Successful management of camrelizumab-induced immune-checkpoint-inhibitors-related myocarditis.

INTRODUCTION: Immune checkpoint inhibitors can cause immune-related toxicity in various systems, with myocarditis being the most severe and life-threatening manifestation. This report presents a case in which myocarditis developed following administration of programmed cell death protein-1 (PD-1) inhibitors therapy. We describe the diagnosis and treatment of this patient in detail. CASE REPORT: We present the case of a 59-year-old female diagnosed with post-operative esophageal cancer and hepatic metastases. The patient underwent second-line treatment with domestically-made PD-1 inhibitor, camrelizumab, in combination with paclitaxel (albumin-bound) and carboplatin for two cycles. During the course of treatment, an electrocardiogram (ECG) revealed ST segment elevation in leads II, III, aVF, V2, V3, and V4, along with T wave changes in leads I and aVL. Laboratory examinations showed abnormal levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). Despite the absence of clinical symptoms, the patient was routinely hospitalized three weeks later. Based on the findings from the ECG, cardiac biomarkers, echocardiography, echocardiogram, cardiac magnetic resonance, and angiography, she was diagnosed with immune-checkpoint-inhibitors-related myocarditis. MANAGEMENT AND OUTCOME: The patient received immunoglobulin (0.5 g/kg/day) and was initially given methylprednisolone (1000 mg/day). Methylprednisolone was gradually reduced to 40 mg/day in 2 weeks. During this time, the levels of biomarkers indicative of myocardial injury also exhibited a simultaneous decline. DISCUSSION: This case highlights the importance of early detection and prompt intervention, including initiating appropriate steroid therapy and discontinuing of immune checkpoint inhibitors. Such measures can effectively prevent morbidity and mortality, ultimately leading to an improved prognosis.

Ablation of cardiomyocyte-derived BDNF during development causes myocardial degeneration and heart failure in the adult mouse heart.

Objective: Brain-derived neurotrophic factor (BDNF) and its receptor TrkB-T1 were recently found to be expressed in cardiomyocytes. However, the functional role of cardiomyocyte-derived BDNF in heart pathophysiology is not yet fully known. Recent studies revealed that BDNF-TrkB pathway plays a critical role to maintain integrity of cardiac structure and function, cardiac pathology and regeneration of myocardial infarction (MI). Therefore, the BDNF-TrkB pathway may be a novel target for myocardial pathophysiology in the adult heart. Approach and results: In the present study, we established a cardiomyocyte-derived BDNF conditional knockout mouse in which BDNF expression in developing cardiomyocytes is ablated under the control of the Myosin heavy chain 6 (MYH6) promoter. The results of the present study show that ablation of cardiomyocyte-derived BDNF during development does not impair survival, growth or reproduction; however, in the young adult heart, it causes cardiomyocyte death, degeneration of the myocardium, cardiomyocyte hypertrophy, left atrial appendage thrombosis, decreased cardiac function, increased cardiac inflammation and ROS activity, and metabolic disorders, leading to heart failure (HF) in the adult heart and eventually resulting in a decrease in the one-year survival rate. In addition, ablation of cardiomyocyte-derived BDNF during the developmental stage leads to exacerbation of cardiac dysfunction and poor regeneration after MI in adult hearts. Conclusion: Cardiomyocyte-derived BDNF is irreplaceable for maintaining the integrity of cardiac structure and function in the adult heart and regeneration after MI. Therefore, the BDNF-TrkB pathway will be a novel target for myocardial pathophysiology in the adult heart.

miR-486 improves fibrotic activity in myocardial infarction by targeting SRSF3/p21-Mediated cardiac myofibroblast senescence.

The regulation of fibrotic activities is key to improving pathological remodelling post-myocardial infarction (MI). Currently, in the clinic, safe and curative therapies for cardiac fibrosis and improvement of the pathological fibrotic environment, scar formation and pathological remodelling post-MI are lacking. Previous studies have shown that miR-486 is involved in the regulation of fibrosis. However, it is still unclear how miR-486 functions in post-MI regeneration. Here, we first demonstrated that miR-486 targeting SRSF3/p21 mediates the senescence of cardiac myofibroblasts to improve their fibrotic activity, which benefits the regeneration of MI by limiting scar size and post-MI remodelling. miR-486-targeted silencing has high potential as a novel target to improve fibrotic activity, cardiac fibrosis and pathological remodelling.

Temperature-Dependent Demography of Thrips hawaiiensis (Thysanoptera: Thripidae): Implications for Prevention and Control.

The Hawaiian flower thrips, Thrips hawaiiensis (Morgan), a common flower-inhabiting thrip, is now a potential pest globally. Effective control of T. hawaiiensis requires information about the effects of temperature on its ontogeny and population growth. In this study, the life history characteristics and demography of T. hawaiiensis were defined at eight temperatures (9-35°C). Additionally, the thermal constant and temperature threshold were estimated by regression analysis. The developmental duration and longevity of T. hawaiiensis decreased with an increase in temperature between 16°C and 32°C; females survived for longer than males at all temperatures. The lower temperature threshold and thermal constant of preadult T. hawaiiensis were 10.5°C and 132.5 degree-days, respectively. The oviposition days of the females gradually decreased from 16°C to 32°C, and net maternity was higher at 20°C than at 16°C, even though the same number of eggs were laid at both temperatures. The mean longevities of the populations were greatest at 20°C; the life expectancy and reproductive value decreased with temperature. The intrinsic rate of increase and finite rate of increase were significantly highest at 20°C, 25°C, and 30°C. Population growth was triggered at 12.3°C, and reached a peak at approximately 27°C when it proliferated to the largest population size. Therefore, the results suggest that although the population of T. hawaiiensis starts to grow at lower temperatures, it adapts to a wide range of temperatures, and these findings facilitate prediction of different stages of damage, population size, and seasonal occurrence of T. hawaiiensis.

Compatibility of six reduced-risk insecticides with Orius strigicollis (Heteroptera: Anthocoridae) predators for controlling Thrips hawaiiensis (Thysanoptera: Thripidae) pests.

Contact toxicity assessments of six reduced risk insecticides were carried out to compare their selectivity and sensitivity toward the minute pirate bug Orius strigicollis and its prey Thrips hawaiiensis. Additionally, and their potential exposure risk were evaluated for O. strigicollis. The LR50 value of acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb to T. hawaiiensis were 0.126, 2.093, 7.486, and 2.264 g a.i. ha-1, respectively, far less than the maximum field recommended rate (MFRR) for each. These four insecticides showed higher selectivity for predator and prey with selectivity ratio values of 37.3, 14.8, 22.1, and 119.3, respectively. However, the LR50 value of acetamiprid and emamectin benzoate were lower than MFRR, and unacceptable (approximately unacceptable for emamectin benzoate) risk to O. strigicollis in in-field, and the opposite results were shown in cyetpyrafen and indoxacarb. Although T. hawaiiensis was more sensitive to abamectin than O. strigicollis, the insecticide had poor selectivity for both test insects. The LR50 value of spirotetramat was more than 3 fold MFRR for T. hawaiiensis and O. strigicollis, showing extremely low contact toxicity and selectivity. In general, acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb showed high bioactivity against T. hawaiiensis, but only cyetpyrafen and indoxacarb could be well compatible with O. strigicollis, the combination of two insecticides with O. strigicollis indicated a potential strategy for the efficient and safe control of T. hawaiiensis.

Deciphering the in vivo Dynamic Proteomics of Mesenchymal Stem Cells in Critical Limb Ischemia.

