Current Protein and Peptide Science - Volume 24, Issue 9, 2023

Studies have shown that injection of recombinant angiotensin-converting enzyme 2 (ACE2) significantly increased circulatory levels of ACE2 activity, reduced cardiac hypertrophy and fibrosis, and effectively lowered blood pressure. In addition, recombinant ACE2 ameliorated albuminuria and might contribute to renal protection. Meanwhile, potential pharmacological treatments based on ACE2 are attracting increasing attention from scientists following a growing understanding of the role of the ACE2 receptor in the pathogenesis of coronavirus disease 2019 (COVID-19). In this article, we comprehensively summarized the literature on the structure, distribution, and function of ACE2. More importantly, we draw a conclusion that ACE2 decoys such as sACE2, hrsACE2 and ACE2-derived peptides, drugs down-regulating the ACE2 or TMPRSS2 gene expression, and the application of epigenetic modifiers and Traditional Chinese Medicine might represent promising approaches for the future of COVID-19 treatment.

Biotechnologists have pioneered the idea of an edible vaccination in recent years. Subunit vaccines, such as those used to create edible vaccines, involve the introduction of certain genes into transgenic plants, which are subsequently coaxed into producing the corresponding protein. Bananas, potatoes, legumes, lettuce, soybeans, corn, and rice are all examples of foods that fall under this category. They have a low unit cost, can be stored conveniently, and are simple to administer to patients of varying ages. There is great hope that the use of edible vaccinations, particularly in underdeveloped countries, could drastically reduce the prevalence of diseases, including measles, cholera, hepatitis B, and diarrhea. The development of effective and widely applicable edible vaccination, however, faces a number of technological and regulatory hurdles. When compared to traditional immunizations, edible vaccines offer significant cost savings, increased productivity, and reduced risk. It raises the possibility of a more efficient approach to illness prevention. This article includes important uses, production, host plants, benefits, drawbacks, mechanism of action, and many regulatory difficulties related to edible vaccines. In this article, we have discussed the most recent developments and successes with edible and intradermal vaccines in terms of the system used for immunogen production, the molecular properties of these vaccines, and their ability to generate a protective systemic and mucosal response.

The current studies show signs of progress in treating Alzheimer's disease (AD) with the “brain-gut axis.” Restoring intestinal flora balance can alleviate neurodegeneration in the central nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective mechanism brought by intestinal flora has not been fully understood. Trimethylamine N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile, all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated. Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia, etc., correlate with the production process of TMAO. High choline intake and insulin resistance have also been identified as contributors to TMAO synthesis. With the increasing TMAO in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1, SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important pathological factor of AD.

Background: LncRNAs have been corroborated to exert crucial effects in malignancies, including laryngeal squamous cell carcinoma (LSCC). Nevertheless, the role and mechanism of EPB41L4A- AS2 in LSCC are inadequately investigated and warrant further exploration. Methods: Relevant database was adopted to analyze the relationship between EPB41L4A-AS2 expression level and tumors. The expressions and relationships of EPB41L4A-AS2, RE-1 silencing transcription factor (REST), miR-1254, and homeodomain interacting protein kinase 2 (HIPK2) in LSCC cells were evaluated by qRT-PCR, Pearson’s correlation tests, RNA immunoprecipitation, RNA pull-down assay, chromatin immunoprecipitation, database, and dual-luciferase reporter assay. Following the required transfection, the biological behaviors of LSCC cells were examined using cell function experiments. Meanwhile, the levels of Ki-67 and apoptosis-, and epithelial-mesenchymal transition (EMT) pathway-related proteins were quantified with Western blot. Moreover, xenografts in nude mice were constructed, and the tumor volume and weight were measured. Ki-67 positivity was determined by immunohistochemical staining. Results: EPB41L4A-AS2 and HIPK2 were lower-expressed, yet miR-1254 and REST were higher- expressed in LSCC cells. Pearson’s correlation assay results exhibited a positive correlation between HIPK2 and EPB41L4A-AS2 and a negative correlation between HIPK2 and miR-1254. Overexpressed EPB41L4A-AS2 diminished the biological behavior, and repressed the levels of Ki-67 and EMT-related markers in LSCC cells whilst enhancing those of apoptosis-related markers. These aforementioned effects were counteracted by miR-1254 mimic. Moreover, EPB41L4A- AS2 overexpression suppressed the growth of tumors and reduced the positive expression of Ki-67 in nude mice. Besides, miR-1254 aggravated the biological behaviors and elevated the levels of Ki-67 and EMT-related proteins in LSCC cells while reducing the levels of apoptosis-related markers via targeting HIPK2. Conclusion: REST-restrained EPB41L4A-AS2 modulates LSCC development via regulating miR-1254/HIPK2 pathway.

