scholarly journals Conjugates for use in peptide therapeutics: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Ashan Wijesinghe ◽  
Sarika Kumari ◽  
Valerie Booth

While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (# CRD42020222579 ). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.

2020 ◽  
Vol 8 (17) ◽  
pp. 4792-4809
Author(s):  
Irene Lodoso-Torrecilla ◽  
Raquel Klein Gunnewiek ◽  
Eline-Claire Grosfeld ◽  
Rob B. M. de Vries ◽  
Pamela Habibović ◽  
...  

Supplementation of CaP-based bone substitutes with bioinorganics affects biological performance.


Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 633 ◽  
Author(s):  
Catherine Applegate ◽  
Joe Rowles ◽  
John Erdman

First-line therapy for advanced or metastatic prostate cancer (PCa) involves the removal of tumor-promoting androgens by androgen deprivation therapy (ADT), resulting in transient tumor regression. Recurrent disease is attributed to tumor adaptation to survive, despite lower circulating androgen concentrations, making the blockage of downstream androgen signaling a chemotherapeutic goal for PCa. Dietary intake of tomato and its predominant carotenoid, lycopene, reduce the risk for PCa, and preclinical studies have shown promising results that tomato and lycopene can inhibit androgen signaling in normal prostate tissue. The goal of this systematic review was to evaluate whether mechanistic evidence exists to support the hypothesis that tomato or lycopene interact with the androgen axis in PCa. Eighteen studies (n = 5 in vivo; n = 13 in vitro) were included in the final review. A formal meta-analysis was not feasible due to variability of the data; however, the overall estimated directions of effect for the compared studies were visually represented by albatross plots. All studies demonstrated either null or, more commonly, inhibitory effects of tomato or lycopene treatment on androgen-related outcomes. Strong mechanistic evidence was unable to be ascertained, but tomato and lycopene treatment appears to down-regulate androgen metabolism and signaling in PCa.


2020 ◽  
Vol 11 (6) ◽  
pp. 1175-1184 ◽  
Author(s):  
Basil E. Grüter ◽  
Davide Croci ◽  
Salome Schöpf ◽  
Edin Nevzati ◽  
Donato d’Allonzo ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.


Acta Tropica ◽  
2021 ◽  
pp. 106048
Author(s):  
Qiu-Fu Yu ◽  
Jie-Ying Zhang ◽  
Meng-Tao Sun ◽  
Man-Man Gu ◽  
Hui-Ying Zou ◽  
...  

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Bernardo Romão ