Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans.

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 µM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.

Impact of Cr3+ pollution on microbial characteristics in purple paddy soil.

Impact of Cr(3+) pollution on soil microbial quantity, enzyme activity and biological activity in purple paddy soil were studied under incubation conditions. The results showed that amounts of all tested microbes and enzyme activities in soil were inhibited by low Cr(3+) concentration (200mg/kg). After 7-day incubation, sulfate-reducing activity, methanogen activity, denitrifying activity and anaerobic nitrogen-fixing activity in soil were reduced by 34%, 66%, 98% and 65% respectively. Amounts of soil microbes were remarkably inhibited with medium Cr(3+) concentration (400mg/kg), all with reduction of more than 50%; and all tested soil biological activity was almost recovered in the fourth week except soil denitrifying activity. Activities of urease, invertase, neutral phosphatase and catalase were decreased by 60%, 21%, 59% and 42%, respectively. With high Cr(3+) concentration (1600mg/kg), amounts and activities of tested microbes had only about 1% of that with control. As calculated from the regression equation, the ED50 (ecological dose) values of activities of soil urease, invertase and catalase were around 800mg/kg; the ED50 values of soil sulfate-reducing activity, methanogen activity and anaerobic nitrogen-fixing activity were also around 800mg/kg with an exception of soil denitrifying activity which ranged 35 to 39 mg/kg. According to the Standards of National Soil Environmental Quality in China and their sensitivities to 400mg/kg Cr(3+) concentration, quantity of denitrifying bacteria, urease activity and denitrifying activity could be selected as indicators of early warning for Cr(3+) pollution in purple paddy soil.

Microbial characteristics of purple paddy soil in response to Pb pollution.

The study focused on the change of microbial characteristics affected by Plumbum pollution with purple paddy soil in an incubation experiment. The results showed that low concentration of Plumbum had little effect on most of microbial amounts, biological activity and enzymatic activity. However, denitrifying activity was inhibited severely, and inhibition rate was up to 98%. Medium and high concentration of Plumbum significantly reduced the amounts and activity of all microorganisms and enzymatic activity, which increased with incubation time. Negative correlations were found between Plumbum concentrations and microbial amounts, biological activity and enzymatic activities except fungi and actinomyces. Thus they can be used to indicate the Plumbum pollution levels to some extent. LD(50) of denitrifying bacteria (DB) and ED50 of denitrifying activity were 852mg/kg and 33.5mg/kg. Across all test soil microbes, denitrifying bacteria was most sensitive to Plumbum pollution in purple paddy soil. Value of early warning showed that anaerobic cellulose-decomposing bacteria (ACDB) and actinomyces were also sensitive to Plumbum pollution. We concluded that denitrifying activity, actinomyces, ACDB or DB can be chosen as predictor of Plumbum contamination in purple paddy soil.

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.

Effect of MicroRNA145 on the multidrug resistance gene of ulcerative colitis in rats.

Multidrug resistance gene (MDR1a) and P-glycoprotein (P-gp) play an important role in the development of ulcerative colitis (UC) and influence the therapeutic effect of glucocorticoids, which may lead to drug resistance mechanically. UC may be related to miR-145 to some extent, and the relationship still needs further exploration. In this study we found that the expression of miR-145 was downregulated in the colonic tissues of rats with Dextran sodium sulfate (DSS)-induced UC. Also, the expression of MDR1a in colon tissues of each group negatively correlated with the expression of miR-145 in rats. The change in the plasma peak concentration (Cmax) in each group positively related to the miR-145 level. Mechanistically, miR-145 negatively regulated the expression and function of P-gp via acting directly on the 3'-UTR of MDR1 mRNA. Overall, these results indicated that miR-145 had a protective effect on the colorectal mucosa, and its downregulation may enhance the expression and function of MDR1a and P-gp, promoting the occurrence and development of UC. The downregulation of miR-145 reduced the drug sensitivity of 5-aminosalicylic acid (5-ASA) and glucocorticoids in treating UC, indicating that miR-145 might be a potential therapeutic target for UC.

Responses of annual herb plant community characteristics to increased precipitation and reduced wind velocity in semiarid sandy grassland.

Changes in precipitation regimes and wind velocity tend to alter structure and composition of the annual herb plant community, with consequent effects on ecological functioning and biodiversity maintenance. We examined the effects of increased precipitation and reduced wind velocity on annual herb plant community characteristics via a manipulative experiment from the middle of April to middle of August, 2016. There was significant increment in species richness with increased precipitation from June to August, and there were interactive effects between increased precipitation and reduced wind velocity especially in June and the end of July. From June to August, increased precipitation, reduced wind velocity as well as their interaction stimulated sandy plant community development. There was considerable elevation in plant coverage with increased precipitation, and also there was an interactive effect of increased precipitation with 20% reduced wind velocity. However, reduced wind velocity caused more significant stimulation (p < .01) in plant height. Moreover, dominant plants, Salsola collina, Bassia dasyphylla, and Setaria viridis, contributed equally to the elevated community coverage with increased precipitation, whereas S. collina occupied a much larger proportion on the augment of community height compared with the other two species under the increased precipitation and reduced wind velocity. Elevated Shannon-Wiener index was detected with increased precipitation in June and July. Furthermore, increased precipitation and reduced wind velocity enhanced aboveground and belowground biomass, respectively. These species traits-in structuring and composing plant community were suggested to be conducive to deep understanding the plant functioning and dynamics under global changing precipitation regimes and atmospheric wind velocity scenarios.

LncRNA SUMO1P3 drives colon cancer growth, metastasis and angiogenesis.

Long noncoding RNA (lncRNA) small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) acts a tumor promoter in several malignancies; however, its roles in colon cancer remain unclear. Herein, we demonstrated that SUMO1P3 expression was significantly higher in colon cancer tissues and cell lines than the corresponding non-tumor samples and normal colonic epithelial cells, respectively. The upregulation of SUMO1P3 was positively correlated with the advanced histological stages, metastases, angiogenesis and poor prognosis of colon cancer patients. SUMO1P3 knockdown repressed the proliferation, migration, invasion, and pro-angiogenesis of colon cancer cells in vitro. SUMO1P3 silencing reduced the growth, liver metastasis, and vascularization of colon cancer in vivo. Mechanistically, SUMO1P3 depletion decreased the levels of cyclin D1, Vimentin, and VEGFA while increased E-cadherin expression in xenograft tumor tissues. Overall, these results indicate that SUMO1P3 expedites the malignant behaviors of colon cancer and may be as a potential therapeutic target.

Comparative proteomic analysis of melanosis coli with colon cancer.

The present study aimed to investigate the proteomic difference between melanosis coli (MC) alone and melanosis coli with colon cancer (MCCC). Protein expression in patients with different diseases was analyzed using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/TOF-MS). A total of 14 protein differences with a confidence level of >95% were found. There were six differences between MC and normal tissues, in which two proteins exhibited upregulated expression levels and four proteins exhibited downregulated expression levels in MC. Furthermore, one protein was expressed only in MC (P<0.05). In addition, there were differences in the expression of eight proteins between MC and MCCC tissues, in which one protein had an upregulated expression in MC tissues and seven proteins had an upregulated expression in MCCC tissues. Furthermore, two proteins were only expressed in MCCC tissues (P<0.05). Eight proteins were identified using mass spectrometry and database search. In conclusion, comparative proteomics accurately displayed the expression differences in eight proteins between MC, MCCC and normal colon tissues.