mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris

Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease.Aberrant mTOR pathway activity is involved in many autoimmun...     

One-lung ventilation patients: Clinical context of administration of different doses of dexmedetomidine

BackgroundOpen and endoscopic thoracic surgeries improve surgical exposure by One-lung ventilation (OLV). The aim of this study was to investigate the effects of different doses of dexmedetomidine on inflammatory response, oxidative stress, cerebral tissue oxygen saturation (SctO2) and intrapulmonary shunt in patients undergoing one-lung ventilation (OLV).MethodsSeventy-five patients undergoing open pulmonary lobectomy in our hospital from January 2016 to December 2017 were enrolled and randomly divided into high-dose dexmedetomidine group (group D1, 1 mg/kg, n=25), low-dose dexmedetomidine group (group D2, 0.5 mg/kg, n=25) and control group (group C, n=25). Then, arterial blood and internal jugular venous blood were taken before anesthesia induction (T0) and at 15 min after twolung ventilation (T1) and 5 min (T2) and 30 min (T3) after OLV for later use. Next, the changes in hemodynamic parameters [mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2)] of patients were observed in each group. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect serum inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)]. The changes in SctO2, arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt Qs/Qt (a measurement of pulmonary shunt: right-to-left shunt fraction) were observed. Additionally, the changes in lung function indicators like lung dynamic compliance (Cdyn) and airway peak pressure (P_peak) were determined.ResultsThere were no statistically significant differences in the MAP, HR and SpO2 among three groups at each observation time point (P>0.05). At T2 and T3, the levels of serum IL-6, TNF-α and IL-8 were obviously decreased in group D1 and D2 compared with those in group C (P<0.05), and the decreases in group D1 were overtly larger than those in group D2, and the decreases at T3 were markedly greater than those at T2 (P<0.05). In comparison with group C, group D1 and D2 had notably reduced levels of serum reactive oxygen species (ROS) and MDA (P<0.05) and remarkably increased SOD content (P<0.05) at T2 and T3, and the effects were markedly better in group D1 than those in group D2. Besides, they were significantly superior at T3 to those at T2 (P<0.05). The SctO2 in group D1 and D2 was evidently lowered at T2 and T3 compared with that at T0, and the decrease in group D1 was distinctly smaller than that in group D2 (P<0.05). The Qs/Qt was significantly lower in group D1 and D2 than that in group C at T2 and T3 (P<0.05), while the PaO2 content was notably raised (P<0.05), and the decrease and increase were significantly larger in group D1 than those in group D2, and they were obviously greater at T3 to those at T2 (P<0.05). At T0 and T1, no significant differences were detected in the Cdyn, Pplat and Ppeak among three groups. At T2 and T3, the Cdyn was significantly elevated, while the Pplat and Ppeak overtly declined (P<0.05), and group D1 had greater changes in comparison with group D2, and the changes were obviously more evident at T3 to those at T2 (P<0.05).ConclusionsDexmedetomidine effectively ameliorates inflammatory response and oxidative stress, lowers oxygenation, Qs/Qt and the decrease in SctO2 and improves lung function during OLV, with good efficacy.     

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.     

Molecular roots of degenerate specificity in syntenin's PDZ2 domain: reassessment of the PDZ recognition paradigm

Crystal structures of the PDZ2 domain of the scaffolding protein syntenin, both unbound and in complexes with peptides derived from C termini of IL5 receptor (alpha chain) and syndecan, reveal the molecular roots of syntenin's degenerate specificity. Three distinct binding sites (S(0), S(-1), and S(-2)), with affinities for hydrophobic side chains, function in a combinatorial way: S(-1) and S(-2) act together to bind syndecan, while S(0) and S(-1) are involved in the binding of IL5Ralpha. Neither mode of interaction is consistent with the prior classification scheme, which defined the IL5Ralpha interaction as class I (-S/T-X-phi) and the syndecan interaction as class II (-phi-X-phi). These results, in conjunction with other emerging structural data on PDZ domains, call for a revision of their classification and of the existing model of their mechanism.     

