Challenges and recent advances in MOF-based gas separation membranes.

Membrane-based gas separation, characterized by a small footprint, low energy consumption and no pollution, has gained widespread attention as an environmentally friendly alternative to traditional gas separation. Metal-organic-frameworks (MOFs) are considered to be one of the most promising membrane-based gas separation materials because of their large specific surface area and high porosity. One of the hottest studies at the moment is how to utilize the characteristics of MOFs to prepare higher performance gas separation membranes. This paper provides a review of gas separation membranes used in recent years. Firstly, the synthesis methods of MOFs and MOF membranes are briefly introduced. Then, methods to improve the membrane properties of MOFs are described in detail, and include applications of lamellar MOFs, ionic liquid (IL) spin coating, functionalization of MOFs, defect engineering and mixed fillers. In addition, the challenges of MOF-based gas separation membranes are presented, including pore size, environmental disturbances, plasticization, interfacial compatibility, and so on. Finally, based on the current development status of the MOF membranes, the development prospects of MOF gas separation membranes are discussed. It is hoped to provide reliable and complete ideas for researchers to prepare high-performance gas separation membranes in the future.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Angelica sinensis polysaccharide suppresses the Wnt/ß-catenin-mediated malignant biological behaviors of breast cancer cells via the miR-3187-3p/PCDH10 axis.

Breast cancer (BC) is one of the most common malignant tumors in women. Angelica sinensis polysaccharide (ASP) is one of the main components extracted from the traditional Chinese medicine Angelica sinensis. Research has shown that ASP affects the progression of various cancers by regulating miRNA expression. This study aimed to explore the specific molecular mechanism by which ASP regulates BC progression through miR-3187-3p. After the overexpression or knockdown of miR-3187-3p and PDCH10 in BC cells, the proliferation, migration, invasion, and phenotype of BC cells were evaluated after ASP treatment. Bioinformatics software was used to predict the target genes of miR-3187-3p, and luciferase gene reporter experiments reconfirmed the targeted binding relationship. Subcutaneous tumor formation experiments were conducted in nude mice after the injection of BC cells. Western blot and Ki-67 immunostaining were performed on the tumor tissues. The results indicate that ASP can significantly inhibit the proliferation, migration, and invasion of BC cells. ASP can inhibit the expression of miR-3187-3p in BC cells and upregulate the expression of PDCH10 by inhibiting miR-3187-3p. A regulatory relationship exists between miR-3187-3p and PDCH10. ASP can inhibit the expression of ß-catenin and phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß) proteins through miR-3187-3p/PDCH10 and prevent the occurrence of malignant biological behavior in BC. Overall, this study revealed the potential mechanism by which ASP inhibits the BC process. ASP mediates the Wnt/ß-catenin signaling pathway by affecting the miR-3187-3p/PDCH10 molecular axis, thereby inhibiting the proliferation, migration, invasion, and other malignant biological behaviors of BC cells.

Immunological characteristics of human umbilical cord mesenchymal stem cells after hepatogenic differentiation.

BACKGROUND: Acute liver failure is one of the most intractable clinical problems. The use of bioartificial livers may solve donor shortage problems. Human umbilical cord mesenchymal stem cells (hUCMSCs) are an excellent seed cell choice for artificial livers because they change their characteristics to resemble hepatocyte-like cells (HLCs) following artificial liver transplantation. OBJECTIVE: This study aimed to determine whether the immunological characteristics of hUCMSCs are changed after being transformed into hepatocyte-like cells. METHODS: HUCMSCs were isolated by the adherent method. The following hUCMSC surface markers were detected using flow cytometry: CD45, CD90, CD105, CD34, and octamer-binding transcription factor 4 (OCT-4). Functional detection of adipogenic differentiation was performed. The hUCMSCs were cultured in complete medium (control group) or induction medium (induction group), and flow cytometry was used to detect cell surface markers. Peritoneal lavage fluid was collected after intraperitoneal injection of 1 × 106 cells/mouse over 40 minutes. The leukocyte count, labeled CD45, CD3, CD4 and CD8 antibodies, and flow detection of T lymphocyte subsets were determined using the peritoneal lavage fluid. RESULTS: Using phenotypic and functional identification, hUCMSCs were successfully isolated using a two-step induction method. The surface markers of the hUCMSCs cells changed after HLC induction. In vivo immune results showed that hUCMSCs and HLsC induced leukocyte production. CONCLUSION: Hepatic induction of hUCMSCs changes their cell surface markers. Both HLCs and hUCMSCs cause leukocytosis in vivo, but the immune response induced by HLCs is slightly stronger.