OBJECTIVE: Regenerative therapy using mesenchymal stem cells (MSC) is a promising therapeutic method for critical limb ischemia (CLI). To understand how the cells are involved in the regenerative process of limb ischemia locally, we proposed a metabolic protein labeling method to label cell proteomes in situ and then decipher the proteome dynamics of MSCs in ischemic hind limb. METHODS AND RESULTS: In this study, we overexpressed mutant methionyl-tRNA synthetase (MetRS), which could utilize azidonorleucine (ANL) instead of methionine (Met) during protein synthesis in MSCs. Fluorescent non-canonical amino-acid tagging (FUNCAT) was performed to detect the utilization of ANL in mutant MSCs. Mice with hindlimb ischemia (HLI) or Sham surgery were treated with MetRSmut MSCs or PBS, followed by i.p. administration of ANL at days 0, 2 6, and 13 after surgery. FUNCAT was also performed in hindlimb tissue sections to demonstrate the incorporation of ANL in transplanted cells in situ. At days 1, 3, 7, and 14 after the surgery, laser doppler imaging were performed to detect the blood reperfusion of ischemic limbs. Ischemic tissues were also collected at these four time points for histological analysis including HE staining and vessel staining, and processed for click reaction based protein enrichment followed by mass spectrometry and bioinformatics analysis. The MetRSmut MSCs showed strong green signal in cell culture and in HLI muscles as well, indicating efficient incorporation of ANL in nascent protein synthesis. By 14 days post-treatment, MSCs significantly increased blood reperfusion and vessel density, while reducing inflammation in HLI model compared to PBS. Proteins enriched by click reaction were distinctive in the HLI group vs. the Sham group. 34, 31, 49, and 26 proteins were significantly up-regulated whereas 28, 32, 62, and 27 proteins were significantly down-regulated in HLI vs. Sham at days 1, 3, 7, and 14, respectively. The differentially expressed proteins were more pronounced in the pathways of apoptosis and energy metabolism. CONCLUSION: In conclusion, mutant MetRS allows efficient and specific identification of dynamic cell proteomics in situ, which reflect the functions and adaptive changes of MSCs that may be leveraged to understand and improve stem cell therapy in critical limb ischemia.

Comparative sensitivity of Neoseiulus cucumeris and its prey Tetranychus cinnabarinus, after exposed to nineteen pesticides.

The toxicity tests of nineteen commonly used pesticides were carried out to compare the sensitivity differences between predatory mite Neoseiulus cucumeris and its prey Tetranychus cinnabarinus by a "leaf spray method" in laboratory microcosms. For two avermectins, emamectin benzoate and abamectin, exhibited high bioactivity against T. cinnabarinusf with LR50 values of 0.04 and 0.05 g a.i./ha, respectively, but these two insecticides showed the opposite toxic effects to N. cucumeris. These two agents showed strong selectivity for the two test species with Selective Toxicity Rate (STR) values of 950 and 620, respectively. However, for five neonicotinoids, the LR50s of dinotefuran, thiamethoxam, imidacloprid, and acetamiprid were all greater than the recommended rates in the field except for clothianidin, and they showed no obvious toxicity difference to the two species with STR values ranging from 0.58 to 2.00. For two organophosphates, malathion is more toxic to N. cucumeris than T. cinnabarinus, however, dimethoate showed a higher toxic effect on T. cinnabarinus. In addition, the toxicity of four pyrethroids, bifenthrin, deltamethrin, cyhalothrin and gamma-cyhalothrin to N. cucumeris was higher than that of T. cinnabarinus, except for alpha-cypermethrin. For five acaricides, spirodiclofen, spirotetramat and pyridaben had no obvious selectivity to the two organisms, while diafenthiuron and chlorfenapyr were found to be highly toxic to T. cinnabarinus than N. cucumeris with STR values of 14.2 and 68.5, respectively. Thus, some pesticides above-mentioned like emamectin benzoate, abamectin, diafenthiuron and chlorfenapyr exhibited potential to be used in the management programs of T. cinnabarinus, especially in organically based production systems where there are fewer chemical control measures available, which need to combine with natural enemies to achieve the best control effect.

Prenatal and perinatal home environment and reported onset of wheeze, rhinitis and eczema symptoms in preschool children in Northern China.

Early life environment can affect asthma and allergies but few cohort studies on this issue are available from China. Our aim was to investigate reported onset of childhood wheeze, rhinitis and eczema symptoms in relation to prenatal, perinatal and postnatal home environment. Data on home environment and symptoms (ISAAC based questions) in first two years of life and in the past 12 months were reported by parents of the children (3-6 y) in a cross-sectional questionnaire survey in ten day care centers in Taiyuan, northern China (N = 3606). Changes of symptoms from the first 2 years of life to the past 12 months (recall period) were calculated retrospectively. Multilevel logistic regression analysis was applied. Reported onset of wheeze, rhinitis and eczema were 11.8%, 22.2% and 3.3%, respectively. Redecorating during pregnancy increased reported onset of rhinitis (OR = 2.29) and eczema (OR = 4.91). New furniture during pregnancy increased reported onset of rhinitis (OR = 1.47). Perinatal indoor mould increased reported onset of wheeze (OR = 1.51), rhinitis (OR = 1.65) and eczema (OR = 1.91). Perinatal mould odour increased reported onset of wheeze (OR = 1.85). Perinatal window pane condensation increased reported onset of wheeze (OR = 1.54) and rhinitis (OR = 1.24). Perinatal stuffy air and dry air in the home increased reported onset of all three symptoms (ORs 1.46-2.24). Dog keeping increased reported onset of wheeze (OR = 1.69) and eczema (OR = 2.13). Based on principal component analysis, four exposure scores were calculated (renovation, new furniture, mould and indoor air quality scores). Dose-response relationships were observed between these exposure scores and reported onset of symptoms. In conclusion, prenatal and postnatal exposure to emissions from renovation and new furniture can increase reported onset of childhood wheeze, rhinitis and eczema. Perinatal indoor mould, mould odour, condensation on window panes and impaired indoor air quality at home can be associated with reported development of wheeze, rhinitis and eczema in preschoolers in northern China.

Variation among 532 genomes unveils the origin and evolutionary history of a global insect herbivore.

The diamondback moth, Plutella xylostella is a cosmopolitan pest that has evolved resistance to all classes of insecticide, and costs the world economy an estimated US $4-5 billion annually. We analyse patterns of variation among 532 P. xylostella genomes, representing a worldwide sample of 114 populations. We find evidence that suggests South America is the geographical area of origin of this species, challenging earlier hypotheses of an Old-World origin. Our analysis indicates that Plutella xylostella has experienced three major expansions across the world, mainly facilitated by European colonization and global trade. We identify genomic signatures of selection in genes related to metabolic and signaling pathways that could be evidence of environmental adaptation. This evolutionary history of P. xylostella provides insights into transoceanic movements that have enabled it to become a worldwide pest.

Effects of spirodiclofen on life history traits and population growth of a spider mite predator Oligota flavicornis (Coleoptera: Staphyllinidae) based on the age-stage two-sex life table theory.

BACKGROUND: Knowledge of the compatibility between spirodiclofen and the predator Oligota flavicornis is an important aspect for the management of spider mites. RESULTS: We used the age-stage, two-sex life table to assess the effects of spirodiclofen on the life history traits and population growth of O. flavicornis. At the maximum recommended concentration (60 mg a.i. L-1 ) and also at twice the maximum recommended dosage (120 mg a.i. L-1 ), the preadult stages of O. flavicornis were significantly lengthened, while the adult longevity and fecundity decreased significantly. The finite rate (λ), intrinsic rate of increase (r), and net reproduction rate (R0 ) decreased, while the mean generation time (T) was longer after both the 60 and 120 mg a.i. L-1 treatments than it was in the control and 30 mg a.i. L-1 treatments. Life expectancy and reproductive value were higher in the control and 30 mg a.i. L-1 treatment than in the 60 and 120 mg a.i. L-1 treatments; the two higher concentrations were detrimental to the development of O. flavicornis. CONCLUSION: A proper combination of the O. flavicornis and spirodiclofen to control the spider mite, while avoiding the side effect of spirodiclofen, could be achieved based on the knowledge of life tables. © 2018 Society of Chemical Industry.

