乳酸菌作为药物分子粘膜投递载体的研究进展

乳酸菌是被公认为安全的食品级微生物,广泛地应用于食品生产、保存以及作为益生菌促进人类健康。鉴于发展有效的投递药物分子策略的需要,乳酸菌成为了极有吸引力的用于口服、鼻饲及阴道进行粘膜投递药物分子的活载体。用乳酸菌作为药物分子的投递载体,安全性好,且可直接合成并投递目标蛋白,显著降低药物生产成本。到目前为止,乳酸菌作为粘膜投递载体,已成功地向粘膜组织投递了一系列功能蛋白用以治疗多种疾病。文中综述了近20年的数据,重点聚焦乳酸菌作为药物分子投递载体的发展和应用,为今后乳酸菌作为活载体的临床研究提供一定参考。     

猪肌肉的转录组学研究进展

猪在中国的畜牧业及人类疾病的研究中有着不可或缺的作用,一方面猪提供了人类日常所需的肉类食物,另一方面在人类的器官移植方面的研究甚为广泛.因此,对于猪的各方面的研究都较为广泛,但在肌肉mRNA转录组方面涉及不深.转录组包括编码RNA和非编码RNA,根据测序结果,通过对不同品种的同位基因进行比较,用来分析相互之间的差异,进而分析不同的生物现象以及发病机制.利用这一特性,将国内外猪种的肌肉在生长过程中的编码RNA和非编码RNA进行研究,其潜在的意义是降低中国地方猪的脂肪含量.本综述旨在对转录组学、测序技术和转录组学研究以及猪基因的研究进行归纳,为进一步提高中国本土猪的瘦肉率提供了参考.     

菜籽饼肥对香蕉枯萎病的防效及其对土壤细菌的影响

研究菜籽饼肥对香蕉枯萎病的防治效果,探究菜籽饼肥施用后对土壤细菌群落的影响.设置2组实验,CN组为菜籽饼肥处理组,YN组为对照实验组.种植120d后,统计各组的发病率;利用qPCR技术检测2组中的FOC4孢子数量;采集2组土壤,利用Illumina Miseq高通量测序平台对CN处理组与YN对照组的土壤细菌群落结构和差异进行分析对比.实验研究发现:(1)施菜籽饼肥的CN处理组枯萎病发病率比YN对照组低63.33％;施用菜籽饼肥的处理土壤中FOC4的数量由2.94×104个/克土下降为1.96×103个/克土,YN对照组土壤中FOC4孢子的数量由2.94×104个/克土上升为4.55×105个/克土,CN处理组较YN对照组枯萎病菌数量下降了 2个数量级;(2)土壤细菌宏基因组微生物分类测序结果显示,CN处理组的Alpha多样性指数均优于YN对照组,这表明施用菜籽饼肥后增加了土壤细菌群落的丰度及多样性;(3)在门水平上,菜籽饼肥处理增加了变形菌门(Proteobacteria)和拟杆菌门(Bacteroidetes)的相对丰度,同时也降低了酸杆菌门(Acidobact-eria)、厚壁菌门(Firmicutes)和Patescibacteria等菌门的相对丰度;在属水平,CN处理组中的不动杆菌属(Aci-netobacter)、水杆菌属(Aquabacterium)、热单胞菌属(Thermomonas)、产黄杆菌属(Rhodanobacter)、假单胞菌属(Pseudomonas)和奥托氏菌属(Ottowia)等菌属的相对丰度较YN对照组有明显提高,而酸热菌属(Acidother-mus)、Bryobacter菌属以及Acidipila等菌属相对丰度较YN对照组有所减少.施用菜籽饼肥可以改变土壤中细菌的群落结构,显著降低土壤中FOC4孢子数量,从而降低香蕉枯萎病的发病率.本研究结果为菜籽饼肥用于香蕉枯萎病综合防控提供了理论依据.     

The ScCas9++ variant expands the CRISPR toolbox for genome editing in plants

The development of clustered regularly interspaced palindromic repeats (CRISPR)-associated protein (Cas) variants with a broader recognition scope is critical for further improvement of CRISPR/Cas systems. The original Cas9 protein from Streptococcus canis (ScCas9) can recognize simple NNG-protospacer adjacent motif (PAM) targets, and therefore possesses a broader range relative to current CRISPR/Cas systems, but its editing efficiency is low in plants. Evolved ScCas9⁺ and ScCas9⁺⁺ variants have been shown to possess higher editing efficiencies in human cells, but their activities in plants are currently unknown. Here, we utilized codon-optimized ScCas9, ScCas9⁺ and ScCas9⁺⁺ and a nickase variant ScCas9n⁺⁺ to systematically investigate genome cleavage activity and cytidine base editing efficiency in rice (Oryza sativa L.). This analysis revealed that ScCas9⁺⁺ has higher editing efficiency than ScCas9 and ScCas9⁺ in rice. Furthermore, we fused the evolved cytidine deaminase PmCDA1 with ScCas9n⁺⁺ to generate a new evoBE4max-type cytidine base editor, termed PevoCDA1-ScCas9n⁺⁺. This base editor achieved stable and efficient multiplex-site base editing at NNG-PAM sites with wider editing windows (C₋₁–C₁₇) and without target sequence context preference. Multiplex-site base editing of the rice genes OsWx (three targets) and OsEui1 (two targets) achieved simultaneous editing and produced new rice germplasm. Taken together, these results demonstrate that ScCas9⁺⁺ represents a crucial new tool for improving plant editing.     

Viral RNA-binding ability conferred by SUMOylation at PB1 K612 of influenza A virus is essential for viral pathogenesis and transmission

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.     

Protective Effects of Pidotimod Against Salmonella Infections

International Journal of Peptide Research and Therapeutics - Pidotimod has been shown to exhibit immunomodulatory activities and exert protective effects against bacterial infections. This study...     

Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus

Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.     

Atrial Natriuretic Peptide (ANP) Regulates the Biological Activity of EGF/EGFR System in Adult Retinal Pigment Epithelial Cell

International Journal of Peptide Research and Therapeutics - Atrial natriuretic peptide (ANP) is a type of peptide hormone secreted by atrial cells, which has many important biological functions...     

PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells

Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers.