Morphological characteristics and phylogenetic analyses revealed four new wood inhabiting fungi (Agaricomycetes, Basidiomycota) in Xizang Autonomous Region, China.

Four new fungi from Xizang in southwest China, Caloceraramaria, Ceraceomycesrhizomorphus, Leptosporomyceslinzhiensis, and Ramariaxizangensis are described and illustrated based on the morphological and molecular evidence. Caloceraramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomycesrhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyceslinzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramariaxizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4-5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

Simvastatin ameliorates synaptic plasticity impairment in chronic mild stress-induced depressed mice by modulating hippocampal NMDA receptor.

BACKGROUND: In our previous study, we showed simvastatin exerts an antidepressant effect and inhibits neuroinflammation. Given the role of synaptic impairment in depression development, we investigate the effect of simvastatin on synaptic plasticity in depression and the related mechanisms. METHODS: Electrophysiological analysis, Golgi staining, and transmission electron microscope were performed to analyze the effect of simvastatin on synaptic impairment in depression. In addition, the localization and reactivity of N-methyl-D-aspartate receptor (NMDAR) subunits and the downstream signaling were investigated to explore the mechanism of simvastatin's effect on synaptic plasticity. RESULTS: Simvastatin ameliorated the reduction of the magnitude of long-term potentiation (LTP) in Schaffer collateral-CA1, restored hippocampal dendritic spine density loss, improved the number of spine synapses, reversed the reduction in BrdU-positive cells in chronic mild stress (CMS)-induced depressed mice, and ameliorated NMDA-induced neurotoxicity in hippocampal neurons. Dysfunction of NMDAR activity in the hippocampus is associated with depression. Simvastatin treatment reversed the surface expression and phosphorylation changes of NMDAR subunits in NMDA-treated hippocampal neurons and depressed mice. In addition, simvastatin further increased the levels of mature BDNF, activating TrkB-Akt-mTOR signaling, which is critical for synaptic plasticity. CONCLUSIONS: These findings suggest that simvastatin can improve the dysfunction of NMDAR and ameliorate hippocampal synaptic plasticity impairment in depressed mice.

Enlargement of the knowledge of Cortinarius section Anomali (Agaricales, Basidiomycota): introducing three new species from China.

Cortinarius is a globally distributed agaricoid genus that has been well studied in Europe and America with over 1,000 described species. However, as part of an ongoing effort to investigate the diversity of Cortinarius section Anomali in China, the resource investigation and classification research are still limited, and the species diversity has not been clarified by far. During the re-examination of the Chinese Cortinarius specimens, C. cinnamomeolilacinus, C. subclackamasensis, and C. tropicus, belonging to the sect. Anomali, were described in China as new to science based on morphological examination and phylogenetic analysis. The three new species are described and illustrated in detail according to the Chinese materials. The phylogenetic analysis based on internal transcribed spacer sequences confirmed the placement of the three species in the Cortinarius sect. Anomali clade. Phylogenetically related and morphologically similar species to these three new species are discussed.

Taxonomy and phylogeny of Sidera (Hymenochaetales, Rickenella clade) from China and North America revealing two new species.

Sidera, belonging to the Rickenella clade of Hymenochaetales, is a worldwide genus with mostly poroid hymenophore of wood-inhabiting fungi. Two new species in the genus, Sideraamericana and S.borealis, are described and illustrated from China and North America based on morphological and molecular evidence. They were mainly found growing on rotten wood of Abies, Picea and Pinus. S.americana is characterized by annual, resupinate basidiomata with silk sheen when dry, round pores (9-11 per mm), a dimitic hyphal system, and allantoid basidiospores measuring 3.5-4.2 × 1 µm. S.borealis is characterized by annual, resupinate basidiomata with cream to pinkish buff dry pore surface, angular pores (6-7 per mm), a dimitic hyphal system, and allantoid basidiospores measuring 3.9-4.1 × 1-1.1 µm. Phylogenetic analysis based on a combined 2-locus dataset [ITS1-5.8S-ITS2 (ITS) + nuclear large subunit RNA (nLSU)] shows that the two species are members of Sidera, and they are compared with morphologically similar and phylogenetically related species, respectively. An identification key to 18 accepted species of Sidera in worldwide is provided.