Effects of acetamiprid on life cycle development of predatory mite Amblyseius cucumeris (Acari: Phytoseiidae) after contact exposure.

Amblyseius cucumeris (Oudemans) is a beneficial non-target arthropod (NTA) and a key predator of pest mites in integrated pest management (IPM) programs across china. The toxic effects of insecticides have been extensively reported on predatory mites, but few studies devoted to the toxicity of compounds to A. cucumeris. In this study, the effects of a single application of acetamiprid against the A. cucumeris were investigated in a 48-h acute and a 30-d chronic test. In both tests the insecticide acetamiprid was applied once. In the acute test, the "open glass plate method" was used, with a 48-h LC50 value of 223.6 (149.8-336.9) mg a. i. L-1 for adult female. The LC50 was 1.49-fold the Maximum field recommended concentration. In the chronic test, exposure concentrations (1.12, 2.24, 4.47, 8.94, and 22.4 mg a. i. L-1) were designed based on a preliminary 48-h LC50 value for adult female. Above treatment levels of 2.24-4.47 mg a. i. L-1 reduce the total development time, survival rates and food consumption of A. cucumeris in different development stages. In addition, at acetamiprid concentrations higher than 2.24 mg a. i. L-1 serious effect on the capacity of oviposition of female adults were observed. However, even the highest treatment level of 22.4 mg a. i. L-1 did not affect egg hatching rates of exposed eggs. Acetamiprid had significant adverse effects on different development life stages of A. cucumeris. The results provide informative data for implementing biological and chemical control strategies in integrated pest management of spider mites.

Expanding the Scope of Polymerization-Induced Self-Assembly: Z-RAFT-Mediated Photoinitiated Dispersion Polymerization.

In this communication, we developed the first well-controlled Z-RAFT (RAFT = reversible addition-fragmentation chain transfer) mediated polymerization-induced self-assembly (PISA) formulation based on photoinitiated RAFT dispersion polymerization of tert-butyl acrylate (tBA) in ethanol/water (60/40, w/w) at room temperature using a Z-type macromolecular chain transfer agent (macro-CTA). Polymerizations proceeded rapidly via the exposure of visible-light irradiation (405 nm, 0.45 mW/cm2) with high monomer conversion (>95%) being achieved within 1 h. A variety of polymer nano-objects (spheres, worms, and vesicles) with narrow molar mass distributions were prepared by this Z-RAFT mediated PISA formulation. Silver nanoparticles were loaded with the vesicles via in situ reduction, which can be used as a catalyst for the reduction of methylene blue (MB) in the presence of NaBH4. Finally, gel permeation chromatography (GPC) analysis demonstrated that the corona block and the core-forming block could be cleaved by treating with excess initiator. This novel PISA formulation will greatly expand the scope of PISA and provide more mechanistic insights into the PISA research.

Temperature-Dependent Development of Oligota flavicornis (Coleoptera: Staphylinidae) Preying on Tetranychus cinnabarinus (Acarina: Tetranychidae).

