The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and a murine peritoneum model

The global spread of antimicrobial resistance and the increasing number of immune‐compromised patients are major challenges in modern medicine. Targeting bacterial virulence or the human host immune system to increase host defence are important strategies in the search for novel antimicrobial drugs. We investigated the inflammatory response of the synthetic short antimicrobial peptide LTX21 in two model systems: a human whole blood ex vivo model and a murine in vivo peritoneum model – both reflecting early innate immune response. In the whole blood model, LTX21 increased the secretion of a range of different cytokines, decreased the level of tumour necrosis factor (TNF) and activated the complement system. In a haemolysis assay, we found 2.5% haemolysis at a LTX21 concentration of 500 mg/L. In the murine model, increased influx of white blood cells (WBCs) and polymorphonuclear neutrophils (PMNs) in the murine peritoneal cavity was observed after treatment with LTX21. In addition, LTX21 increased monocyte chemoattractant protein‐1 (MCP‐1). In conclusion, LTX21 affected the inflammatory response; the increase in cytokine secretion, complement activation and WBC influx indicates an activated inflammatory response. The present results indicate the impact of LTX21 on the host–pathogen interplay. Whether this will also affect the course of infection has to be investigated.     

The extracellular matrix enriched with membrane metalloendopeptidase and insulin‐degrading enzyme suppresses the deposition of amyloid‐beta peptide in Alzheimer's disease cell models

Amyloid plaque is a typical feature of Alzheimer's disease (AD) and is one of the targets for AD therapy. Membrane metalloendopeptidase (MME) and insulin‐degrading enzyme (IDE) are two types of proteases that could cleave beta‐amyloid (Aβ) peptides generated by neuron cells of AD patients. Extracellular matrix (ECM) plays a crucial role in regulating tissue‐specific functions and is an ideal biomaterial for tissue repair. In this study, we extracted the liquid ECM enriched with collagen‐binding‐domain‐fused IDE or MME from human foreskin fibroblast cells. We found that these ECM biomaterials reduced the aggregation of Aβ peptides, prevented the formation of amyloid plaques, and also suppressed phosphorylation of Tau protein in AD cell models. Overall, our research provides a novel ECM biomaterial that can be potentially used for AD therapy.     

An update on polymer-lipid hybrid systems for improving oral drug delivery

Introduction: A promising approach that has recently emerged to overcome the complex biobarriers and interrelated challenges associated with oral drug absorption is to combine the benefits of polymeric and lipid-based nanocarriers within one hybrid system. This multifaceted formulation strategy has given rise to a plethora of polymer-lipid hybrid (PLH) systems with varying nanostructures and biological activities, all of which have demonstrated the ability to improve the biopharmaceutical performance of a wide range of challenging therapeutics.

Areas covered: The multitude of polymers that can be combined with lipids to exert a synergistic effect for oral drug delivery have been identified, reviewed and critically evaluated. Specific focus is attributed to preclinical studies performed within the past 5 years that have elucidated the role and mechanism of the polymer phase in altering the oral absorption of encapsulated therapeutics.

Expert opinion: The potential of PLH systems has been clearly identified; however, improved understanding of the structure–activity relationship between PLH systems and oral absorption is fundamental for translating this promising delivery approach into a clinically relevant formulation. Advancing research within this field to identify optimal polymer, lipid combinations and engineering conditions for specific therapeutics are therefore encouraged.     

Collagen extraction and recent biological activities of collagen peptides derived from sea-food waste: A review

Mostly, collagen is obtained from mammalian sources, but its use is limited because of high cost and various allergic reactions. In this review, different alternative sources of collagen were explored and methods for isolation and peptide generations are summarized. Bioactive peptides are short sequences of 2–20 amino acid residues with positive effect on human health. This review summarizes various biological activities of sea food derived peptides/hydrolysates includes antioxidant, inflammatory, antifreeze, angiotension-I converting enzyme (ACE-I) inhibition, antimicrobial, antiaging, wound healing and anticoagulant activities. Moreover, this review also highlights the therapeutic potential and importance of sea-food derived peptides in various pharmaceutical, biomedical, food and cosmetic industries. This review also proposes biological solution for utilization of seafood derived waste in the development of collagen-based food ingredients that is otherwise cause environmental pollution.     

