Mechanism of action of chounghwamycin A

The mechanism of action of chounghwamycin A to tumor cells resembles that of actinomycin D, preferentially inhibiting the synthesis of RNA. The interaction of chounghwamycin A with DNA was studied, and the results indicated that chounghwamycin A could not cause any scission in tested DNA. However, an induced mobility shift of the DNA in agarose gel electrophoresis was observed. When the concentration of chounghwamycin A gradually increased, the migration rate of closed circular form DNA is gradually slowed. At a critical concentration of chounghwamycin A, 15.6 micrograms/ml, the migration rate of closed circular form DNA reaches its minimum value. As more choungwamycin A is added, the mobility of the closed circular DNA increases gradually again, suggesting that the intercalation of chounghwamycin A in DNA is the primary mechanism of its action against tumor cells.     

Over-expression of CXCR4 on mesenchymal stem cells protect against experimental colitis via immunomodulatory functions in impaired tissue

Bone marrow-derived mesenchymal stem cells (BMSCs) are attractive candidates for tissue regeneration and immunoregulation in inflammatory bowel disease. However, their in vivo reparative capability is limited owing to barren efficiency of BMSCs to injury region. Stromal cell-derived factor (SDF-1) plays an important role in chemotaxis and stem cell homing through interaction with its specific receptor CXC chemokine receptor 4 (CXCR4). The present study was designed to investigate the role of SDF-1α/CXCR4 axis in the therapeutic effects of lentivirus-preconditioned BMSCs for 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis rats. BMSCs were isolated from female Sprague–Dawley rats and identified by flow cytometry. Lentiviral transduction was applied to over-express CXCR4/GFP (Ad-CXCR4-BMSCs) or null/GFP (Ad-GFP-BMSCs). Efficacy of engraftment was determined by the presence of enhanced green fluorescent protein (GFP) positive cells. One week after intravenous administration, Ad-GFP-BMSCs failed to colonize in the inflamed colon and had no beneficial effect in TNBS-induced colitis. Instead, Ad-CXCR4-BMSCs signally ameliorated both clinical and microanatomical severity of colitis. Immunofluorescence and western blotting showed that Ad-CXCR4-BMSCs migrated toward inflamed colon was more efficient than Ad-GFP-BMSCs. The therapeutic effect of Ad-CXCR4-BMSCs was mediated by the suppression of pro-inflammatory cytokines and STAT3 phosphorylation in injured colon. Collectively, our data indicated that over-expression CXCR4 led to enhance in vivo mobilization and engraftment of BMSCs into inflamed colon where these cells can function as an anti-inflammatory and immunomodulatory component of the immune system in TNBS-induced colitis.     

Diethylstilbestrol regulates mouse gubernaculum testis cell proliferation via PLC‐Ca2+‐CREB pathway

Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system, but the mechanism remains unclear. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernaculum testis cells, but the underlying mechanism is unclear. In this study, mouse gubernaculum testis cells were pretreated with phospholipase C (PLC) inhibitor U‐73122 and then treated with DES. The results demonstrated that U‐73122 impaired DES‐evoked intracellular Ca2+ mobilization in gubernaculum testis cells and inhibited DES‐induced proliferation of gubernaculum testis cells. Mechanistically, we found that U‐73122 inhibited DES‐induced activation of cAMP‐response element binding protein (CREB) in gubernaculum testis cells. In conclusion, these data suggest that the effects of DES on mouse gubernaculum testis cells are mediated by PLC‐Ca²⁺‐CREB pathway.

Significance of the study

Environmental estrogens remain a serious threat to male reproductive health, and it is important to understand the mechanism by which EEs affect the male productive system. Here we explore potential mechanisms how the proliferation and contractility of gubernaculum testis cells are regulated by diethylstilbestrol. Our findings provide the first evidence that PLC‐Ca²⁺‐CREB signalling pathway mediates the nongenomic effects of diethylstilbestrol on gubernaculum testis cells. These findings provide new insight into the role of diethylstilbestrol in the aetiology of male reproductive dysfunction and will help develop better approaches for the prevention and therapy of male reproductive malformation.     

Optimized blood cell profiling method for genomic biomarker discovery using high-density microarray

High-quality biomarkers for disease progression, drug efficacy and toxicity liability are essential for improving the efficiency of drug discovery and development. The identification of drug-activity biomarkers is often limited by access to and the quantity of target tissue. Peripheral blood has increasingly become an attractive alternative to tissue samples from organs as source for biomarker discovery, especially during early clinical studies. However, given the heterogeneous blood cell population, possible artifacts from ex vivo activations, and technical difficulties associated with overall performance of the assay, it is challenging to profile peripheral blood cells directly for biomarker discovery. In the present study, Applied BioSystems' blood collection system was evaluated for its ability to isolate RNA suitable for use on the Affymetrix microarray platform. Blood was collected in a TEMPUS tube and RNA extracted using an ABI-6100 semi-automated workstation. Using human and rat whole blood samples, it was demonstrated that the RNA isolated using this approach was stable, of high quality and was suitable for Affymetrix microarray applications. The microarray data were statistically analysed and compared with other blood protocols. Minimal haemoglobin interference with RNA labelling efficiency and chip hybridization was found using the TEMPUS tube and extraction method. The RNA quality, stability and ease of handling requirement make the TEMPUS tube protocol an attractive approach for expression profiling of whole blood to support target and biomarker discovery.     

Species delimitation in the Chinese bamboo partridge Bambusicola thoracica (Phasianidae; Aves)

Although tropical and subtropical Asia harbour a high level of species diversity, their species richness can be underestimated because species which are in fact distinct have not been separately identified. In this study, we delimit Bambusicola thoracica into two full species, the Chinese bamboo partridge (B. thoracica) in continental Asia and the Taiwanese bamboo partridge (B. sonorivox) on the island of Taiwan, using coalescent‐based multilocus division and diagnosable vocalization patterns. Isolation‐with‐migration analysis indicated that the two bamboo partridges diverged approximately 1.8 million years ago, with gene flow present most probably during the early stages of their divergence. This conclusion supports the hypothesis that diverging lowland lineages spread across the Asian mainland, and continental islands have more opportunities for secondary contact than highland ones when the sea level was low. Our results imply that conservation of biodiversity in tropical and subtropical Asia could be hindered by overlooking numerous ‘hidden’ species and highlight the importance of re‐examining the taxonomic statuses of species in this region traditionally defined as polytypic.     

中国沟胫天牛亚科一新属及一新种（鞘翅目：天牛科）

本文记述天牛科沟胫天牛亚科１新属，球胸天牛属Ｇｉｂｂｏｈａｍｍｕｓｇｅｎ．ｎｏｖ．和１新种：缩颈球胸天牛Ｇｉｂｂｏｈａｍｍｕｓｓｔｒｉｃｔｉｃｏｌｌｉｓｓｐ．ｎｏｖ。     

Pathogens and drug-resistance of hospital-acquired pneumonia in an EICU in Tianjin,China

Objective: Observing the pathogens and drug-resistance within hospital-acquired pneumonia (HAP) in an emergency intensive care unit (EICU) to provide a reference for clinically reasonable use of antibiotics. Methods: Sixty-two patients with HAP in Tianjin Medical University General Hospital from January 2017 to May 2019 were analyzed retrospectively. Bacterial identification and susceptibility were reviewed. Results: One hundred and thirty-seven strains of pathogenic bacteria were isolated from 62 patients, with 97.1% Gram-negative and only 2.9% Gram-positive. There were also six fungal isolates. The most common pathogens were Acinetobacter baumannii, accounting for 30.8% of all isolates, followed by Klebisella spp, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Escherichia coli. Acinetobacter baumannii was poorly susceptible to piperacillin-tazobactam, cefepime, Amoxicillin+clavulonic acid, ciprofloxacin. However, the isolates were sensitive to Tigecycline, so as the isolates of Klebisella spp. Pseudomonas aeruginosa was mostly sensitive to Amikacin, followed by Tobramycin. All of the isolates of Staphylococcus aureus were susceptible to Linezolid, Tigecycline and Vancomycin. Conclusions: Gram-negative bacteria especially Acinetobacter baumannii, are the main pathogens for HAP in the observed EICU. The variety of pathogens should be monitored at regular intervals to improve resistance issues and therapeutic effect.