Blapstin, a Diapause-Specific Peptide-Like Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera, Has Antifungal Function.

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera. It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 µM and 5.3 µM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs.

p38 MAPK is Crucial for Wnt1- and LiCl-Induced Epithelial Mesenchymal Transition.

Idiopathic pulmonary fibrosis (IPF) is characterized by myofibroblast foci in lung parenchyma. Myofibroblasts are thought to originate from epithelial-to-mesenchymal transition (EMT). Wnt1 and lithium chloride (LiCl) induce EMT in alveolar epithelial cells (AECs), but the mechanisms are unclear. AECs were treated with Wnt1 and LiCl, respectively; morphological change and molecular changes of EMT, including E-cadherin, fibronectin, and vimentin, were observed. SB203580 was administrated to test the role of p38 МАРК signaling in EMT. Then AECs were treated with siRNAs targeting p38 МАРК to further test the effects of p38 МАРК, and the role was further confirmed by re-expression of p38 МАРК. At last P-catenin siRNA was used to test the role of ß-catenin in the EMT process and relationship of ß-catenin and p38 МАРК was concluded. Exposure of AECs to Wnt1 and LiCl resulted in upregulation of vimentin and fibronectin with subsequent downregulation of E-cadherin. Wnt1 and LiCl stimulated the p38 МАРК signaling pathways. Perturbing the p38 МАРК pathway either by SB203580 or through p38 МАРК siRNA blocked EMT and inhibited fibronetin synthesis, which were reversed by transfection of p38 МАРК expression plasmid. ß-catenin siRNA attenuated the EMT process and decreased p38 МАРК phosphorylation, indicating that ß-catenin is involved in the EMTrelated changes through regulation of p38 МАРК phosphorylation. These findings suggest that p38 МАРК participates in the pathogenesis of EMT through Wnt pathway and that p38 МАРК may be a novel target for IPF therapy.

[Lemierre syndrome caused by Arcanobacterium haemolyticum: a case report and review of the literature].

OBJECTIVE: To emphasize the importance of the early diagnosis and treatment of Lemierre syndrome caused by Arcanobacterium haemolyticum. METHOD: A case of Lemierre syndrome caused by Arcanobacterium haemolyticum and three similar reported cases were reviewed. RESULTS: A man complained of fever with a sore throat, and examination found an enlarged left tonsil with prominent exudate, normal blood routine test and chest radiograph. Although the patient received the treatment of penicillin G and azithromycin, his condition worsened. Blood test showed white blood cell count 13.59×10(9)/L (neutrophils 0.933), platelet count 7.4×10(9)/L, TBil 54.3 mmol/L, DBil 28.3 mmol/L, AST 127 IU/L, ALT 82 IU/L, serum albumin 19.3 g/L with the development of the conditions. Blood cultures grew Arcanobacterium haemolyticum and the piperacillin-tazobactam was administered until fever was controlled. In addition, anticoagulation was administered when the thrombus was confirmed in the left internal jugular vein. Two follow-up clinic visits over the following 4 months were unremarkable. Besides three similar cases reported, four patients were male, and the ages ranged from 19 to 54 years. The chief complaints were sore throat and fever (4/4), with neck pain (4/4). Physical examinations found pharyngitis (2/4), exudate or abscess in the tonsillar crypt (2/4), maculopapular rashes (2/4). Laboratory results showed leukocytosis and thrombocytopaenia (4/4), acute cholestatic liver dysfunction (3/4), acute renal failure (2/4), acute respiratory failure (1/4). The first chest radiographs were normal at the onset, but chest radiography features included peripheral nodules and cavitation (3/4), focal or wedge-shaped lesions (1/4), pleural effusion (1/4) with the development of the conditions. Blood culture proved that there was only growth of Arcanobacterium haemolyticum (2/4), both Fusobacterium necrophorum and Arcanobacterium haemolyticum were found (2/4). Amoxicillin/clavulanic acid or piperacillin/tazobactam was administered (4/4). Neck CT proved internal jugular vein thrombosis (3/4) and anticoagulation was administered (3/4). All patients recovered and no one died. CONCLUSIONS: The characters of Lemierre syndrome include primary oropharynx infection, septicaemia, septic or embolic phlebitis of jugular vein, and metastatic abscess. Early recognition and aggressive intravenous broad-spectrum antibiotics are critical to reduce mortality.

[Treatment of polycystic ovarian syndrome with anovulatory infertility by ultrasound-guided immature follicle aspiration].

OBJECTIVE: To investigate the effect of ultrasound-guided immature follicle aspiration (IMFA) on polycystic ovarian syndrome (PCOS) in women with anovulatory infertility, such as the endocrinology of the patients and the basic follicles number in the ovaries, and to observe the ovarian response to human menopausal gonadotropin (hMG) stimulation and pregnancy after the therapy. METHODS: Seventy-one PCOS patients were involved in this trial, and divided into 2 groups. Thirty-seven patients of group I were primed with slight amount of hMG, the other 34 patients did not use hMG. Ultrasound-guided IMFA was performed 36 hour after human chorionic gonadotropin (hCG) administration. In the next cycle, the basal endocrinology and the basic number of follicles were checked, then IMFA were performed continuously until the basic number of follicles were under 10 per ovary. Afterwards, hMG were used to stimulate ovulation and the pregnant results were followed up. RESULTS: There were 37 cases (88 cycles) of PCOS patients in group I and 34 cases (87 cycles) in group II. After 2 to 3 treatment cycles, the testosterone level became normal in all of patients. The basic follicle number decreased to less than 10 per ovary in 33 cases (89%) in group I and 28 cases (82%) in group II. After hCG stimulation, all of them ovulated. Only 2 patients developed slight ovarian hyperstimulation syndrome (OHSS). Within 3 months after the procedure, 36 patients (51%) became pregnant by controlled ovarian hyperstimulation (COH) protocol after IMFA. CONCLUSIONS: Immature follicle aspiration treatment can improve the abnormal endocrinology, decrease the basic follicle number of the ovary, and achieve pregnancy in following COH cycles, meanwhile, avoid OHSS in PCOS patients.