Identification and Characterization of Edible Cricket Peptides on Hypertensive and Glycemic In Vitro Inhibition and Their Anti-Inflammatory Activity on RAW 264.7 Macrophage Cells

Recent studies continue to demonstrate the potential of edible insects as a protein base to obtain bioactive peptides applicable for functional food development. This study aimed at identifying antihypertensive, anti-glycemic, and anti-inflammatory peptides derived from the in vitro gastrointestinal digests of cricket protein hydrolysates. After sequential fractionation, the protein digest subfraction containing the lowest molecular weight (<0.5 kDa), hydrophobic (C18) and cationic peptides (IEX) was found responsible for the most bioactivity. The cationic peptide fraction significantly reduced (p < 0.05) α-amylase, α-glucosidase, and angiotensin converting enzyme (ACE) activity in vitro, and also inhibited the expression of NF-κB in RAW 264.7 macrophage cells. A total of 28 peptides were identified with mass spectrometry (LC–MS/MS) and de novo sequencing from the potent fraction. Three novel peptides YKPRP, PHGAP, and VGPPQ were chosen for the molecular docking studies. PHGAP and VGPPQ exhibited a higher degree of non-covalent interactions with the enzyme active site residues and binding energies comparable to captopril. Results from this study demonstrate the bioactive potential of edible cricket peptides, especially as ACE inhibitors.     

免疫性卵巢早衰模型鼠制备的时间

文题释义：免疫性卵巢早衰：近年来卵巢早衰在育龄女性中的发病率逐年上升，且向低龄化发展, 成为女性不孕的常见重要原因之一。卵巢早衰的病因复杂，很多患者(50%-60%)找不到明确的原因，迄今为止卵巢早衰的发病机制不明，临床研究显示10%-30%的卵巢早衰是由免疫因素所致，其早期诊断困难，治疗也相当棘手。因此对于免疫导致卵巢早衰的研究，已成为目前国内外研究的热点。免疫性卵巢早衰模型：免疫性卵巢早衰动物模型的建立为临床研究奠定了基础，因此需要一个建模方法简单，成功率较高，而且卵巢的形态和功能与人类卵巢早衰相似的动物模型。 背景：研究已经证实抗透明带抗体可以加速卵母细胞的破坏和耗竭而致卵巢早衰。 目的：探讨以透明带3多肽(pZP3)诱导BALB/c小鼠建立免疫性的卵巢早衰模型的时间。方法：6-8周龄的健康雌性BALB/c小鼠30只，随机分为免疫实验组(20只)和空白对照组(10只)。实验组小鼠首次免疫注射时间为0周，给予0.15 mL免疫试剂注射双足底及下腹部皮下，每日晨阴道脱落细胞涂片观察小鼠动情周期的变化；2周后给予0.15 mL免疫强化试剂皮下注射相同部位，第4周和第6周的第1天，分别注射免疫试剂或免疫强化试剂各1次(交替注射)。在每次注射前采血用酶联免疫法测小鼠血清性激素；最后观察小鼠卵巢组织及子宫形态。结果与结论：①实验组小鼠初次免疫注射及注射后2周，2组间血清促卵泡生长激素及雌激素水平差异无显著性意义；注射后4周实验组血清雌激素水平明显低于对照组，但促卵泡生长激素水平差异无显著性意义；注射后6周实验组血清雌激素水平明显低于对照组(P < 0.05)，促卵泡生长激素水平明显高于对照组(P < 0.01)；②实验组小鼠卵巢间质纤维化程度较对照组明显，卵巢体积减小，子宫萎缩，小鼠原始卵泡、初级及次级卵泡数均显著低于对照组，闭锁卵泡数量高于对照组(P < 0.05)；③结论：75 μg透明带3多肽诱导BALB/c小鼠，建立自身免疫性卵巢早衰疾病模型，免疫后6周即可达到良好的建模效果。 ORCID: 0000-0001-8035-616X(田海清) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

Endocrine and Metabolic Complications After Bariatric Surgery

Bariatric surgery is the most effective therapeutic option for obese patients; however, it carries substantial risks, including procedure-related complications, malabsorption, and hormonal disturbance. Recent years have seen an increase in the bariatric surgeries performed utilizing either an independent or a combination of restrictive and malabsorptive procedures. We review some complications of bariatric procedures more specifically, hypoglycemia and osteoporosis, the recommended preoperative assessment and then regular follow up, and the therapeutic options. Surgeon, internist, and the patient must be aware of the multiple risks of this kind of surgery and the needed assessment and follow up.