Effects of Aroclor 1254 on the expression of rat placental PRL-family genes

This study was performed to investigate the effects of Aroclor 1254 (A1254), a commercial polychlorinated biphenyl mixture, on the expression of rat placental prolactin (PRL) family genes and reproductive activity. Placental lactogen-Iv and -II, and prolactin-like protein-A and -C mRNA levels were significantly decreased in the placentas of A1254-treated rats in a dose-dependent manner. The mRNA levels of Pit-1alpha and beta isotypes, which are involved in the regulation of PRL family gene expression, were also decreased in the A1254-treated rat placenta. In the rat placental junctional zone, high-dose A1254 (25 mg/kg B.W.) treatment reduced the number of spongiotrophoblasts, cells in which the PRL family genes are expressed. Finally, maternal exposure to A1254 was shown to have significant toxic effects on reproductive activity, including embryonic and placental growth retardation, delay of parturition, and reduction of the number of pups per litter. The results of the present study indicated that A1254 has an inhibitory effect on PRL family, Pit-1alpha, and beta gene expression in the rat placenta, leading to significant toxic effects on reproductive activity in rats.     

Bronchial reactivity to histamine before and after sodium cromoglycate in bronchial asthma.

Out of 19 patients with extrinsic bronchial asthma challenged with 123 mug histamine acid phosphate by intravenous infusion only 13 responded with a fall in FEV1 of over 10% (mean 16%). Seventeen of these patients were given histamine 2 mg/ml by aerosol, and all responded with a mean decrease in FEV1 of 37.8%. When challenged with allergen extract by aerosol the mean decrease in FEV1 was 37.5%. After 40 mg sodium cromoglycate 15 of the 17 patients showed significant protection against allergen challenge with a mean decrease in FEV1 of only 23.6%. Inhalation of 40 mg sodium cromoglycate, however, failed to protect against histamine given by either the intravenous or aerosol route. Histamine given intravenously to asthmatic patients produces less of a bronchial response than when given by aerosol, even though the intravenous route produces many more systemic symptoms, such as flushing and throbbing headache. The protection of sodium cromoglycate against an allergen inhalation challenge is not due to histamine antagonsim.     

CSN1 N-terminal-dependent activity is required for Arabidopsis development but not for Rub1/Nedd8 deconjugation of cullins: a structure-function study of CSN1 subunit of COP9 signalosome

The COP9 signalosome (CSN) is a multifunctional protein complex essential for arabidopsis development. One of its functions is to promote Rub1/Nedd8 deconjugation from the cullin subunit of the Skp1-cullin-F-box ubiquitin ligase. Little is known about the specific role of its eight subunits in deneddylation or any of the physiological functions of CSN. In the absence of CSN1 (the fus6 mutant), arabidopsis CSN complex cannot assemble, which destabilizes multiple CSN subunits and contributes, together with the loss of CSN1, to the phenotype of fus6. To distinguish CSN1-specific functions, we attempted to rescue the complex formation with deletion or point-mutation forms of CSN1 expressed as transgenes in fus6. We show that the central domain of CSN1 is critical for complex assembly, whereas the C-terminal domain has a supporting role. By expressing the C231 fragment, which contains the structural information but lacks the presumed functional domain located at the N terminus, we have rescued the complex formation and restored the Rub1/Nedd8 deconjugation activity on cullins (fus6/C231). Nonetheless, fus6/C231 exhibits pleiotropic phenotype, including photomorphogenic defects and growth arrest at seedling stage. We conclude that CSN1 N-terminal domain is not required for the Rub1/Nedd8 deconjugation activity of cullins, but contributes to a significant aspect of CSN functions that are essential for plant development.     

Significance of seed culture methods on mycelial morphology and production of a novel anti-cancer anthraquinone by marine mangrove endophytic fungus Halorosellinia sp. (No. 1403)

The effects of seed culture methods on the mycelial morphology and production of a novel promising anti-cancer anthraquinone 1403C by marine mangrove saprophytic fungus Halorosellinia sp. (No. 1403) was investigated. Inoculums were prepared using different seed culture methods, i.e., mycelia obtained by grinding biomass that was harvested from baffled flask culture (M1); biomass harvested from baffled flask culture (M2); biomass obtained from unbaffled flask culture with glass beads (M3); biomass attained from unbaffled flask culture (Control). The corresponding fermentations using M1, M2 and M3 enhanced 1403C production by 243.5%, 194.8% and 70.2%, respectively, as compared to that using Control (0.33 ± 0.03 g/l). Interestingly, 1403C production increased with the increase of ratio of number of clumps to pellets. Maximum 1403C production from baffled flask cultures was 4.8-fold of that from unbaffled flask culture. Increasing shaking speed from 170 rpm to 260 rpm could highly improve 1403C production by 151.8%.