Circulating exosomes repair endothelial cell damage by delivering miR-193a-5p

Circulating exosomes delivering microRNAs are involved in the occurrence and development of cardiovascular diseases. How are the circulating exosomes involved in the repair of endothelial injury in acute myocardial infarction (AMI) convalescence (3-7 days) was still not clear. In this study, circulating exosomes from AMI patients (AMI-Exo) and healthy controls (Normal-Exo) were extracted. In vitro and in vivo, our study showed that circulating exosomes protected endothelial cells (HUVECs) from oxidative stress damage; meanwhile, Normal-Exo showed better protective effects. Through the application of related inhibitors, we found that circulating exosomes shuttled between HUVECs via dynamin. Microarry analysis and qRT-PCR of circulating exosomes showed higher expression of miR-193a-5p in Normal-Exo. Our study showed that miR-193a-5p was the key factor on protecting endothelial cells in vitro and in vivo. Bioinformatics analyses found that activin A receptor type I (ACVR1) was the potential downstream target of miR-193a-5p, which was confirmed by ACVR1 expression and dual-luciferase report. Inhibitor of ACVR1 showed similar protective effects as miR-193a-5p. While overexpression of ACVR1 could attenuate protective effects of miR-193a-5p. To sum up, these findings suggest that circulating exosomes could shuttle between cells through dynamin and deliver miR-193a-5p to protect endothelial cells from oxidative stress damage via ACVR1.     

A review of the botany,traditional uses,phytochemistry and pharmacology of Nepeta tenuifolia Briq.

Phytochemistry Reviews - Nepeta tenuifolia (N. tenuifolia) is a common aromatic herb that is widespread in East Asia. The aerial parts and spikes can be used as the traditional phytomedicines for...     

Establishment of an efficient shoot regeneration system in vitro in Brassica rapa

In Vitro Cellular & Developmental Biology - Plant - To improve the genetic transformation system for Brassica rapa L., we established a high-efficiency shoot regeneration protocol. A double...     

Curcumin alleviates acute kidney injury in a dry‐heat environment by reducing oxidative stress and inflammation in a rat model

Curcumin exhibits anti‐inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry‐heat conditions. We divided Sprague‐Dawley rats into four groups: dry‐heat 0‐ (normal temperature control group), 50‐, 100‐, and 150‐minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high‐dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule‐1, and neutrophil gelatinase‐associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry‐heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150‐minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100‐ and 200‐mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX‐2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti‐inflammatory effects in a dry‐heat environment rat model.     

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma

Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 × 10⁶/kg. Grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.     

The pollination of Habenaria rhodocheila (Orchidaceae) in South China: When butterflies take sides

Habenaria is one of the largest terrestrial genera in the family Orchidaceae. Most field studies on Habenaria species with greenish–white and nocturnal scented flowers are pollinated by nocturnal hawkmoths and settling moths. However, H. rhodocheila presents reddish flowers lacking a detectable scent and fails to fit the moth pollination syndrome. We investigated the pollinators, breeding system, and functional traits of H. rhodocheila in South China and found that two diurnal swallowtail butterflies Papilio helenus and Papilio nephelus (Papilionidae) were the effective pollinators. When butterflies foraged for nectar in the spur, the pollinia became attached between the palpi. A triangular projected median rostellar lobe was found at the entrance (sinus) of the spur of H. rhodocheila. This lobe divided the spur opening into two entrances forcing butterflies to enter their proboscides through the left or right side. When the projection of median rostellar lobe was removed, the site of pollinium attachment changed to the eyes of the butterflies, leading to a higher rate of pollinium removal but lower rate of pollinium deposition. Our quartz glass cylinder choice experiment suggested that visual rather than olfactory cues provided the major stimuli for butterflies to locate these flowers. Hand pollination experiments suggested this species was self‐compatible but pollinator‐dependent. However, the proportion of seeds with large embryos produced in self‐pollinated fruits was significantly lower than in cross‐pollinated fruits, indicating a significant inbreeding depression. Unlike many other orchid species, fruit set was higher than rates of pollinium removal, indicating a high level of pollination efficiency in a species with friable pollinia. Shifts from moth to butterfly pollination in the genus Habenaria parallel other orchid lineages providing insights into the potential for pollinator‐mediated floral trait selection.     

Interacting effects of water temperature and dietary protein level on hematological parameters in Nile tilapia juveniles,Oreochromis niloticus (L.) and mortality under Streptococcus iniae infection

Based on central composite rotatable experimental design and response surface method, the interacting effects of temperature (20 °C–34 °C) and dietary protein level (25%–50%) on hematological parameters including red blood cell (RBC), white blood cell (WBC) and hemoglobin (Hb) of juvenile Oreochromis niloticus were studied under laboratory conditions. The experiment lasted for 7 weeks. After the feeding trial, fish were challenged with Streptococcus iniae and mortality was recorded for within 8 days. Results showed that the linear and quadratic effects of temperature on RBC, WBC and Hb were highly significant (P < 0.01). When the dietary protein level was 25%–50%, the RBC, WBC and Hb were increased firstly and then decreased, but the linear and quadratic effects of protein level were insignificant (P > 0.05). The interacting effects of temperature and protein level on RBC and Hb were significant (P < 0.05). The regression equations of RBC, WBC and Hb toward the two factors of interest were established, with the coefficients of determination being 0.870, 0.836 and 0.881, respectively (P < 0.01). These equations could be used for prediction in practice. After the challenge, the mortalities for the combinations of 22.1 °C/28.7% and 20.0 °C/37.5% were significantly higher than 27.0 °C/37.5% (P < 0.05). The optimal temperature/dietary protein level combination was obtained at 27.9 °C/38.1% at which the lowest mortality (13.76%) was attained. This value was close to the optimal temperature/dietary protein level combination (29.4 °C/41.9%) for the greatest levels of RBC (2.560 × 10⁶ μL^?1), WBC (270.648 × 10³ μL^?1) and Hb (92.851 g L^?1). The results of this study indicated that preferred temperature/dietary protein level combination might strengthen the non-specific immunity and reduce susceptibility to S. iniae.     

Heterogeneous interactome between Litopenaeus vannamei plasma proteins and Vibrio parahaemolyticus outer membrane proteins

A great loss has been suffered by microbial infectious diseases under intensive shrimp farming in recent years. In this background, the understanding of shrimp innate immunity becomes an importantly scientific issue, but little is known about the heterogeneous protein–protein interaction between pathogenic cells and hosts, which is a key step for the invading microbes to infect internet organs through bloodstream. In the present study, bacterial outer membrane (OM) protein array and pull-down approaches are used to isolate both Vibrio parahaemolyticus OM proteins that bind to shrimp serum proteins and the shrimp serum proteins that interact with bacterial cells, respectively. Three interacting shrimp serum proteins, hemocyanin, β-1,3-glucan binding protein and LV_HP_RA36F08r and thirty interacting OM proteins were determined. They form 63 heterogeneous protein–protein interactions. Nine out of the 30 OM proteins were randomly demonstrated to be up-regulated or down-regulated when bacterial cells were cultured with shrimp sera, indicating the biological significance of the network. The interesting findings uncover the complexity of struggle between host immunity and bacterial infection. Compared with our previous report on heterogeneous interactome between fish grill and bacterial OM proteins, the present study further extends the investigation from lower vertebrates to invertebrates and develops a bacterial OM protein array to identify the OM proteins bound with shrimp serum proteins, which elevates the frequencies of the bound OM proteins. Our results highlight the way to determine and understand the heterogeneous interaction between hosts and microbes.     

遗传性肾炎的遗传学研究进展

遗传性肾炎(hereditary nephritis,HN)是一组与遗传有关,主要累及肾小球的肾脏疾病,常伴有其它器官的损伤.HN呈家族聚集性,可表现为常染色体显性遗传、常染色体隐性遗传和X连锁遗传,有些家系还表现为非孟德尔遗传和线粒体遗传.对HN主要疾病的临床表型、遗传学和动物模型的总结和对HN疾病的深入研究有可能找到疾病的致病突变,以及更好地了解疾病的分子机制.