Mitral valve repair with artificial chordae replacement in children: a single-center experience.

OBJECTIVES: To summarize the experience of mitral valve (MV) repair with artificial chordae replacement in children, and analyze early and intermediate outcomes. METHODS: From January 2011 to May 2019, all patients (< 18 years) who received MV repair with artificial chordae replacement were retrospectively reviewed. Freedom from MV reoperation, MV dysfunction, moderate or severe MR were estimated by the Kaplan-Meier curve and log-rank test. RESULTS: A total of 30 patients were included in this study. According to our definition, 15 patients had simple lesions and 15 patients had complex lesions. During 36 months' follow-up (range 3-97 months), two patients received MV reoperation and seven patients developed MV dysfunction, including six patients with moderate or severe MR and one patient with mitral stenosis. Freedom from MV reoperation at 1, 5 and 8 years were 100%, 91.3% and 91.3%, respectively. And freedom from MV dysfunction at 1, 3 and 5 year were 96.0%, 77.1% and 61.8%, respectively. Five-year freedom from MV dysfunction showed significant differences between patients with simple lesions and patients with complex lesions (100% vs 32.7%, log-rank P = 0.008), and between patients aged less than 12 years and patients aged more than 12 year (33.5% vs 90.0%, log-rank P = 0.025). CONCLUSION: The early and intermediate outcomes of mitral valve repair with artificial chordae replacement were acceptable in children, and the outcomes were optimal in patients with simple lesions, and patients aged more than 12 years.

Sex differences in depressive-like behaviour may relate to imbalance of microglia activation in the hippocampus.

As is reported, the incidence and prevalence of depression are higher in women than in men, but the cause of this sex difference remains elusive. Although recent studies implicated that over-activated microglia played a crucial role in depression, whether hippocampal microglia associates with the sex difference of depressive-like behaviours is intriguing. In the present study, both male and female mice were subjected to chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioural tests were performed to evaluate depressive-like phenotypes, while several microglia-related biomarkers and neurotrophic factor in hippocampi were detected to analyse sex difference. As a result, CUMS interfered with the body weight gain, sucrose preference and spontaneous activity in mice of both sexes. However, this effect tended to be more impressive in females. Generally, hippocampal microglia were activated regardless of sex, but the expressions of pro- and anti-inflammatory factors induced by CUMS were sex-specific. Chronic stress increased hippocampal iNOS and IL-1ß mRNA levels only in male mice, while upregulated TNF-α mRNA just in females. Meanwhile, the expressions of hippocampal IL-10, Arg-1 and IL-1ra were all downregulated in CUMS females rather than males. In addition, though the ratios of the pro- vs. anti-inflammatory cytokines elevated after the stress paradigm in both sexes, we noticed more remarkable trends in female mice regarding TNF-α/IL-10 and iNOS/Arg-1. This discovery suggested that females were inclined to be more pro-inflammatory after stress. Afterwards, we observed that the expressions of BDNF and its receptor TrkB in hippocampus decreased greater in female compared to male mice when facing stress stimulations. Furthermore, the depressive-like behaviours were correlated to BDNF mRNA quantities in both sex mice, and there was also a sex-specific relationship between BDNF and hippocampal microglia-related inflammatory biomarkers. Collectively, our study speculated that the imbalance of microglial pro- and anti-inflammatory states as well as the BDNF-TrkB-dependent pathway in hippocampus is involved in the depressive-like behaviours. The "microglia-neuroinflammation-BDNF" interconnection may be a fundamental mechanism for sex differences in depression.