Two new species of Antrodia (Polyporales, Basidiomycota) in western China.

Two new species of Antrodia, A. aridula and A. variispora, are described from western China. Phylogeny based on a six-gene dataset (ITS + nLSU + nSSU + mtSSU + TEF1 + RPB2) demonstrates that samples of the two species form two independent lineages within the clade of Antrodia s.s. and are different in morphology from the existing species of Antrodia. Antrodia aridula is characterized by its annual and resupinate basidiocarps with angular to irregular pores of 2-3 mm each and oblong ellipsoid to cylindrical basidiospores measuring 9-12 × 4.2-5.3 µm, growing on gymnosperm wood in a dry environment. Antrodia variispora is characterized by its annual and resupinate basidiocarps with sinuous or dentate pores with a size of 1-1.5 mm each and oblong ellipsoid, fusiform, pyriform, or cylindrical basidiospores measuring 11.5-16 × 4.5-5.5 µm, growing on the wood of Picea. The differences between the new species and morphologically similar species are discussed in this article.

Morphological and phylogenetic evidence reveal three new Pseudohydnum (Auriculariales, Basidiomycota) species from North China.

Pseudohydnum is characterized by gelatinous basidiomata with hydnoid hymenophores and longitudinally septate basidia. In this study, samples of the genus from North China were examined morphologically and phylogenetically using a dataset of the internal transcribed spacer of the ribosomal RNA gene and the nuclear large subunit rDNA. This study describes three new species, namely Pseudohydnum abietinum, Pseudohydnum candidissimum, and Pseudohydnum sinobisporum. Pseudohydnum abietinum is characterized by pileate and pale clay pink basidiomata when fresh, with a rudimentary stipe base, four-celled basidia, and broadly ellipsoid to ovoid or subglobose basidiospores (6-7.5 × 5-6.3 µm). P. candidissimum is characterized by very white basidiomata when fresh, frequently four-celled basidia, and broadly ellipsoid to subglobose basidiospores (7.2-8.5 × 6-7 µm). P. sinobisporum is characterized by ivory basidiomata when fresh, two-celled basidia, ovoid to broadly ellipsoid, or subglobose basidiospores (7.5-9.5 × 5.8-7.2 µm). The main characteristics, type localities, and hosts of Pseudohydnum species are listed.

Inhibition of hexokinase 2 with 3-BrPA promotes MDSCs differentiation and immunosuppressive function.

The adoptive transfer of ex vivo generated myeloid-derived suppressor cells (MDSCs) may be a promising therapeutic strategy for preventing allograft rejection after solid organ transplantation. Currently, the precise role of immune-metabolic pathways in the differentiation and function of MDSCs is not fully understood. Hexokinase 2 (HK2) is an isoform of hexokinase and is a key enzyme involved in the increased aerobic glycolysis of different immune cells during their activation and function. Here, we demonstrate that the addition of HK2 inhibitor 3-Bromopyruvic acid (3-BrPA) into traditional MDSCs induction system in vitro significantly promoted MDSCs production and enhanced their immunosuppressive function. Treatment with 3-BrPA increased the expression of MDSC-related immunosuppressive molecules, such as iNOS, Arg1, and CXCR2. Moreover, the adoptive transfer of 3-BrPA-treated MDSCs significantly prolonged the survival time of mouse heart allografts. This study provides a novel strategy to solve the problems of harvesting enough autologous cells for MDSC production from sick patients, and producing functionally enhanced MDSCs for preventing graft rejection and inducing tolerance.

[Cross-Sectional Study of Nutritional Status and Dietary Nutrient Intake in Children with Duchenne Muscular Dystrophy (DMD) in China].

