Influence of mesenchymal stem cells on respiratory distress syndrome in newborn swines via the JAK-STAT signaling pathway.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) threatens humans' health worldwide, causing huge labor and economic cost investment. This study aims to explore whether mesenchymal stem cells (MSCs) affect RDS in newborn swines via the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway by the establishment of the model of the disease. MATERIALS AND METHODS: The phosphorylation of the JAK-STAT signal transduction proteins was first detected via Western blotting to verify the regulatory effect of MSCs on RDS in newborn swines through the JAK-STAT signaling pathway. Then, the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was utilized to analyze the influences of the injection of MSCs into the blood of newborn model RDS swines on inflammatory factors in vivo. To further demonstrate the signal transduction function put forwarded, the RT-PCR and enzyme-linked immunosorbent assay (ELISA) were adopted to analyze the influences of the JAK-STAT signaling pathway inhibitor on the expression of the signature proteins of RDS in newborn swines and the changes in the inflammatory factors. RESULTS: MSCs induced the phosphorylation of JAK and STAT, and they activated the JAK-STAT signal transduction of RDS in newborn swines. Compared with those in normal saline group, the interleukin (IL)-2, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) expression levels in MSC group were increased, namely, MSCs substantially promoted their expression levels (p<0.05), but those of IL-10 and IL-13 were significantly decreased (p<0.05). CONCLUSIONS: The inhibitor of the JAK-STAT signaling pathway can suppress the therapeutic effect of MSCs on RDS in newborn swines.

The effect of dexmedetomidine on expressions of inflammatory factors in patients with radical resection of gastric cancer.

OBJECTIVE: To investigate the effect of dexmedetomidine on the expressions of inflammatory factors, T-lymphocyte subgroups and nuclear factor kappa-B (NF-κB) in peripheral blood monocytes in the perioperative period of radical resection of gastric cancer. PATIENTS AND METHODS: We selected 74 patients who were admitted to our hospital for radical resection of gastric cancer between January 2012 and October 2015. All patients were randomly divided into the dexmedetomidine group and the control group. Within 15 min before anesthesia induction, patients in the dexmedetomidine group received the intravenous injection of dexmedetomidine, while the same volume saline in the control group. During the operation, the initial dosage in the dexmedetomidine group was set as 1 µg/kg followed by 0.2 µg/kg•h intravenous injection to the end of operation. Three time points were selected: 15 min before anesthesia induction (T0), 1 h before the end of operation (T1) and 24 h after operation (T2). At these time points, we detected the levels of serum inflammatory factors using enzyme-linked immune sorbent assay (ELISA), immunoturbidimetry, and flow cytometer, respectively. RESULTS: The levels of IL-1ß, IL-6, TNF-α, NF-κB and CRP at T1 and T2 were significantly elevated compared with the levels at T0, and the amplitude of elevation in the control group was significantly larger than that in the dexmedetomidine group. The expression levels of T-lymphocyte subgroup in patients in both groups were decreased at T1 (compared with the levels at T0), and the decreasing extent of the ratio of CD4+ to CD8+ in the control group was significantly larger than that in the dexmedetomidine group. Meanwhile, we found that the percentages of CD3+ and CD4+ at T1 and T2 in the control group were significantly lower than those in the dexmedetomidine group. CONCLUSIONS: Dexmedetomidine can effectively reduce the release of inflammatory factors in patients that received the radical resection of gastric cancer, and the anti-inflammation effect may be exerted through downregulating the expression of NF-κB. Besides, dexmedetomidine can also alleviate the reduction in subgroups of CD3+ and CD4+, thereby ameliorating the impaired immune functions.

Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review.