Aims: Identify novel tyrosinase inhibitory peptides from sea cucumber (Apostichopus japonicus) collagen using in silico methods and elucidate the molecular interaction mechanism. Background: Tyrosinase is a key enzyme in the melanin biosynthesis pathway, to restrain melanin production and reduce the appearance of associated skin diseases, inhibition of tyrosinase activity is one of the most effective methods. Objective: The collagen from Apostichopus japonicus, which consists of 3,700 amino acid residues, was obtained from the National Center for Biotechnology Information (NCBI) as the accession number of PIK45888. Method: Virtual hydrolyzed method was used, and the peptides generated were compared to the previously established BIOPEP-UWM database. In addition, peptides were examined for their solubility, toxicity, and tyrosinase-binding capacity. Result: A tripeptide CME with optimal potential inhibitory activity against tyrosinase was identified, and its inhibitory activity was validated by in vitro experiments. The IC50 value of CME was 0.348 ± 0.02 mM for monophenolase, which was inferior to the positive control peptide glutathione, while it had an IC50 value of 1.436 ± 0.07 mM for diphenolase, which was significantly better than glutathione, and the inhibition effect of CME on tyrosinase was competitive and reversible. Conclusion: In silico methods were efficient and useful in the identification of new peptides.

Aims: The role of SNHG4 in the initiation and development of gastric cancer. Background: Gastric cancer is one of the leading causes of cancer death worldwide. Studies have shown that lncRNAs have a regulatory function in human diseases, particularly cancers. Small nuclear RNA host gene 4 (SNHG4) has been known as an oncogenic long noncoding RNA (lncRNA) in various cancers, and its dysregulation can lead to tumorigenesis and cancer progression. Objective: Alteration of SNHG4 expression in gastric cancer and its correlation with clinical features of patients with stomach cancer; also, the accomplishment of bioinformatic analysis to find the potential pathways which could be impressed by changes in SNHG4 RNA expression. Methods: The present study aims to determine the molecular mechanism of SNHG4 and the effects of its expression on the development of GC. Based on the bioinformatics investigations, we studied gene expression analysis, Kaplan-Meier survival, Gene ontology (GO), KEGG pathway enrichment, microRNA targets, transcription factor targets, and proteins interacting with SNHG4. During the experimental phase, SNHG4 expression was examined by quantitative real-time PCR (qRTPCR) in 40 paired gastric adenocarcinoma tissues and normal neighboring tissues. Also, we investigated the correlation between SNHG4 expression and patients' clinicopathological characteristics. Results: Increased SNHG4 expression was detected in GC tissues, which is significantly associated with the TNM stage, grade group, tumor size, and metastatic status. Evaluation survival analysis demonstrated that overexpression of SNHG4 in GC tissues is remarkably related to poor overall survival (OS). SNHG4 is closely related to miR-490 and E2F family transcription factors. GO analysis suggested the possible role of SNHG4 in cell-cell adhesion, and KEGG enrichment analysis revealed that SNHG4 could be associated with the gastric cancer signaling pathway. ELAVL1 and IGF2BP2 have the highest number of SNHG4 target sites, and these proteins are involved in the PI3K-Akt-mTOR and ERK-MAPK signaling pathways. Conclusion: Based on our results, we conclude that SNHG4 may have a function in GC development by regulating tumor-related signaling pathways.