Objective: To investigate the dietary nutrient intake and the nutritional status of children with Duchenne muscular dystrophy (DMD), and to explore the correlation between them, so as to provide theoretical basis for the formulation of proper nutritional treatment for children with DMD. Methods: A total of 223 children aged 2 to 14 years who came to West China Second University Hospital, Sichuan University from July 2017 to April 2021, and who were diagnosed with DMD by genetic testing were enrolled as the subjects of the study. Dietary assessment was conducted with a 3-day 24-hour dietary recall, and serum vitamin D level was measured by chemiluminescence method. Results: Only 33.2% of the children with DMD were found to be of normal nutritional status. The incidences of stunted growth, underweight, overweight and obesity were 13.5%, 14.4%, 14.3% and 8.1%, respectively. Among the children with DMD, those with serum vitamin D deficiency and insufficiency accounted for 9.0% and 89.7%, respectively. According to the dietary recall of the children with MDM, the daily energy ratio of carbohydrate, protein and fat were (47.40±6.64)%, (14.46±2.22)%, and (38.17±5.30)%, respectively. The daily intake of dietary calcium and vitamin D were (433.32±164.39) mg per day and (155.73±89.30) IU per day, respectively. The ratio of daily protein intake to the estimated average requirement for protein ( P=0.003) and ratio of daily energy intake to the estimated energy requirement ( P=0.007) were lower in children with stunted growth than those of DMD children of normal nutritional status. Conclusion: The dietary structure of children with DMD is obviously not suited to their condition and nutritional deficiency coexists with overnutrition among them. Further research needs to be done for developing appropriate nutritional guidance programs and standardized nutritional management measures for children with DMD.

Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy.

Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28-6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1-1.5 million IU/day, given in 2-3 doses, could attain PTA > 90% for MICs ≤ 0.5 µg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 µg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 µg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 µg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended.

Phylogeny and Diversity of the Genus Pseudohydnum (Auriculariales, Basidiomycota).

The toothed jelly fungus Pseudohydnum gelatinosum was originally described from Europe. The name has a broad sense and the species has been widely reported almost all over the world. We have studied samples of so-called P. gelatinosum from Asia and Oceania. Based on morphology, hosts, geography, and phylogenetic analysis using the internal transcribed spacer regions (ITSs) and the large subunit of nuclear ribosomal RNA gene (nLSU), four new species, P. himalayanum, P. orbiculare, P. sinogelatinosum, and P. tasmanicum, from China, New Zealand, and Australia are described and illustrated, and a new combination, Pseudohydnum totarae, is proposed. The five new taxa can be differentiated by the shape of their basidiomata, pileal surface color when fresh, spine size, basidiospore dimensions, shape of hyphidia, hosts, and biogeography. Phylogenetically, most of these taxa are distantly related, and different base pairs among these taxa mostly account for >2% nucleotides in the ITS regions.

Two new species of Boletopsis (Bankeraceae, Thelephorales) from Southwest China.

Two new species of Boletopsis, B.macrocarpa and B.tibetana, are described and illustrated from Southwest (SW) China based on morphology, ecology and phylogenetic analyses by the internal transcribed spacer regions (ITS) and the large subunit of nuclear ribosomal RNA gene (nLSU). Boletopsismacrocarpa is characterized by big basidiocarps (up to 18 cm in diam), guttulate basidiospores, and the presence of gloeoplerous hyphae in context and growing in pure forest of Pinusyunnanensis. Boletopsistibetana is characterized by smaller pores (3-4 per mm), the presence of gloeoplerous hyphae in pileipellis, and the growth in forests of Picea. Phylogenetically, the two new species are grouped in two independent lineages nested in Boletopsis. In addition, one sample from Northeast China is temporarily treated as Boletopsis sp. 1 because of the single sample; another Chinese sample from SW China is sister to B.grisea in phylogeny, and it is treated as B.cf.grisea because the morphological difference between B.cf.grisea and B.grisea is indistinct. Furthermore, the main characteristics of Boletopsis species are listed, and a key to accepted species of Boletopsis is provided.

[Clinical application of the modified pediatric nutritional risk screening tool].