OBJECTIVE: This study reviews the available data from randomized controlled trials on efficacy and safety of LCI699, a novel inhibitor of aldosterone synthase, as treatment of hypertension. MATERIALS AND METHODS: We performed a meta-analysis of phase II randomized, controlled trials comparing the efficacy/safety of LCI699 with placebo in hypertension patients. For this purpose, PubMed, Embase, Cochrane Library database, ISI-Science Citation Index, and the Chinese Biomedicine Literature Database were searched until August 2013. The available data on mean sitting systolic blood pressure (MSSBP), mean sitting diastolic blood pressure (MSDBP), adverse effects, renin-angiotensin-aldosterone system biomarkers (RAASB) and adrenocorticotropic hormone-stimulated cortisol concentration (AHSC) were collected. All data were analyzed using Review Manager, version 5.2. RESULTS: The present study finally included three randomized controlled trials, comprising of 623 patients in total. The daily use of ≥ 1 mg LCI699 was associated with a significant reduction of MSSBP (Weighted mean difference/WMD = -8.80, 95% CI: -11.31 to -5.68, p < 0.00001, I2 = 0%) and MSDBP (WMD = -4.94, 95% CI: -7.49 to -2.40, p = 0.00001, I2 = 9%). Adverse reactions occurred in 73 of the 139 patients (52.51%) treated with LCI699 and in 34 of the 63 patients (53.96%) treated with placebo. Pooled meta-analysis showed that the use of LCI699 was associated with no increased risk of side effects compared with placebo (RR = 0.90; 95% CI: 0.68 to 1.18, p = 0.43, I2 = 0%). Suppression of plasma aldosterone was measured at all doses of LCI699 treatment groups. LCI699 suppressed the ACTH-stimulated cortisol response in a dose- and time-dependent manner. CONCLUSIONS: Current evidence indicates that the novel aldosterone inhibitor LCI699 is an effective and well-tolerated antihypertensive agent that lowers plasma aldosterone concentration and produces a mild ACTH-stimulated cortisol response suppressive effect.

Molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii in China between 2007 and 2013 using multilocus sequence typing and the DiversiLab system.

The purpose of this study was to investigate the molecular characteristics of 83 clinical Cryptococcus neoformans/C. gattii species complex isolated in Beijing, China, between 2007 and 2013. Restriction fragment length polymorphism of the gene URA5 (URA5-RFLP), multilocus sequence typing (MLST), and automated repetitive polymerase chain reaction (rep-PCR; DiversiLab system) were performed to genotype these cryptococcal isolates. There was an excellent correlation amongst the three methods; however, PU157 was assigned as VNII according to URA5-RFLP, while it was classified as VNI by the DiversiLab system analysis. PU157 was finally identified as VNB by seven-locus MLST analysis. Moreover, though AD hybrids could not be processed by MLST, ideal results could be obtained by the DiversiLab system. The genotype VNI accounted for 95.2% (79/83) of isolates. Besides one strain of VNB, VNIII, and VGI each, a strain of VGII was detected in our study, which was isolated from a patient from the temperate region in North China. In addition, the most common MLST sequence type (ST) was ST5, accounting for 91.6% (76/83), followed by ST31, ST63, ST182, ST295, ST296, and ST332. ST295, ST296, and ST332 were new STs. Except for isolate PU157 (VNB), identical results were obtained quickly and accurately through the DiversiLab system compared to MLST and URA5-RFLP. The discovery of VNB and VGII in the temperate climate regions of China suggested that the population structure of C. neoformans and C. gattii should be explored more extensively. Our results also showed that the DiversiLab system can be used in the genotyping of C. neoformans and C. gattii.

An early Cambrian agglutinated tubular lophophorate with brachiopod characters.

The morphological disparity of lophotrochozoan phyla makes it difficult to predict the morphology of the last common ancestor. Only fossils of stem groups can help discover the morphological transitions that occurred along the roots of these phyla. Here, we describe a tubular fossil Yuganotheca elegans gen. et sp. nov. from the Cambrian (Stage 3) Chengjiang Lagerstätte (Yunnan, China) that exhibits an unusual combination of phoronid, brachiopod and tommotiid (Cambrian problematica) characters, notably a pair of agglutinated valves, enclosing a horseshoe-shaped lophophore, supported by a lower bipartite tubular attachment structure with a long pedicle with coelomic space. The terminal bulb of the pedicle provided anchorage in soft sediment. The discovery has important implications for the early evolution of lophotrochozoans, suggesting rooting of brachiopods into the sessile lophotrochozoans and the origination of their bivalved bauplan preceding the biomineralization of shell valves in crown brachiopods.

Extratemporal abnormalities of brain parenchyma in young adults with temporal lobe epilepsy: a diffusion tensor imaging study.