The effect of nine constant temperatures on developmental time of Oligota flavicornis (Boisduval and Lacordaire) preying on Tetranychus cinnabarinus (Boisduval) (Acari: Tetranychidae) eggs was determined under laboratory conditions of 75 ± 5% RH and a 16:8 (L:D) h photoperiod. O. flavicornis survival rates were highest between 18 and 30°C, although O. flavicornis eggs developed successfully to adults at 12-32°C, and the developmental durations to adult at the seven temperatures (12, 15, 18, 20, 25, 30, and 32°C) were 114.41, 51.66, 33.45, 23.21, 13.43, 11.54, and 17.18 d, respectively. Two linear and seven nonlinear models (Logan-6 and Logan-10, Taylor, Lactin-1 and Lactin-2, and Brière-1 and Brière-2) were fit to the developmental rates of the immature predatory stages to estimate the thermal constant (K) and critical temperatures. The lower temperature threshold (T0) and K for the immature stages using the common linear model were 9.96°C and 225.73 degree-days and Ikemoto-Takai linear model were 11.01°C and 167.14 degree-days, respectively. The upper temperature threshold values estimated by the Logan-6 and Lactin-1 models were both 34.86°C. The T0 values estimated by the Brière-1 and Brière-2 models were 10.67 and 9.32°C for all immature stages, respectively, and the estimated optimal temperature according to the Brière-2 model was 29.59°C. Therefore, the two linear models and Brière-2 model estimates approximated the actual relationship between the temperature and developmental rate of immature O. flavicornis.

Adult Tea Green Leafhoppers, Empoasca onukii (Matsuda), Change Behaviors under Varying Light Conditions.

Insect behaviors are often influenced by light conditions including photoperiod, light intensity, and wavelength. Understanding pest insect responses to changing light conditions may help with developing alternative strategies for pest control. Little is known about the behavioral responses of leafhoppers (Hemiptera: Cicadellidae) to light conditions. The behavior of the tea green leafhopper, Empoasca onukii Matsuda, was examined when exposed to different light photoperiods or wavelengths. Observations included the frequency of locomotion and cleaning activities, and the duration of time spent searching. The results suggested that under normal photoperiod both female and male adults were generally more active in darkness (i.e., at night) than in light. In continuous darkness (DD), the locomotion and cleaning events in Period 1 (7:00-19:00) were significantly increased, when compared to the leafhoppers under normal photoperiod (LD). Leafhoppers, especially females, changed their behavioral patterns to a two day cycle under DD. Under continuous illumination (continuous quartz lamp light, yellow light at night, and green light at night), the activities of locomotion, cleaning, and searching were significantly suppressed during the night (19:00-7:00) and locomotion activities of both females and males were significantly increased during the day (7:00-19:00), suggesting a shift in circadian rhythm. Our work suggests that changes in light conditions, including photoperiod and wavelength, can influence behavioral activities of leafhoppers, potentially affecting other life history traits such as reproduction and development, and may serve as a method for leafhopper behavioral control.

Identification of Empoasca onukii (Hemiptera: Cicadellidae) and Monitoring of its Populations in the Tea Plantations of South China.

Tea green leafhoppers (Empoasca spp.) are considered one of the major pests in tea plantations in Asia. They are, however, difficult to monitor due to their size and flying and jumping abilities. In this study, we clarified the identification of the leafhopper species encountered in our study plantations and examined the impacts of sampling methods in estimating population abundance and sex ratio. The natural sex ratio of eggs, nymphs, and adults of tea green leafhopper and the differences between male and female were tested. Despite previous reports that Empoasca vitis (Goethe) was the major leafhopper present in our study area, our results showed that only Empoasca onukii Matsuda was found. Variation in population size over time and bias in sex ratio depending on the sampling methods were found in our monitoring experiments. In general, adult males were more attracted to yellow sticky cards than females. We believe that because female leafhoppers should be the target in pest control, yellow sticky cards may not be the most suitable monitoring or effective control of tea green leafhopper. We demonstrate the importance of understanding the implications of sampling techniques for population estimation and sex ratio bias as well as how temporal variation may affect monitoring results. Precise monitoring should take into consideration the different life histories of male and female.

All-cause mortality and cardiovascular events with nicorandil in patients with IHD: systematic review and meta-analysis of the literature.