Fr­HMGB1 and ds­HMGB1 activate the kynurenine pathway via different mechanisms in association with depressive­like behavior.

Our previous study reported that fully reduced high mobility group box 1 (fr­HMGB1) and disulfide HMGB1 (ds­HMGB1) induce depressive­like behavior; however, the underlying mechanisms remain unclear. In the present study, the induction of depression via the kynurenine pathway by different redox states of HMGB1 was investigated in vivo and in vitro. To evaluate the expression of enzymes of the kynurenine pathway, reverse transcription­quantitative PCR and western blot analyses were conducted. Additionally, cytokine levels were measured by ELISAs. Following intracerebroventricular injection of ds­ and fr­HMGB1, behavioral tests were performed, revealing the presentation of depressive­like behavior, and essential proteins in the kynurenine pathway were demonstrated to be upregulated at the mRNA level, suggesting that ds­ and fr­HMGB1 contributed to the development of this behavior via the kynurenine pathway. ds­HMGB1 directly activated the kynurenine pathway and cytokines such as tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß) in the hippocampal tissue. Conversely, fr­HMGB1 upregulated the aforementioned factors only following treatment with H2O2. These findings indicated that ds­HMGB1 induced depression in a manner associated with the kynurenine pathway, whereas oxidation of fr­HMGB1 evoked activation of the kynurenine pathway, resulting in depressive behavior.

Outcomes of different rehabilitative procedures in patients with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries.

OBJECTIVES: The objective of this study was to compare our clinical outcomes of the central shunt and the right ventricle-pulmonary artery (RV-PA) connection in patients with pulmonary atresia, ventricular septal defect and the major aortopulmonary collateral arteries. METHODS: From November 2009 to October 2017, a total of 157 consecutive patients with pulmonary atresia, ventricular septal defect, the major aortopulmonary collateral arteries and the hypoplastic PAs who underwent palliative surgery were included. Seventy patients underwent the central shunt (the central shunt group) and 87 patients underwent the RV-PA connection (the RV-PA group). Propensity score matching was used to create 2 cohorts with similar baseline characteristics: 56 central shunt patients were one-to-one-matched with 56 RV-PA connection patients. The early and late outcomes were compared. RESULTS: The median duration of follow-up was 18 months in the central shunt group and 22 months in the RV-PA group (P = 0.10). The probability of complete repair was significantly lower in the central shunt group as compared with the RV-PA group (P = 0.048). The Kaplan-Meier estimates of complete repair rates were 47.2 ± 10.0% after 3 years and 56.0 ± 11.6% after 5 years in the central shunt group, which were lower as compared with 62.3 ± 7.6% after 3 years and 74.5 ± 7.2% after 5 years in the RV-PA group. The increase in the mean McGoon ratio and the mean Nakata index were significantly lower in the central shunt group than those in the RV-PA group (0.57 ± 0.52 vs 1.02 ± 0.44, P = 0.036; 98.2 ± 35.1 mm2/m2 vs 176.9 ± 85.4 mm2/m2, P = 0.025, respectively). The in-hospital morbidity and mortality after complete repair were similar between 2 groups. CONCLUSIONS: Compared with the central shunt, the RV-PA connection appears to be a more effective palliative procedure to improve the probability of complete repair and PA growth in patients with pulmonary atresia, ventricular septal defect and the major aortopulmonary collateral arteries, in whom primary repair is not feasible.

Clemastine Alleviates Depressive-Like Behavior Through Reversing the Imbalance of Microglia-Related Pro-inflammatory State in Mouse Hippocampus.