OBJECTIVE: To study the clinical application of the modified nutritional risk screening tool and nutrition assessment in pediatric patients in China, and to provide a theoretical basis for establishing a standardized nutritional management process for pediatric patients. METHODS: A retrospective analysis was performed for the nutritional risk screening and nutrition assessment data of 16 249 hospitalized children. According to the degree of nutritional risk, the children were divided into a high nutritional risk group with 588 children, a moderate nutritional risk group with 4 330 children, and a non-nutritional risk group with 11 331 children. Nutrition assessment results were compared between groups. The composition of nutritional risk screening scores and the impact of nutritional risk screening on the rate of nutrition support therapy were analyzed. RESULTS: The incidence rate of nutritional risk was 30.27% (4 918/16 249), and the incidence rates of malnutrition and overnutrition were 27.37% (4 448/16 249) and 11.29% (1 834/16 249), respectively. Nutrition assessment results were significantly correlated with nutritional risk (≥ 5 years old:rs=0.313, P < 0.05; < 5 years old:rs=-0.304, P < 0.05). There was a significant difference in the composition of scoring items between the groups with different nutritional risks (P < 0.05). With the implementation of nutritional risk screening, there was a gradual increase in the rate of nutrition support therapy year by year (P < 0.05). CONCLUSIONS: There is a high incidence rate of nutritional risk in hospitalized children. The use of the modified pediatric nutritional risk screening tool can promote the implementation of standardized nutritional management.

Diagnostic and prognostic roles of soluble CD22 in patients with Gram-negative bacterial sepsis.

BACKGROUND: Soluble CD22 (sCD22) is a fragment of CD22, a B cell-specific membrane protein that negatively regulates B-cell receptor signaling. To date, sCD22 has only been regarded as a tumor marker of B-cell malignancies. Its expression in infectious diseases has not yet been assessed. METHODS: Serum concentrations of sCD22, procalcitonin (PCT) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays in patients with intra-abdominal Gram-negative bacterial infection. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers in this type of infection. The correlations between biomarkers and the Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. RESULTS: Concentrations of sCD22 were significantly elevated in patients with sepsis and the elevation is correlated with the severity of sepsis. sCD22 was also slightly elevated in patients with non-infected systemic inflammatory response syndrome or local infection. The diagnostic accuracy of sCD22 for sepsis was equivalent to that of PCT or IL-6. In addition, the correlation of sCD22 with APACHE II scores was stronger than that of PCT or IL-6. CONCLUSIONS: Serum sCD22 is a novel inflammatory mediator released during infection. This soluble biomarker plays a potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic accuracy as efficient as that of PCT or IL-6. Furthermore, sCD22 is more valuable to predict the outcomes in patients with sepsis than PCT or IL-6. The present study suggested that sCD22 might be potentially useful in supplementing current criteria for sepsis.

Analysis on safety and value of CT-guided percutaneous chemical ablation in treatment of pelvic hypovascular metastasis.

OBJECTIVE: To investigate the clinical efficacy of CT-guided percutaneous chemical ablation in treatment of pelvic hypovascular metastasis. METHODS: Based on a retrospective analysis of the clinical data of 78 patients with pelvic hypovascular metastasis, CT-guided percutaneous chemical ablation was used to directly puncture lesions. The emulsion consisting of ultra-liquid iodized oil, anhydrous ethanol and oxaliplatin in the proportion of 1:2:2 was slowly injected to the lesions, which should be filled to the greatest extent. The postoperative follow-up lasted for 2~51 months. RESULTS: After surgery, 23 of these 78 cases were reported with merely residual fibrous cords or calcified shadow or complete recovery, and the lesion volume was reduced by ≥ 50% in 55 cases compared to that before surgery, indicating a total effective rate of 100% (78/78). The tumor size after treatment was significantly reduced compared to that before treatment [(4.5 ± 1.9) cm(2) vs (20.6 ± 10.1) cm(2)], and the difference was statistically significant (P = 0.018). Of 34 patients suffering from pain in perineum, buttocks and/or legs and limited mobility of the lower extremities, eliminated pain were reported in 13 cases and relieved symptoms in 21 cases. No intraoperative and postoperative complications were observed. CONCLUSION: In treatment of pelvic hypovascular metastasis, CT-guided percutaneous chemical ablation proves to be minimally invasive, effective and worthy of clinical promotion.

Synergisms of cardiovascular effects between iptakalim and amlodipine, hydrochlorothiazide or propranolol in anesthetized rats.

