Structure-activity relationships of a snake cathelicidin-related peptide, BF-15

Cathelicidin-BF15 (BF-15) is a 15-mer peptide derived from Cathelicidin-BF (BF-30), which is found in the venom of the snake Bungarus fasciatus and exhibits broad antimicrobial activity. Since BF-15 retains most part of the antimicrobial activity of BF-30 but has significantly reduced haemolytic activity and a much shorter sequence length (and less cost), it is a particularly attractive template around which to design novel antimicrobial peptides. However, the structure–activity relationship of it is still unknown. We designed and synthesized a series of C-terminal amidated analogs of BF-15 based on its amphipathic α-helix structure. And we characterized their antimicrobial potency and haemolytic activity. We identified the amidated BF-15 (analog B1) with potent antimicrobial activity against several antibiotic-resistant bacteria (MICs between 1 and 64 μg/mL, 2–16-folds higher than BF-30) and much lower haemolytic activity. The subsequent circular dichroism study results showed a typical α-helix pattern of analog B1 and the content of the α-helix structure of it increased significantly comparing with BF-30, which indicates the peptide sequence of BF-15 may provide a major contribution to the α-helix content of the whole BF-30 sequence. The peptide induced chaotic membrane morphology and cell debris as determined by electron microscopy. This suggests that the antimicrobial activity of B1 is based on cytoplasmic membrane permeability. Taken together, our results suggested that peptide B1 should be considered as an excellent candidate for developing therapeutic drugs.     

Scorpion Venom Heat-Resistant Peptide (SVHRP) Enhances Neurogenesis and Neurite Outgrowth of Immature Neurons in Adult Mice by Up-Regulating Brain-Derived Neurotrophic Factor (BDNF)

Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2’-dexoxyuridine (BrdU)-positive cells, BrdU- positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP.     

Acacetin antagonized lipotoxicity in pancreatic β-cells via ameliorating oxidative stress and endoplasmic reticulum stress

Molecular Biology Reports - During the pathogenesis and progression of diabetes, lipotoxicity is a major threat to the function and survival of pancreatic β-cells. To battle against the...     

GoNe encoding a class VIIIb AP2/ERF is required for both extrafloral and floral nectary development in Gossypium

The floral nectary, first recognized and described by Carl Linnaeus, is a remarkable organ that serves to provide carbohydrate-rich nectar to visiting pollinators in return for gamete transfer between flowers. Therefore, the nectary has indispensable biological significance in plant reproduction and even in evolution. Only two genes, CRC and STY, have been reported to regulate floral nectary development. However, it is still unknown what genes contribute to extrafloral nectary development. Here, we report that a nectary development gene in Gossypium (GoNe), annotated as an APETALA 2/ethylene-responsive factor (AP2/ERF), is responsible for the formation of both floral and extrafloral nectaries. GoNe plants that are silenced via virus-induced gene silencing technology and/or knocked out by Cas9 produce a nectariless phenotype. Point mutation and gene truncation simultaneously in duplicated genes Ne₁Ne₂ lead to impaired nectary development in tetraploid cotton. There is no difference in the expression of the CRC and STY genes between the nectary TM-1 and the nectariless MD90ne in cotton. Therefore, the GoNe gene responsible for the formation of floral and extrafloral nectaries may be independent of CRC and STY. A complex mechanism might exist that restricts the nectary to a specific position with different genetic factors. Characterization of these target genes regulating nectary production has provided insights into the development, evolution, and function of nectaries and insect-resistant breeding.     

Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway

Background: Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25–30% of which have dysregulation in the PI3K/AKT pathway. The present study investigated the anticancer effect of erianin on TNBC cell line and its underlying mechanism.Methods: After treatment with erianin, MTT assay was employed to determine the MDA-MB-231 and EFM-192A cell proliferation, the nucleus morphological changes were observed by DAPI staining. The cell cycle and apoptotic proportion were detected by flow cytometry. Western blot was performed to determine the cell cycle and apoptosis-related protein expression and PI3K pathways. Finally, the antiproliferative activity of erianin was further confirmed by adding or not adding PI3K agonists SC79.Results: Erianin inhibited the proliferation of MDA-MB-231 and EFM-192A cells in a dose-dependent manner, the IC₅₀ were 70.96 and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G₂/M phase, and the expressions of p21 and p27 were up-regulated, while the expressions of CDK1 and Cyclin B1 were down-regulated. Erianin also induced apoptosis via the mitochondrial pathway, with the up-regulation of the expression of Cyto C, PARP, Bax, active form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were down-regulated by erianin. After co-incubation with SC79, the cell inhibition rate of erianin was decreased, which further confirmed that the attenuated PI3K/Akt pathway was relevant to the pro-apoptotic effect of erianin.Conclusions: Erianin can inhibit the proliferation of TNBC cells and induce cell cycle arrest and apoptosis, which may ascribe to the abolish the activation of the PI3K/Akt pathway.     