Backgrounds: Abundant reports indicate that neuroinflammatory signaling contributes to behavioral complications associated with depression and may be related to treatment response. The glial cells, especially microglia and astrocytes in brain regions of hippocampus and medial prefrontal cortex (mPFC), are major components of CNS innate immunity. Moreover, purinergic receptor P2X, ligand-gated ion channel 7 (P2X7R) was recently reckoned as a pivotal regulator in central immune system. Besides, it was pointed out that clemastine, a first-generation histamine receptor H1 (HRH1) antagonist with considerable safety profile and pharmacological effect, may suppress immune activation through modulating P2X7R. Herein, we investigated the potential anti-neuroinflammatory effects of clemastine on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in a mouse model. Methods: Male BALB/c mice were subjected to CUMS for 4 weeks, some of them were injected with clemastine fumarate solution. After the stress procedure, behavioral tests including Sucrose Preference Tests (SPTs), Tail Suspension Tests (TSTs) and locomotor activities were performed to evaluate depressive-like phenotype. Subsequently, expression of cytokines and microglia-related inflammatory biomarkers were assessed. Results: In the present research, we found that clemastine significantly reversed both the declination of SPT percentage and the extension of TST immobility durations in depression mouse model without affecting locomotor activity. Also, we observed that clemastine regulated the imbalance of pro-inflammatory cytokines including interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) in the hippocampus and serum of depressive-like mice. Additionally, clemastine significantly suppressed microglial M1-like activation specifically in the hippocampus, and also improved hippocampal astrocytic loss. Furthermore, clemastine downregulated hippocampal P2X7R without interfering with the expression of HRH1. Conclusion: As a safe and efficient anti-allergic agent, clemastine could impressively alleviate stress-related depressive-like phenotype in mice. Further evidence supported that it was because of the potential function of clemastine in modulating the expression of P2X7 receptor possibly independent of HRH1, therefore suppressing the microglial M1-like activation and pro-inflammatory cytokines release in brain regions of hippocampus rather than mPFC.

Hippocampal Mrp8/14 signaling plays a critical role in the manifestation of depressive-like behaviors in mice.

BACKGROUND: Depression is one of the most common mental disorders characterized mainly by low mood and loss of interest or pleasure. About a third of patients with depression do not respond to classic antidepressant treatments. Recent evidence suggests that Mrp8/14 (myeloid-related protein 8/14) plays a crucial role in cognitive dysfunction and neuroinflammatory diseases, yet its role in mood regulation remains largely uninvestigated. In the present work, we explored the potential role of Mrp8/14 in the progression of depression. METHODS: After 4 weeks of chronic unpredictable mild stress (CUMS), depressive-like symptoms and Mrp8/14 were determined. To verify the effects of Mrp8/14 on depressive-like behaviors, the inhibitor TAK-242 and recombinant Mrp8/14 were used. Furthermore, the molecular mechanisms in Mrp8/14-induced behavioral and biological changes were examined in vivo and ex vivo. RESULTS: Four-week CUMS contributed to the development of depressive symptoms. Mrp8 and Mrp14 were upregulated in the hippocampus and serum after exposure to CUMS. Pharmacological inhibition of Mrp14 attenuated CUMS-induced TLR4/NF-κB signaling activation and depressive-like behaviors. Furthermore, central administration of recombinant Mrp8, Mrp14, and Mrp8/14 resulted in neuroinflammation and depressive-like behaviors. Mrp8/14-provoked proinflammatory effects and depressive-like behaviors were improved by pretreatment with a TLR4 inhibitor. Moreover, pharmacological inhibition of TLR4 reduced the release of nitric oxide and reactive oxygen species in Mrp8/14-activated BV2 microglia. CONCLUSIONS: These data suggest that the hippocampal Mrp8/14-TLR4-mediated neuroinflammation contributes to the development of depressive-like behaviors. Targeting the Mrp8/14 may be a novel promising antidepressant approach.

[Inflammatory mechanism of depression and its new strategy for diagnosis and treatment].