BACKGROUND: Nicorandil is able to protect the cardiomyocytes from ischemic damage, but clear benefits of nicorandil in all-cause mortality and cardiovascular events were not consistently reported in patients with ischemic heart disease (IHD). MATERIALS AND RESULTS: Cochrane, PubMed, EMBASE, CBM, CNKI and Wangfang databases were searched for randomized controlled trials. Data on all-cause mortality and cardiovascular events were collected. Nicorandil groups were pooled to perform a comparison with control groups and to get the pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) for all-cause mortality, relative risks (RRs), and associated 95% CIs for cardiovascular events. STATA 11.0 software was used for all-cause mortality and cardiovascular events statistics. We retrieved 17 randomized controlled studies enrolling a total of 7305 patients. The addition of nicorandil treatment significantly reduced cardiovascular events (13.83% versus 18.01%; RR, 0.77; 95% CI, 0.69 to 0.86). No differences in all-cause mortality (3.83% versus 4.70%; OR, 0.81; 95% CI, 0.64 to 1.02), and repeat revascularization rate (13.06% versus 13.54%; RR, 0.95; 95% CI, 0.70 to 1.29) were observed. There was a weak linear association between cardiovascular events and nicorandil in IHD with diabetes (P=0.099). CONCLUSIONS: The results suggest that nicorandil as an adjunct therapy to IHD is associated with reduced cardiovascular events in patients with IHD.

Downregulation of HDAC1 is involved in the cardiomyocyte differentiation from mesenchymal stem cells in a myocardial microenvironment.

Under myocardial microenvironment, bone marrow-derived mesenchymal stem cells (MSCs) can transdifferentiate into cardiomyocytes (CMs). However, the role of histone deacetylase 1 (HDAC1) in this directed differentiation process remains unclear. The current study is to determine the acetylation regulatory mechanisms that may be involved in the directed CM differentiation from MSCs. MSCs isolated from male Sprague-Dawley (SD) rats were marked with Ad-EGFP and co-cultured with CMs. Flow cytometry was used to sort EGFP-positive (EGFP+) MSCs from the co-culture system. Then, the expression of cardiac troponin T (cTnT) in these MSCs was detected by immunofluorescence assay. In addition, HDAC1 levels at different co-culture times were measured by quantitative real-time polymerase chain reaction (QT-PCR) and Western blotting. At 4 days after co-culture with CMs, the MSCs began to expression detectable levels of cTnT. The expression of HDAC1 in CMs was much lower than that in MSCs. After co-culture with CMs, the expression of HDAC1 in MSCs was significantly decreased in a time dependent manner. In addition, our recent study has also identified that knockdown of the HDAC1 could promote the directed differentiation of MSCs into CMs. The results suggest that HDAC1 has a negative correlation with cardiac cell differentiation from MSCs under a myocardial microenvironment. HDAC1 might play an important role in the directed differentiation of MSCs into CMs in heart.

Knockdown of the HDAC1 promotes the directed differentiation of bone mesenchymal stem cells into cardiomyocytes.

Failure of the directed differentiation of the transplanted stem cells into cardiomyocytes is still a major challenge of cardiac regeneration therapy. Our recent study has demonstrated that the expression of histone deacetylase 1 (HDAC1) is decreased in bone mesenchymal stem cells (BMSCs) during their differentiation into cardiomyocytes. However, the potential roles of HDAC1 in cardiac cell differentiation of BMSCs, as well as the mechanisms involved are still unclear. In current study, the expression of HDAC1 in cultured rat BMSCs is knocked down by lentiviral vectors expressing HDAC1-RNAi. The directed differentiation of BMSCs into cardiomyocytes is evaluated by the expression levels of cardiomyocyte-related genes such as GATA-binding protein 4 (GATA-4), Nirenberg, Kim gene 2 homeobox 5 (Nkx2.5), cardiac troponin T (CTnT), myosin heavy chain (MHC), and connexin-43. Compared with that in control BMSCs, the expression of these cardiomyocyte-related genes is significantly increased in these HDAC1 deficient stem cells. The results suggest that HDAC1 is involved in the cardiomyocyte differentiation of BMSCs. Knockdown of the HDAC1 may promote the directed differentiation of BMSCs into cardiomyocytes.