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and ß receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.

Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy.

Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K(ATP)) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel K(ATP) channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A(2). Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy.

[Telemetry EEG of parietal association cortex in heroin-induced CPP rats].

OBJECTIVE: To determine the relationship between EEG changes of parietal association cortex (PtA) and drug-seeking behaviors of heroin-induced conditioned place preference (CPP) rats. METHODS: Stereotaxic electrode was buried in the PtA of rats, which were then divided randomly into heroin-induced CPP group and operation-only control group. A CPP video system in combination with EEG wireless telemetry was used for recording PtA EEG and the behaviors of the rats-staying in black or white chamber of the video box; shuttling between black-white chambers or between white-black chambers. RESULTS: No significant difference in percentage of the telemetry EEG waves was found between the two groups of rats when they stayed in the black or white chambers. The heroin-induced CPP rats had increased percentage of delta waves (P < 0.05) on the right PtA and decreased percentage of beta and beta2 waves on both right and left PtA (P < 0.05) when they shuttled between two chambers. Compared with the operation-only controls, significant decrease in the percentage of delta waves on both left and right PtA and increase in theta, alpha and alpha1 waves were evident (P < 0.05) only when the heroin-induced CPP rats shuttled between white-black chambers. CONCLUSION: EEG changes on PtA of heroin-induced CPP rats differ between staying and shuttling states. Such changes may not be associated with drug-seeking behaviors.

Role of Wnt/ß-catenin signaling pathway in the mechanism of calcification of aortic valve.

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/ß-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells (VICs) were isolated, cultured and stimulated with oxidized low density lipoprotein (ox-LDL) for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/ß-catenin signaling pathway, such as glycogen synthase kinase 3ß (GSK-3ß) and ß-catenin, were detected by using Western blotting and real-time polymerase chain reaction (PCR). The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3ß and ß-catenin were increased significantly in VICs after stimulation for 48 h (P<0.05). It is suggested that Wnt/ß-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.

[Effects of ATP-sensitive potassium channel opener iptakalim against ventricular remodeling and its mechanisms of endothelial protection].

OBJECTIVE: To study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats. METHODS: ISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2). RESULTS: Six weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks). CONCLUSION: Ipt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

Activation of aryl hydrocarbon receptor prolongs survival of fully mismatched cardiac allografts.

Recent data suggest that activation of aryl hydrocarbon receptor (AhR) by its high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in expansion of regulatory T (Treg) cells and suppresses the development of autoimmune and allergic diseases in several models. Treg cells have been increasingly documented to suppress allograft rejection and even to establish stable long-term graft acceptance. However, the involvement of TCDD in the regulation of solid organ transplantation rejection is largely unknown. Here, we examined whether activation of AhR with TCDD altered cardiac allograft rejection in an allogeneic heart transplant model. Recipient C57BL/6 (H-2b) mice were administrated with a single intraperitoneal injection of TCDD, and the murine cardiac transplant models from BALB/c (H-2d) to C57BL/6 (H-2b) were built 24 h later. The complete cessation of cardiac contractility was defined as the observation endpoint. The effect of TCDD on T-cell proliferation was assessed by mixed lymphocyte reaction (MLR). Histological and immunohistochemical analyses were performed to estimate the severity of rejection. The phenotype and cytokine profile of lymphocytes were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Activation of AhR remarkably prolonged the survival of cardiac allografts to more than 20 days. In vitro, TCDD ugregulated the frequency of CD4+CD25+Foxp3+ Treg cells and suppressed the proliferation of T lymphocytes. In vivo, the prolonged survival time was associated with increased number of Treg cells in allografts and spleens. Furthermore, the secretion of interferon-γ (IFN-γ) and interleukin-17 (IL-17) was reduced to less than 50% of that of the PBS treatment control group by TCDD treatment, whereas IL-10 was elevated to 10-fold of that of the PBS treatment control group. Collectively, our data indicate that activation of AhR with a single dose of TCDD significantly prolonged the survival of fully allogeneic cardiac grafts, and the mechanism underlying this effect might be involved in the induction of Treg cells.