Depression is a major class of mental illness; owing to its high prevalence, high disability rate and heavy disease burden, it has become a stern and formidable global health problem. It is generally believed that the etiology of depression is multifactorial, which is related to gender differences, chronic stress, dietary behavior and drug abuse. At present, the exact pathophysiological mechanism of depression still remains unclear, but researchers across the globe put forward various hypotheses to interpret the possible access to this disease, including monoamine neurotransmitter disturbance, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, lack of neurotrophic factors and excessive pro-inflammatory cytokines. Based on the latest research evidence and the objective fact that traditional antidepressants may be ineffective in some particular patients, the "cytokine theory" tends to attract more and more attention recently. To date, researches on the role of cytokines in the pathogenesis of depression mainly focus on pro-inflammatory cytokines, especially categories including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). With the proceeding of researches from all over the world, a variety of novel molecules and mechanisms were postulated. This paper summarized a large amount of in vitro and in vivo research evidence, in order to review the current progress of the researches on pathophysiology of depression from the perspective of pro-inflammatory cytokines. Since the response rate of antidepressant therapy during present medical practice is unsatisfying, we suggest a new feasible diagnosis and treatment strategy, that is to distinguish the inflammatory status of patients with depression and take anti-inflammatory treatment into consideration. Totally, this novel strategy aims at modulating the conventional clinical protocol for treatment-resistant depressive patients and overcoming the limitation of insufficient antidepressant response possibly resulted from inflammation.

A non-catalytic vapor growth regime for organohalide perovskite nanowires using anodic aluminum oxide templates.

In this work, a novel and facile synthesis process to fabricate single crystalline organometal halide perovskite nanowires has been successfully developed. Nanowires were grown in a high density ordered array from metal nanoclusters inside anodic aluminum oxide templates using a non-catalytic chemical vapor deposition method. Specifically, perovskite NWs were grown as a result of the reaction between methylammonium iodide (MAI) and the Pb/Sn (Pb or Sn) metal in anodic aluminum oxide templates under optimal conditions. The characterization results show that there is a reaction zone at the interface between the perovskite material and metal, at the bottom of the anodic aluminum oxide nanochannels. In order to sustain perovskite NW growth, MAI molecules have to diffuse downward through the perovskite NWs to reach the reaction zone. In fact, the reaction is facilitated by the formation of an intermediate product of the metal iodide compound. This suggests that the Pb/Sn metal is converted to PbI2/SnI2 first and then perovskite NWs are formed as a result of the reaction between MAI and PbI2/SnI2 through a vapor-solid-solid process. The optical characterization results demonstrate that the as-synthesized NWs with an ultra-high nanostructure density can serve as ideal candidates for optoelectronic devices, such as solar cells, light-emitting didoes, photodetectors, etc. And the reported growth approach here is highly versatile combining the merits of excellent controllability, cost-effectiveness and tunability on material composition and physical properties.

Micro RNA-98 suppresses interleukin-10 in peripheral B cells in patient post-cardio transplantation.

The immune tolerance to the transplant heart survival is critical. Regulatory B cells are one of the major immune regulatory cell populations in the immune tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. In this study, the peripheral blood samples were collected from patients before and after heart transplantation. The expression of miR-98 and IL-10 in B cells was assessed by real time RT-PCR. An allograft heart transplantation mouse model was developed. We observed that after heart transplantation, the frequency of peripheral B10 cell and the IL-10 mRNA levels in peripheral B cells were significantly decreased, the levels of miR-98 were increased in peripheral B cells and the serum levels of cortisol were increased in the patients. Treating naive B cells with cortisol in the culture suppressed the expression of IL-10 in B cells, which was abolished by knocking down the miR-98 gene. Administration with anti-miR-98, or cortisol inhibitor, or adoptive transfer with B10 cells, significantly enhanced the survival rate and time of mice received allograft heart transplantation. In conclusion, the enhancement of serum cortisol affects the immune tolerant feature of B cells, which can be attenuated by anti-miR-98-carrying liposomes.