The effects of simvastatin on left ventricular hypertrophy and left ventricular function in patients with essential hypertension.

This study is to evaluate the effects of Simvastatin on left ventricular hypertrophy and left ventricular function in patients with essential hypertension. Untreated or noncompliance with drug treatment patients with simple essential hypertension were treated with a therapy on the basis of using Telmisartan to decrease blood pressure (BP). There were 237 patients who had essential hypertension combined with left ventricular hypertrophy as diagnosed by echocardiography, taken after their BPs were decreased to meet the values of the standard normal. Among them, there were only 41 out of the original 237 patients, 17.3%, who had simple essential hypertension combined with left ventricular hypertrophy without any other co-existing disease. They were the patients selected for this study. All patients were randomly, indiscriminately divided into two groups: one was the control group (Group T), treated with the Telmisartan-based monotherapy; the other was the target group (Group TS), treated with the Telmisartan-based plus simvastatin therapy. The changes of left ventricular hypertrophy and left ventricular function were rediagnosed by echocardiography after 1 year. The results we obtained from this study were as follows: (i) The average BPs at the beginning of the study, of simple essential hypertension combined with left ventricular hypertrophy, were high levels (systolic blood pressure (SBP) 189.21 ± 19.91 mm Hg, diastolic blood pressure 101.40 ± 16.92 mm Hg). (ii) The Telmisartan-based plus simvastatin therapy was significantly effective in lowering the SBP (128.26 ± 9.33 mm Hg vs. 139.22 ± 16.34 mm Hg). (iii) After the 1-year treatment, the parameters of left ventricular hypertrophy in both groups were improved. Compared to group T, there were no differences in the characteristics of the subjects, including interventricular septum, left ventricular mass, left ventricular mass index, ejection fraction, left atrium inner diameter at baseline. The patients' interventricular septum (Group TS 10.30 ± 1.80 mm vs. Group T 10.99 ± 1.68 mm, P < .05), LVM (Group TS 177.43 ± 65.40 g vs. Group T 181.28 ± 65.09 g, P < .05), and LVMI (Group TS 100.97 ± 37.33 g/m(2) vs. Group T 106.54 ± 27.95 g/m(2), P < .05), all dropped more prominently (P < .05) in group TS; the ejection fraction rose more remarkably in group TS (Group TS: 57.50 ± 16.41% to 65.43 ± 11.60%, P < .01 while showing no change in Group T); the left ventricular hypertrophy reversed more significantly and the left ventricular systolic function improved more. (iv) The left atrium inner diameter of Group TS decreased (P < .01), the ratio of E/A, which indicates the left ventricular diastolic function, continued to drop further, showing no change to the trend of left ventricular diastolic function declination. Patients who have hypertension with left ventricular hypertrophy usually suffer other accompanying diseases at the same time. Telmisartan-based plus Simvastatin treatment can significantly reduce SBP, reverse left ventricular hypertrophy, improve the left ventricular systolic function, but it has no effect on reversing the left ventricular diastolic function. This experiment indicated that Simvastatin can reverse left ventricular hypertrophy and improve left systolic function.

Facile functionalization of polypeptides by thiol-yne photochemistry for biomimetic materials synthesis.

Rapid and highly efficient side-chain functionalization of polypeptides was achieved via combination of ring-opening polymerization of a new clickable monomer of γ-propargyl-L-glutamate N-carboxyanhydride (PLG-NCA) and thiol-yne photochemistry, which provides a convenient and universal route to prepare diverse polypeptide-based biomimetic hybrid materials.