AIM: To examine extratemporal abnormalities of the cerebral parenchyma in young adult temporal lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI). MATERIALS AND METHODS: The study comprised 20 adults with unilateral TLE and 20 controls. The fractional anisotropy (FA), apparent diffusion coefficient (ADC), parallel eigenvalue (λ∥), and perpendicular eigenvalue (λ⊥) were calculated in the regions of interest (ROIs) using a 3 T MRI system. ROIs included the anterior/posterior limb of the internal capsule (AIC/PIC), external capsule (EC), head of caudate nucleus (HCN), lenticular nucleus (LN), thalamus (TL), and genu/body/splenium of the corpus callosum (GCC/BCC/SCC). RESULTS: Compared to controls, TLE patients showed lower FA in all ROIs; higher ADC in bilateral ECs, HCNs, TLs, and BCC; lower λ∥ in the ipsilateral LN and bilateral AICs, TL, and GCC; and higher λ⊥ in all ROIs except the bilateral PICs. In TLE patients, the ipsilateral TL had decreased FA compared with the contralateral TL. Pearson correlation analysis revealed a negative correlation between the ADC of the GCC and the age at onset of epilepsy; the λ∥ of the ipsilateral PIC and age at onset of epilepsy; the λ⊥ of the contralateral AIC and duration of epilepsy, respectively; and a positive correlation between the ADC of the GCC and the duration of epilepsy and the λ⊥ of the GCC and the duration of epilepsy, respectively. CONCLUSION: The study revealed bilateral extratemporal abnormalities in young adult TLE patients compared with controls. In addition, TLE patients with younger age at onset or longer duration of epilepsy may have more serious extratemporal changes.

Diffusion tensor imaging and 1H-MRS study on radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy.

AIM: To investigate the metabolic characteristics of the temporal lobes following radiation therapy for nasopharyngeal carcinoma using diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H-MRS). MATERIALS AND METHODS: DTI and (1)H-MRS were performed in 48 patients after radiotherapy for nasopharyngeal carcinoma and in 24 healthy, age-matched controls. All patients and controls had normal findings on conventional MRI. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), three eigenvalues λ1, λ2, λ3, N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatinine (Cr), and Cho/Cr were measured in both temporal lobes. Patients were divided into three groups according to time after completion of radiotherapy: group 1, less than 6 months; group 2, 6-12 months; group 3, more than 12 months. Mean values for each parameter were compared using one-way analysis of variance (ANOVA). RESULTS: Mean FA in group 1 was significantly lower compared to group 3 and the control group (p < 0.05). Group-wise comparisons of apparent diffusion coefficient (ADC) values among all the groups were not significantly different. Eigenvalue λ1 was significantly lower in groups 1 and 3 compared to the control group (p < 0.05). NAA/Cho and NAA/Cr were significantly lower in each group compared to the control group (p < 0.01 for both). The decrease in NAA/Cho was greatest in group 1. There were no significant between-group differences regarding Cho/Cr. CONCLUSION: A combination of DTI and (1)H-MRS can be used to detect radiation-induced brain injury, in patients treated for nasopharyngeal carcinoma.

The metabolites of a mangrove endophytic fungus, Penicillium thomi.

The chemical constituents research of the fermentation of Penicillium thomi separated from the root of Bruguiera gymnorrhiza led to the isolation of a new compound, 4',5-dihydroxy-2,3-dimethoxy-4-(hydroxypropyl)-biphenyl (1) and 11 known compounds. The structures of isolated compounds were determined by spectroscopic and chemical analysis. Their cytotoxic effects against three human cancer cell lines (A549, HepG2 and HT29) were also investigated.

Gap junction channel activity in short-term cultured human detrusor myocyte cell pairs: gating and unitary conductances.