Ds-HMGB1 and fr-HMGB induce depressive behavior through neuroinflammation in contrast to nonoxid-HMGB1.

High mobility group box 1 (HMGB1) has been implicated as a key factor in several neuroinflammatory conditions. Our previous study suggested that the release of central HMGB1 acts as a late-phase mediator in lipopolysaccharide (LPS)-induced depression. Recent findings indicate that the redox state of HMGB1 is a critical determinant of its immunomodulatory properties. Here, we aimed to investigate the potential mechanisms that link the redox states of HMGB1 to depression in mice. Distinct redox forms of recombinant HMGB1 (rHMGB1) were used that included fully reduced HMGB (fr-HMGB1), which acted as a chemokine, and disulfide-HMGB1 (ds-HMGB1), which possessed cytokine activity. Fr-HMGB1 in vivo was partially oxidized into ds-HMGB1; thus, the mutant protein non-oxidizable chemokine-HMGB (nonoxid-HMGB1) was applied. Concurrent with depressive behavior induced by four-week stress exposure, the HMGB1 concentrations in the serum and cerebral cortex substantially increased. Therefore, a single dose of rHMGB1 (200ng/5µl/mice) or vehicle was administered to mice via intracerebroventricular (i.c.v.) injection. The receptor inhibitors of TLR4/RAGE/CXCR4 (TAK-242/FPS-ZM1/AMD3100) (3mg/kg) were intraperitoneally injected 30min prior to rHMGB1 treatment. Depressive-like behavior was measured 20h post i.c.v. injection. Administration of fr-HMGB1 prolonged the immobility duration in the tail suspension test (TST) and decreased sucrose preference. In addition to depressive behavior, the hippocampal TNF-α protein slightly increased. These depressive behaviors and upregulation of hippocampal TNF-α were alleviated or abrogated by pretreatment with the inhibitors AMD3100, FPS-ZM1, and TAK-242. Alternatively, nonoxid-HMGB1 failed to induce TNF-α protein or prolong the immobility duration. As expected, ds-HMGB1 administration substantially upregulated hippocampal TNF-α protein, increased the immobility time in the TST and decreased sucrose preference. Moreover, both glycyrrhizin and TAK-242 improved ds-HMGB1-induced depressive behavior. Furthermore, TAK-242 significantly blocked the upregulation of hippocampal TNF-α protein and protected hippocampal myelin basic protein from ds-HMGB1-induced reduction. These drugs had no effect on the total or central distance in the open field test. Collectively, this initial experiment demonstrates the role and receptor mechanisms of HMGB1 under different redox states on the induction of depressive-like behavior. Both ds-HMGB1 and fr-HMGB1 may induce depressive-like behavior in vivo mainly via neuroinflammatory response activation.

Outcomes of an extended Morrow procedure without a concomitant mitral valve procedure for hypertrophic obstructive cardiomyopathy.

The indications for a concomitant mitral valve (MV) procedure remain controversial for patients with hypertrophic obstructive cardiomyopathy (HOCM). According to previous studies, a concomitant MV surgery was required in 11-20% of inpatient operations. Thus, we aimed to study the outcomes of an extended Morrow procedure without a concomitant MV procedure for HOCM patients who had no intrinsic abnormalities of the MV apparatus. We retrospectively reviewed 232 consecutive HOCM patients who underwent extended Morrow procedures from January 2010 to October 2014. Only 10 (4.31%) patients with intrinsic MV diseases underwent concomitant MV procedures. Of the 232 patients, 230 had no to mild mitral regurgitation (MR) postoperatively. We separated the 232 patients into two groups according to preoperative MR degree. One group is mild MR, and the other is moderate or severe MR. The three-month, one-year, and three-year composite end-point event-free survival rates had no difference between two groups (p = 0.820). When we separated the patients to postoperative no or trace MR group and mild MR group, there was also no difference on survival rates (p = 0.830). In conclusion, concomitant mitral valve procedures are not necessary for HOCM patients with MR caused by systolic anterior motion, even moderate to severe extent.

