deficient group, Met-sufficient group, REP8839 + Met-deficient group, and REP8839 + Met-sufficient group. Experiment 1 showed that Met supplementation increased crop development, crop milk protein synthesis, the protein expression of MetRS and JAK2/STAT5 signalling pathway, and improved squab growth. Experiment 2 showed that crop development, crop milk protein synthesis, and the protein expression of MetRS and the JAK2/STAT5 signalling pathway were decreased, and squab growth was inhibited by the injection of 1.0 mg/kg BW REP8839, which was the selected dose for the 3rd experiment. These results showed that Met supplementation increased crop development, crop milk protein synthesis, and the expression of MetRS and JAK2/STAT5 signalling pathway and rescued squab growth after the injection of REP8839. Moreover, the Co-IP results showed that there was an interaction between MetRS and JAK2. Taken together, these findings indicate that MetRS mediates Met-induced crop milk protein synthesis via the JAK2/STAT5 signalling pathway, resulting in improved squab growth in breeding pigeons.

Effect of different cooking methods on saponin content and hematopoietic effects of Panax notoginseng-steamed chicken on mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng-steamed chicken (PNSC) is a medicinal food with ethnic characteristics developed by the Miao ethnic group in the southeast of Yunnan Province, China. PNSC has been eaten for hundreds of years, and its tonic effect has been widely recognized by the people. However, its cooking conditions and scientific connotation of its effect of toning blood and supplementing deficiency are also lack of in-depth analysis. AIM OF THE STUDY: To optimize the cooking conditions of Panax notoginseng-steamed chicken (PNSC) and to explore its anemia-improving effects. MATERIALS AND METHODS: The ratio of P. notoginseng (PN) to chicken and the steaming time were systematically altered, and the PNSC cooking conditions was optimized with the response surface method. By establishing animal models of postpartum blood-deficiency anemia, acute hemorrhagic anemia and myelosuppressive anemia, the blood replenishing effect of PNSC was explored, and the blood replenishing mechanism of PNSC on myelosuppressive anemia was revealed by immunoblotting analyses and histopathological sectioning. RESULTS: The optimal processing conditions included a ratio of chicken to P. notoginseng of 100:5 and a steaming time of 5.5 h. The amounts of P. notoginseng polysaccharides (PNPS), total protein and blood-enriching P. notoginseng saponins were 44.3 mg/g, 2.48% and 2.04%, respectively. Freeze-dried powder of P. notoginseng steamed chicken soup (FPSC) was found to promote the recovery of routine blood factors and organ indexes in the three models of anemia and to activate the JAK2-STAT5 signaling pathway, induce phosphorylation of JAK2 and STAT5 and normalize the secretion of hematopoietic regulators EPO, IL-3, and TNF-α. CONCLUSION: FPSC improves the symptoms of anemia in mice, and it plays a role in tonifying blood by activating the JAK2-STAT5 signaling pathway and altering the expression of hematopoiesis-related factors.

Proteomics reveals that Di Dang decoction can regulate the Jak2/Stat5 signaling pathway and inhibit apoptosis by reducing the oxidative stress response in rats with acute intracerebral hemorrhagic stroke.

ETHNOPHARMACOLOGICAL RELEVANCE: Di Dang decoction (DDD) is a prescription used for the treatment of cerebral hemorrhage. Its use is derived from the theory of typhoid fever, it has an obvious clinical effect and it has been used in the clinic for a long time. The results of early quantitative proteomics and targeted proteomics studies showed that the administration of high-dose DDD 7 days may regulate the expression of the proteins S100A8, S100A9, Col1a1 and Col1a2. The first 3 days after bleeding begins is the critical period for intervention, what occurs within approximately 3 days after AICH is unclear. AIM OF THE STUDY: To explore the effects of Di Dang decoction (DDD) on the Jak2/Stat5 signaling pathway and apoptosis-related gene expression in rats with acute hemorrhagic stroke via the oxidative stress response by proteomics to reveal its neuroprotective mechanism. MATERIALS AND METHODS: Ninety healthy Sprague-Dawley (SD) rats were randomly divided into the control, model, and low-, medium-, and high-dose DDD groups, with 18 rats in each group. An acute intracerebral hemorrhage (AICH) model was established by injecting autologous blood into the caudate nucleus. The low-, medium- and high-dose groups were intragastrically administered 0.15625 g/mL, 0.3125 g/mL and 0.625 g/mL DDD, respectively, for 1 or 3 days. The control and model groups were given the same amount of normal saline. Neurological deficits were evaluated by the modified neurological severity score (mNSS) test, brain water content was measured to assess brain tissue damage, and pathological changes in the lesion site were observed by hematoxylin and eosin (HE) staining. The cerebral cortex was selected for quantitative proteomics, and >1.2/1 and <1/1.2 were used as the thresholds for upregulated and downregulated proteins, respectively. KEGG pathway and Gene Ontology (GO) enrichment analyses of the differentially expressed proteins were conducted. The levels of the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were measured by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to assess p-Jak2, Jak2, p-Stat5, Stat5, Bax, Bcl-2, and Caspase-3 protein expression. RESULTS: Compared with the model group, the group treated with high-dose DDD for 3 days exhibited significant improvements in neurological defects, brain histopathology, and brain edema; reduced the level of MDA and significantly increased the levels of CAT and SOD; significantly decreased p-Jak2 and p-Stat5 protein expression and expression of the pro-apoptotic genes Bax and c-Caspase-3; and significantly increased expression of the anti-apoptotic gene Bcl-2 (all p＜0.05). CONCLUSIONS: High-dose DDD administration for 3 days reduces the oxidative stress response, regulates the Jak2/Stat5 signaling pathway and inhibits apoptosis to exert a neuroprotective effect in rats with acute hemorrhagic stroke.

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway.

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. METHODS: KM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. RESULTS: NMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. CONCLUSION: NMN may have a positive effect on relieving symptoms of AD.

Reducing PRLR expression and JAK2 activity results in an increase in BDNF expression and inhibits the apoptosis of CA3 hippocampal neurons in a chronic mild stress model of depression.

Patients suffering from depression most commonly present with symptoms associated with the autonomic nervous system. Despite the satisfactory results achieved following treatment with vagus nerve stimulation and drug treatment, recurrence is a common occurrence in many patients. As described in numerous studies, prolactin receptor (PRLR) has been identified as an anxiolytic and anti-depressant factor in depression. However, the effect of PRLR on chronic mild stress (CMS)-induced depression remains to be thoroughly demonstrated. Therefore, the present study was conducted on the effect of PRLR gene on brain derived neurotrophic factor (BDNF) expression and hippocampal neuron apoptosis through the establishment of CMS-induced depression mouse models, with aims of providing a new and effective therapeutic option for depression. Microarray-based analysis was initially used to retrieve depression-related expression dataset and PRLR-related signaling pathway. Lentiviral vectors overexpressing PRLR or expressing PRLR-specific shRNA were used to up- or down-regulated the expression of PRLR in mice. Subsequently, the effects of PRLR on hippocampal neurons and pyramidal cells in CA1 and CA3 regions, and ultrastructure in hippocampal region were evaluated. Serum BDNF level and the positive rate of cleaved-Caspase-3 in hippocampal CA3 region were determined. Next, the regulatory mechanism by which PRLR gene silencing influences hippocampal neuron apoptosis via the JAK2-STAT5 signaling pathway was detected. PRLR gene was assumed to participate in the development of depression by regulating the JAK-STAT signaling pathway. Our results found that the mice with CMS-induced depression exhibited locomotion activity and anhedonia. In addition, a decrease in the number of pyramidal cells was observed in the hippocampus while that of apoptotic cells was increased. In addition, serum BDNF level was increased, and the expression of Caspase-3 and Bax in hippocampal neurons and the JAK2-STAT5 signaling pathway was decreased in response to PRLR silencing, along with increased expression of BDNF and Bcl-2. From the aforementioned findings, we concluded that PRLR gene silencing results in the inhibition of hippocampal neuron apoptosis and alleviation of CMS-induced depression by inactivating the JAK2-STAT5 signaling pathway and elevating BDNF expression, providing a new insight for the treatment of depression.

Efecto de Estradiol y Testosterona sobre la activación de la vía JAK2/STAT5 inducida por hormona de crecimiento / Estradiol and Testosterone effect on the activation of the JAK2/STAT5 pathway induced by growth hormone

Abstract: Sex hormones play a major role during pubertal growth. Estradiol (E2) and testosterone (T) levels progressively increase during puberty and in the presence of growth hormone (GH), growth velocity increases. Understanding the interactions between sex hormones and GH, may optimize the treatment of pubertal children with growth disorders. The aim of our study was to investigate possible molecular mechanisms which might potentiate longitudinal growth during puberty due to E 2or T combined with GH. We evaluated the GH/JAK2/STAT5 signaling pathway in the human hepatoma cell line HEPG2. Our results suggest that sex hormones potentiate the GH signaling pathway in a dose dependent fashion. Relatively low concentrations of E 2associated with GH induce a substantial activation of the GH pathway, whereas relatively high concentrations of T associated with GH produce a similar effect. These findings are concordant with the physiology of the pubertal growth spurt, which is an early event in girls (when E 2 circulating levels are low), and a late event in boys (when T circulating levels are high).

Resumen: Las hormonas sexuales, modulan el crecimiento durante la pubertad. Los niveles de estradiol (E2) y testosterona (T) aumentan progresivamente durante la pubertad y en combinación con la hormona de crecimiento (GH), producen un incremento en la velocidad de crecimiento en este período conocido como el "estirón puberal". El estudio de la interacción entre las hormonas sexuales y la GH, es de gran importancia para optimizar el tratamiento de niños(as) con alteraciones del crecimiento durante la pubertad. El objetivo de nuestro estudio fue investigar los posibles mecanismos que podrían potenciar el crecimiento longitudinal durante la pubertad, en especial las interacciones entre E 2o T en combinación con GH. Se evaluó la activación de la vía de señalización GH/JAK2/STAT5 frente al estímulo combinado con estas hormonas en cultivos celulares de hepatoma humana HEPG2. Nuestros resultados sugieren que existe un efecto potenciador de las hormonas sexuales sobre la vía de señalización de GH. Observamos que concentraciones relativamente bajas de E2 junto con GH producen una clara activación de la vía de señalización para GH, mientras que concentraciones relativamente altas de T junto con GH producen una activación similar. Estos hallazgos son concordantes con la fisiología del estirón puberal, que es más precoz en niñas (cuando los niveles circulantes de E2 son bajos), y más tardíos en varones (cuando los niveles circulantes de T son altos).