Several independent lines of investigation indicate that intercellular communication through gap junctions modulates bladder physiology and, moreover, that altered junctional communication may contribute to detrusor overactivity. However, as far as we are aware, there are still no direct recordings of gap junction-mediated intercellular currents between human or rat detrusor myocytes. Northern and Western blots were used to identify connexin expression in frozen human bladder tissue and short-term cultured human detrusor myocytes. Double whole cell patch (DWCP) recording revealed that human detrusor myocyte cell pairs were well coupled with an average junctional conductance of 6.5 +/- 4.6 nS (ranging from 0.1 to 15 nS, n = 22 cell pairs). Macroscopic gap junction channel currents in human detrusor myocytes exhibited voltage dependence similar to homotypic connexin43. The normalized transjunctional conductance-voltage (G(j)-V(j)) relationship was symmetrical and well described by a two-state Boltzmann relation (G(min) approximately 0.33, V(0) = 63.6 mV, Z = 0.117 or equal to 2.95 gating charges), suggestive of a bilateral voltage-gated mechanism. In symmetric 165 mM CsCl, the measured single-channel slope conductance was approximately 120 pS for the fully open channel and approximately 26 pS for the major substate. Occasionally, other subconductance states were also observed. The single-channel mean open time declined with increasing V(j), accounting for the V(j)-dependent decline of macroscopic junctional current. Qualitatively similar electrophysiological characteristics were observed in DWCP of freshly isolated rat detrusor myocytes. These data confirm and extend previous observations and are consistent with reports in other smooth muscle cells types in which Cx43-mediated intercellular communication has been identified.

Relation between the axial length and lenticular progressive myopia.

PURPOSE: To investigate the possible risk factors associated with lenticular progressive myopia and to compare the differences between patients with lenticular progressive myopias and senile cataracts. METHODS: We retrospectively reviewed cases that had been diagnosed as lenticular progressive myopia with a discrete nuclear sclerotic cataract and progressive myopic changes in one hospital from January 1998 to February 2003. A total of 47 eyes of 35 patients were enrolled in this study. In all, 32 eyes of 29 cases of common senile cataract receiving cataract extraction surgery during the study period were randomly chosen (every four cases in time sequence within a 2-month period by two ophthalmologists' clinic in 2002) as the control group. We compared the preoperative refraction status, keratometry (K-values) and axial lengths between these two groups. The possible ocular or systemic associating diseases were also investigated in the study group. RESULTS: In the lenticular progressive myopia group, the mean age at surgery (52.9+/-9.2 years) is younger than that in the senile cataract group (68.1+/-7.3 years). The mean axial length in the study group (25.68+/-1.93 mm) is statistically significant longer than that in the control group (22.97+/-0.83 mm) (P<0.0001). Besides, patients with lenticular progressive myopia had significantly lower mean K-values (43.25+/-1.42 diopters) than patients with senile cataracts (44.25+/-1.28 diopters) (P<0.01). There were no other ocular or systemic diseases closely associated with lenticular progressive myopia. CONCLUSIONS: Patients with nuclear cataract combined with lenticular progressive myopia have longer axial length than patients with senile cataract. The longer axial length may be one of the important risk factors predisposing to lenticular progressive myopia.

Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers.

PURPOSE: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentration-response curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 microM.) and levcromakalim (10 microM.) induced whole cell potassium currents that were blocked by glibenclamide (10 microM.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.

Ion Channels and Gap Junctions: Their Role in Erectile Physiology, Dysfunction, and Future Therapy.

A flurry of research and clinical activity during this past decade has documented that the tonicity and synchronicity of the corporal smooth muscle cells of the penis are major determinants of erectile capacity and function. Specifically, the effects of diverse and bifurcating intracellular signal transduction pathways on the activity of nonjunctional ion channels such as potassium (K(+)), calcium (Ca(2+)), and chloride (C(1-)) govern the former, whereas intercellular communication through gap junctions provides the anatomic substrate for the latter. Recent studies at the tissue, cellular, subcellular, and molecular levels have verified this supposition and provided important insight into how subtle alterations in the balance between contraction and relaxation of the corporal smooth muscle cells can predispose a man to erectile failure. This report reviews the available information concerning the participation of gap junctions and K(+), Ca(2+), and C(1-) channels in the erectile process and describes their importance as potential molecular targets for the future therapy of erectile dysfunction (ED). It is argued that a major goal should now be to proceed on at least two fronts simultaneously: (1) to capitalize on these new mechanistic insights by developing novel treatments for ED centered on the modulation of ion channel activity; and (2) simultaneously to take advantage of the unique therapeutic opportunities afforded by the presence and ubiquitous distribution of gap junction channels in the human corpora. One strategy that fulfils both criteria will be briefly reviewed, that is, gene therapy with the maxi-K(+) channel subtype.