Dexamethasone rapidly inhibits glucose uptake via non-genomic mechanisms in contracting myotubes.

Glucocorticoids (GCs) are a class of steroid hormones that regulate multiple aspects of glucose homeostasis. In skeletal muscle, it is well established that prolonged GC excess inhibits glucose uptake and utilization through glucocorticoid receptor (GR)-mediated transcriptional changes. However, it remains obscure that whether the rapid non-genomic effects of GC on glucose uptake are involved in acute exercise stress. Therefore, we used electric pulse stimulation (EPS)-evoked contracting myotubes to determine whether the non-genomic actions of GC were involved and its underlying mechanism(s). Pretreatment with dexamethasone (Dex, 10 µM) significantly prevented contraction-stimulated glucose uptake and glucose transporter 4 (Glut4) translocation within 20 min in C2C12 myotubes. Neither GC nuclear receptor antagonist (RU486) nor protein synthesis inhibitor (cycloheximide, Chx) affected the rapid inhibition effects of Dex. AMPK and CaMKII-dependent signaling pathways were associated with the non-genomic effects of Dex. These results provide evidence that GC rapidly suppresses glucose uptake in contracting myotubes via GR-independent non-genomic mechanisms. AMPK and CaMKII-mediated Glut4 translocation may play a critical role in GC-induced rapid inhibition of glucose uptake.

The expression and significance of five types of miRNAs in breast cancer.

BACKGROUND: This study aimed to investigate the expression and significance of 5 types of miRNAs in breast cancer to provide a theoretical and practical foundation for using these miRNAs in the diagnosis and treatment of breast cancer, thereby improving medical services. MATERIAL/METHODS: Stem-loop real-time RT-PCR was used to detect the expression levels of miR-145, miR-21, miR-10b, miR-125a, and miR-206 in 35 cases of breast cancer and adjacent normal breast tissues, and to analyze the relationship of miRNAs expression with clinicopathological features of breast cancer. The expression levels of estrogen receptor (ER) and progesterone receptor (PR) were examined by immunohistochemistry. Fluorescence in situ hybridization was used for the detection of HER-2 and TOP 2A. RESULTS: The expression levels of miR-145, miR-125a, and miR-206 in breast cancer were lower than those in adjacent normal tissues. MiR-145 was negatively correlated with tumor size, lymph node metastasis, ER, HER-2, and TOP 2A (P<0.05), regardless of age, menstruation, and PR. MiR-125a was correlated with negative node status, negative HER-2 status (P<0.05), whereas tumor size, age, menstruation, ER, and PR were independent factors. MiR-206 expression was correlated with negative ER status, negative PR status, and negative HER-2 status (P<0.05), regardless of age, menstruation, lymph node metastasis, and TOP 2A. MiR-21 and miR-10b expression in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.05). MiR-21 in post-menstrual patients with lymph node metastasis was highly expressed (P<0.05), and had no correlations with tumor size, ER, PR, and TOP 2A expression. MiR-10b expression was positively correlated with breast cancer tumor size, lymph node metastasis, and TOP 2A status (P<0.05), but had no correlations with age, menstruation, ER, PR, and HER-2. CONCLUSIONS: MiR-145, miR-21, miR-10b, miR-125a, and miR-206 may play important roles in breast cancer development and invasion.

A new and simple classification for the non-coronary sinus of Valsalva aneurysm.

OBJECTIVE: We introduce a simple classification of the non-coronary sinus of Valsalva aneurysm, and suggest a different approach for the corresponding type of non-coronary sinus of Valsalva aneurysm. METHODS: Between October 1996 and December 2009, 45 patients with non-coronary sinus of Valsalva aneurysm underwent surgical repair. Twenty-three were male and 22 female. The mean age was 32.80±11.77 years (range, 13-67 years). We divided them into two types, type I: rupture or protrusion into right atrium; and type II: rupture or protrusion into right atrium or right ventricle near or at the tricuspid annulus. For type I (n=32), the right atrium approach was chosen, using direct suture with patch repair. For type II (n=13), the transaortic approach with right atrium incision was chosen, with patch repair through an aortic incision and direct suture through a right atrium incision. Surgical results between types I and II were compared as regards cardiopulmonary bypass time, clamp aorta time, mechanical ventilation time, and intensive care unit time, and postoperative stay time. RESULTS: There was no early death after operation. There were no significant differences in cardiopulmonary bypass time, mechanical ventilation time, intensive care unit time, and postoperative stay time between two types (p>0.05). There was significant difference in clamp aorta time, with type II being longer than type I (p<0.05). Forty-three patients (93.33%) were followed up; one case of coronary artery disease using medication occurred, and there was no late death. CONCLUSIONS: Approach through the right atrium or right atrium with aortotomy showed the same early surgical results. Our classification of non-coronary SVA is simple and practical for clinical usage.

Is it possible to obtain "true endothelial progenitor cells" by in vitro culture of bone marrow mononuclear cells?

In vitro-cultured bone marrow cells have been shown to contain some low-density lipoprotein (LDL) uptake-positive cells. Although a small portion of LDL uptake-positive cells had expression for endothelial markers, all of them demonstrated a phagocytosis function similar to monocyte/macrophages and expression of the panleukocyte surface marker CD45 and monocyte marker CD14. These LDL uptake-positive cells did not show significant proliferative capacity and died out gradually in long-term culture. In contrast, the bone marrow-derived LDL uptake-negative cells showed strong proliferation and expression of typical mesenchymal surface markers CD29 and CD44. Although cultured under endothelial promoting conditions, these mesenchymal stem cells (MSCs) did not show any sign of differentiation toward endothelial cells. In conclusion, adult bone marrow-derived LDL uptake-positive cells that have been reported so far actually are monocytes/macrophages that can express some endothelial markers but are not "true endothelial progenitor cells" (EPCs). MSCs, which are the only cell type that shows strong proliferation during long-term adherent culture for bone marrow cells, do not differentiate toward the endothelial lineage when grown under endothelial promoting conditions.

Cartilage-derived stromal cells: is it a novel cell resource for cell therapy to regenerate infarcted myocardium?

Human cartilage is reported to contain multipotent stromal cells. We evaluated the effect of human cartilage-derived stromal cells (CDSCs) on heart function when transplanted into the infarcted myocardium of rats. CDSCs were isolated and cultured from human articular cartilage and subjected to fluorescence-activated cell sorting (FACS) analysis. The CDSCs were consistently negative for CD14, CD34, CD38, CD45, CD49f, CD104, CD105, CD106, CD117, HLA-DR, and ABCG-2, and positive for CD10, CD44, CD71, CD73, CD90, CD147, and HLA-A, -B, and -C by FACS analysis. Myocardial infarction (MI) was created in rats by ligation of the left anterior descending artery. Three weeks after MI, the CDSCs labeled with Hoechst stain were injected into the infarct and border zone. Echocardiography, histological examination, and reverse transcription-polymerase chain reaction (RT-PCR) were performed 4 weeks after cell transplantation. Echocardiography indicated that CDSC transplantation could improve heart function. The number of capillaries increased in the injection regions in the transplantation group. Histological examination showed that Hoechst-labeled CDSCs in islands within the infarcted region were stained positively for desmin and smooth muscle actin but negatively for alpha-sarcomeric actin and troponin-I. RT-PCR results indicated the expression level of collagen I, collagen III, tissue inhibitor of metalloproteinase-1, transforming growth factor-beta1, and vascular endothelia growth factor were much higher in the scar tissue in the transplantation group than in the medium and control groups. Our findings suggested that CDSCs might promote angiogenesis, prevent left ventricular remodeling, and improve the heart function when transplanted into injured heart in the rat model of myocardial infarction.