Overexpression of ZEB2‐AS1 promotes epithelial‐to‐mesenchymal transition and metastasis by stabilizing ZEB2 mRNA in head neck squamous cell carcinoma

The long noncoding RNAs (lncRNAs) have been increasingly appreciated as key players underlying tumourigenesis and hold great potentials as prognostic biomarkers and therapeutic targets. However, their roles in head neck squamous cell carcinoma (HNSCC) have remained incompletely known. Here, we sought to reveal the oncogenic roles and clinical significance of a tumour‐associated lncRNA, zinc finger E‐box binding homeobox 2 antisense RNA 1 (ZEB2‐AS1), in HNSCC. ZEB2‐AS1 was aberrantly overexpressed in a fraction of HNSCC samples. Its overexpression significantly associated with large tumour size, cervical node metastasis and reduced overall and disease‐free survival. Antisense oligonucleotides (ASO)‐mediated ZEB2‐AS1 depletion markedly inhibited cell proliferation, migration and invasion while triggered apoptosis in HNSCC cells in part via modulating ZEB2 mRNA stability. Enforced overexpression of ZEB2 largely attenuated the phenotypic changes resulted from ZEB2‐AS1 inhibition except the impaired cell proliferation. In addition, ZEB2‐AS1 was required for TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) in vitro. Significantly reduced tumour growth and lung metastasis were observed in ZEB2‐AS1‐depleted cells in HNSCC xenograft animal models. Taken together, our findings reveal that overexpression of ZEB2‐AS1 associates with tumour aggressiveness and unfavourable prognosis by serving as a putative oncogenic lncRNA and a novel prognostic biomarker in HNSCC.     

3D–2D–0D Interface Profiling for Record Efficiency All‐Inorganic CsPbBrI2 Perovskite Solar Cells with Superior Stability

All‐inorganic CsPbBrI₂ perovskite has great advantages in terms of ambient phase stability and suitable band gap (1.91 eV) for photovoltaic applications. However, the typically used structure causes reduced device performance, primarily due to the large recombination at the interface between the perovskite, and the hole‐extraction layer (HEL). In this paper, an efficient CsPbBrI₂ perovskite solar cell (PSC) with a dimensionally graded heterojunction is reported, in which the CsPbBrI₂ material is distributed within bulk–nanosheet–quantum dots or 3D–2D–0D dimension‐profiled interface structure so that the energy alignment is optimized in between the valence and conduction bands of both CsPbBrI₂ and the HEL layers. Specifically, the valence‐/conduction‐band edge is leveraged to bend with synergistic advantages: the graded combination enhances the hole extraction and conduction efficiency with effectively decreased recombination loss during the hole‐transfer process, leading to an enhanced built‐in electric field, hence a high V_OC of as much as 1.19 V. The profiled structure induces continuously upshifted energy levels, resulting in a higher J_SC of as much as 12.93 mA cm^?2 and fill factor as high as 80.5%, and therefore record power conversion efficiency (PCE) of 12.39%. As far as it is known, this is the highest PCE for CsPbBrI₂ perovskite‐based PSC.     

Distribution of Illness and Medical Expenditure: A Survey in Two Villages in Rural Beijing

Background

The main goal of this study is to examine the distributions of illness conditions and resulting medical expenditures and their associated factors. To achieve this goal, an in-house survey was conducted in August of 2012 in rural Beijing, the capital city of China.

Results

The survey was conducted in Nanjianchang and Beijianchang, which are two villages 20 KM away from Miyun, a satellite city of Beijing. Data was collected on 346 households, which included 834 members. Variables measured included household characteristics, household head characteristics, illness conditions, and medical expenditures. Illness conditions and corresponding expenditure were measured for inpatient treatment, outpatient treatment, and self-treatment separately. Multivariate analysis suggested that the presence of inpatient treatment was associated with household head characteristics including age, gender, and education. The presence of a high level of outpatient treatment was associated with household head characteristics including gender and education. The presence of a high level of self-treatment was significantly associated with household size. In the analysis of overall out-of-pocket (OOP) medical expenditure, only age of household head was borderline significant. In the analysis of OOP inpatient expenditure, age and gender of household head were borderline significant. The OOP outpatient expenditure was associated with household size, presence of members older than 60, household head''s gender, marital status, and occupation. The OOP self-treatment expenditure was not associated with any household characteristic.

Conclusions

For the surveyed households, medical expenditure made up a considerable proportion of the total consumption. This study suggested that the presence of illness conditions and resulting OOP medical expenditure were associated with certain household and household head characteristics. Such results may help identify the subgroup that is the most affected by illness conditions. As this study collected recent data on inpatient, outpatient, and self-treatment separately, it may provide a useful complement to the existing studies.