Colistin, doxycycline and Labetalol-meropenem combination are the most active against XDR-Carbapenem-resistant Acinetobacter baumannii: Role of a novel transferrable plasmid conferring carbapenem resistance

Article

作者: Aboshanab, Khaled M ; Selim, Heba Mohammed Refat M. ; Elsayed, Khaled M ; Gomaa, Fatma Alzahraa M. ; Kamel, Noha A ; Kamel, Noha A. ; Aboshanab, Khaled M. ; Selim, Heba Mohammed Refat M ; Gomaa, Fatma Alzahraa M ; Elsayed, Khaled M. ; Alshahrani, Mohammad Y ; Alshahrani, Mohammad Y.

This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) A. baumannii clinical isolates. A total of 43 CR- A. baumannii were isolated of which 37 (86.6 %) and 28 (65 %) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1 % and 72.1 % of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4 % (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100 % and 91.4 % of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring aph-3', bla_oxa-58,bla_GIM3 and bla_CTX-M3 and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring bla_GIM3 gene in Egypt.

2024-10-01·Neurochemical Research

Neuroprotective Effects Exerted by a Combination of Selected Lactic Acid Bacteria in a Mouse Parkinsonism Model under Levodopa-Benserazide Treatment

Article

作者: de Moreno de LeBlanc, Alejandra ; Pérez Visñuk, Daiana ; LeBlanc, Jean Guy

Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies.

2024-09-01·Veterinary Microbiology

Host-derived lactic acid bacteria alleviate short beak and dwarf syndrome by preventing bone loss, intestinal barrier disruption, and inflammation

Article

作者: Sun, Maoyuan ; Xue, Yongzhi ; Xiang, Fengjun ; Zhang, Wuchao ; Lei, Baishi ; Zhao, Kuan ; Gao, Peipei ; Li, Limin ; Pan, Jialu ; Liu, Mandi ; Yuan, Wanzhe

Short-beak and dwarf syndrome (SBDS) is caused by novel goose parvovirus (NGPV) infection, which leads to farm economic losses. Our research aimed to investigate the potential of administering isolated lactic acid bacteria (LAB) in alleviating SBDS in ducks. Eight wild LAB strains were isolated from duck feces and their biosecurity was investigated in both duck embryo fibroblast (DEF) and live ducks. Moreover, the LAB strains exhibited no detrimental effects on bone metabolism levels and facilitated the tight junction proteins (TJPs) mRNA expression, and contributing to the mitigation of inflammation in healthy ducks. Subsequently, we conducted in vitrol and in vivo experiments to assess the impact of LAB on NGPV infection. The LAB strains significantly reduced the viral load of NGPV and downregulated the mRNA levels of pro-inflammatory factors in DEF. Additionally, LAB treatment alleviated SBDS in NGPV-infected ducks. Furthermore, LAB treatment alleviated intestinal damage, and reduced the inflammatory response, while also mitigating bone resorption in NGPV-infected ducks. In conclusion, the LAB strains isolated from duck feces have favorable biosecurity and alleviate SBDS in ducks, and the mechanism related to LAB improves intestinal barrier integrity, alleviates inflammation, and reduces bone resorption. Our study presents a novel concept for the prevention and treatment of NGPV, thereby establishing a theoretical foundation for the future development of probiotics in the prevention and treatment of NGPV.

