Methionyl-methionine (Met-Met) is a functional dipeptide. Although the role of a dipeptide in milk protein synthesis is clearly established, whether Met-Met has an anti-inflammatory effect and a protective mechanism in bovine mammary epithelial cell (MAC-T) inflammation remains unknown. The purpose of this study was to determine the beneficial effects and underlying mechanisms of Met-Met on lipopolysaccharide (LPS)-induced MAC-T cell inflammation. RNA-seq, siRNA interference, and western blotting were performed to determine the anti-inflammatory mechanisms of Met-Met in the context of LPS exposure. Pretreatment with 2 mM Met-Met could reduce the increase in TNF-α (3.14 ± 0.55 vs 1.54 ± 0.26, P < 0.01), IL-1β (2.30 ± 0.21 vs 1.86 ± 0.11, P < 0.05), and IL-8 (3.49 ± 0.29 vs 0.62 ± 0.20, P < 0.01) after 1 μg/mL LPS exposure. RNA-seq analyses indicated that the overlapping genes were primarily enriched in the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), and IL-17 pathways. The suppression of NF-κB, P38, and JNK by Met-Met was mediated through the Janus kinase 2-signal transducers and activators of transcription 5 (JAK2-STAT5) pathway. Moreover, the Met-Met-mediated decrease in the LPS-induced activation of p-IκB, NF-κB, and JNK was reversed by knocking down JAK2. Collectively, Met-Met has beneficial effects on MAC-T cell inflammation by activating the JAK2-STAT5 pathway and then inhibiting the NF-κB and MAPK signaling pathways.
Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for, and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia. Now using the approach of in utero gene transfer we have discovered that Ulk4 plays a key modulatory role in corticogenesis. Knockdown of Ulk4 leads to significantly decreased cell proliferation in germinal zones and profound deficits in radial migration and neurite ramification. These abnormalities can be reversed successfully by Ulk4 gene supplementation. Ulk4 also regulated acetylation of α-tubulin, an important post-translational modification of microtubules. We conclude that Ulk4 plays an essential role in normal brain development and when defective, the risk of neurodevelopmental disorders such as schizophrenia is increased.
Sensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex. Eliminating sensory input to either hemisphere by unilateral transection of infraorbital nerve (ION) prevents target selection of callosal axons in contralateral cortex. Strikingly, blocking sensory input bilaterally, by simultaneously transecting both IONs, results in rescued callosal projection. In contrast, non-simultaneous bilateral ION transection has the same effect as unilateral transection. Similar results are obtained by lesion of whisker hair follicles. c-Fos-positive neurons in brain slices treated with KCl is decreased more in contralateral cortex with unilateral removal of sensory input, but decreased similarly in both cortices in mice with simultaneous bilateral removal of sensory input. Frequency of sEPSC of cortical neurons is also reduced in contralateral cortex with the unilateral removal of sensory input, but equally reduced on both sides with the bilateral removal of sensory input, suggesting that unbalanced bilateral sensory input might lead to mismatched neuronal activity between the two cortices and contribute to the formation of callosal projection. Our data demonstrate a critical role of balanced bilateral somatosensory input in the formation of callosal connections, and thus reveal a new role of sensory input in wiring brain circuits.
OBJECTIVE Epidermal stem cells (ESCs) can actively participate in wound healing and enhance reepithelialization. To establish ideal diabetes mellitus (DM) rat models and to investigate the expression of keratin 19 (K19), beta1-integrin, beta-catenin, and proliferating cell nuclear antigen (PCNA) in ESCs of DM rat model, then to study the potential mechanism of difficult recovering wounds of diabetic skin. METHODS Twenty male SD rats (weighing 250-300 g) were divided into DM group and normal control group randomly (n=10). The DM rat model was made by intraperitoneal injected 65 mg/kg streptozocin (STZ), the normal control group was not treated. At 4 weeks after injection, pancreatic tissue was harvested for HE staining in two groups. The ESCs isolated from full-thickness skins of the back of two group rats were cultured and identified. The 2nd passage of ESCs were obtained for immunocytochemical staining of K 19, beta1-integrin, beta-catenin, and PCNA. Meanwhile, the cell cycle were measured by flow cytometry. The cell colony formation rates were detected after 1 week. RESULTS The achievement ratio of DM rat model was 90% with good stability. HE staining showed that the number of islet cells significantly decreased with degeneration and necrosis in DM group; the structure of islet cell was clear without degeneration and necrosis in normal control group. The integral absorbance values of positive expression for K19, beta1-integrin, beta-catenin, and PCNA in ESCs of DM group (82.63 +/- 14.77, 21.59 +/- 4.71, 6.49 +/- 6.58, and 90.77 +/- 12.44, respectively) were significantly lower than those in the normal control group (151.24 +/- 42.83, 54.48 +/- 17.43, 116.39 +/- 9.26, and 110.62 +/- 20.67, respectively) (P < 0.01). The clone forming efficiency of ESCs in DM group (6.43% +/- 1.01%) was significantly lower than that in the normal control group (11.37% +/- 1.62%) (P < 0.01). Flow cytometry indicated that 88.89% of cultured ESCs in the DM group were in resting state/pre-DNA-synthetic gap (G0/G1), and the apoptosis rate was 3.98%; 91.50% in the normal control group and the apoptosis rate was 0. CONCLUSION The DM rat model can be effectively induced by intraperitoneal injected 65 mg/kg STZ. The decreased amount and the low proliferation and differentiation capacity of ESCs may be one of the important mechanisms of difficult recovering wounds of DM rats.
This study aimed at observing the anatomy traits,microstructure and ultrastructure of the testes of the ostrich chicks and investigating the distribution of neuropeptide Y(NPY)immunoreactivity positive substance.Light and transmission electron microscopical methods were used to observe the morphological structure of ostrich testes.The location of NPY in the testes of the ostrich chicks was studied with immunohistochemical method,SABC.The results of the present study were as follows:there was albuginea composed of tenacious connective tissue on the surface of the ostrich testes,but the connective tissue in the testes was not abundant,and there were not mediastinum testis and lobules of testis in ostrich testis.The diameter of the seminiferous tubule of ninety days ostrich was 85-90 μm.The seminiferous epithelium was composed of sustentacular cells and one or two layers spermatogenic cell.The spermatogenous cells began to cleavage and generation,and the phase of cleavage was saw obviously.The primary spermatocytes was bigger,but few and were smaller the nuclei.There were less mitochondria,free ribosome and endoplasmic reticulum in the intracytoplasm of the spermatogenous cells,and the nuclear pores were obvious.There were abundant cell organs in the intracytoplasm of the primary spermatocytes.The sustentacular cells contained more free ribosome,but other cell organs in them were not abundant.There was clear margin between the sustentacular cells and the spermatogenous cells.The shape of leydig cells was irregular,and the number of lipid droplet was major in the leydig cells.The results of immunohistochemistry test showed NPY immunoreactivity positive substance was distributed in the periphery of seminiferous tubule and small vessels of the testes,spermatocyte and interstitial tissue of testis.
Well Qian-9 is an appraisal well with total depth of 4296 m. it is located in Baimiao block of Zhongyuan oilfield. Wellhole collapse and shale shrinkage frequently take place in the well which result in pipe stucking and long section reaming. A polysulfonated potassium drilling fluid was firstly used, but downhole complexities were so serious because of the above problems that the hole had to been cemented and sidetrack drilled twice. MMH polyol drilling fluid was used alternately. Comparing with polysulfonated potassium drilling fluid, field using showed that MMH polyol drilling fluid exhibited good inhibition and slouging control, better lubricity and oil reservoir protection properties. Wellhole collapse and shale shrinkage have been prevented and the borehole maintained stable.
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