项与 Sermorelin analogue(Akela Pharma, Inc.) 相关的新闻（医药）

2022-12-06

·生物制品圈

抗肿瘤疫苗跨越式进展！南京大学刘宝瑞教授团队开发出可促进全身抗肿瘤的原位疫苗

导读：原位接种是将免疫抑制性的肿瘤微环境转变为具有有限全身暴露和副作用的免疫刺激性微环境的一种很有前途的策略。然而，持续的临床效益需要长期和多层面的免疫激活，包括先天性免疫和适应性免疫。12月3日，南京大学医学院附属医院南京鼓楼医院刘宝瑞教授团队开发了一种表达fms样酪氨酸激酶3配体和共刺激物OX40配体融合蛋白的基于乳酸乳球菌的益生菌食品级原位接种(FOLactis)。研究论文“Engineered Lactococcus lactis secreting Flt3L and OX40 ligand for in situ vaccination-based cancer immunotherapy”发表在《Nature Communications》，结果证实，FOLactis 显示出增强的抗肿瘤免疫力，并成功地将“冷”肿瘤转化为“热”肿瘤。https://www.nature.com/articles/s41467-022-35130-7#Abs1研究背景 01 近年来，合成生物学的快速发展使设计用于治疗的智能微生物输送系统成为可能。更具体地说，细菌可以被改造成安全的、有针对性的、增强免疫力的药物携带者。其中，乳酸菌(LAB)等益生菌已在人体肠道中被发现，并对免疫治疗有积极影响。其具备的独特的特性使这些菌株吸引临床使用而不进一步衰减。目前为止，肿瘤内给药fms样酪氨酸激酶3配体(Flt3L)或OX40激动剂已应用于恶性血液病和一些实体瘤的临床试验，但收效甚微。快速降解限制了游离Flt3L或OX40激动剂的疗效，因此开发一种有效的载体，作为免疫佐剂，以最大限度地利用药物是至关重要的。与聚合物微球、微针贴片和可注射的水凝胶等其他生物材料相比，益生菌既能作为天然载体，同时又能激活先天和适应性免疫。研究进展 02 在这项工作中，研究人员设计了一个双功能工程乳酸乳球菌(FOLactis)，传递编码的Flt3L融合蛋白和共刺激物OX40配体(OX40L)。FOLactis的注射可通过直接细胞裂解杀死癌细胞，并诱导强烈的抗菌免疫反应，释放大量肿瘤特异性抗原。因此，这些抗原与细菌相关的危险信号结合，并促进TME和肿瘤引流淋巴结（TDLNs）中DC的抗原交叉呈递。表达Flt3L的FOLactis可直接扩大特异性交叉呈递DC亚群、常规1型树突状细胞（cDC1）特别是CD103+CD11c+和CD8α+CD11c+树突状细胞的局部增殖和分化，促进内源性抗肿瘤T细胞表位扩散并重新刺激肿瘤特异性CD8+T细胞。此外，TLRs激动剂已被证明与OX40信号传导同作用。研究人员假设乳酸乳球菌可以通过PAMPs26增加TME中CD4+ T细胞上OX40的表达，进一步最大化OX40L的作用，促进肿瘤浸润效应T细胞(Teff)的激活，抑制调节性T细胞(Treg)的功能。研究表明，双功能FOLactis主要通过增加TME中cDC1的数量和恢复细胞毒性T淋巴细胞反应，导致肿瘤明显消退。肿瘤内注射 FOLactis 以通过重新编程局部肿瘤和肿瘤引流淋巴结的免疫微环境来增强肿瘤免疫治疗的示意图最重要的是，这种ISV可以发挥一种异位效应，并与抗pd1抗体协同作用，将所谓的免疫沙漠或“冷”表型转化为“热”炎症肿瘤。总之，研究发现乳酸乳球菌有潜力成为传递免疫佐剂的平台，并提供对肿瘤再挑战的长期保护，对其他器官几乎没有伤害。研究意义 03 总之，研究人员描述了将 FOLactis 用作 ISV 的强大理由。研究结果证实，FOLactis 显示出增强的抗肿瘤免疫力，并成功地将“冷”肿瘤转化为“热”肿瘤。他们相信 FOLactis 代表了一个通用的疫苗平台，可以为广泛的实体瘤激发强大的先天性和肿瘤特异性适应性免疫反应。参考资料：https://www.nature.com/articles/s41467-022-35130-7#Abs1

免疫疗法疫苗临床研究

100 项与 Sermorelin analogue(Akela Pharma, Inc.) 相关的药物交易

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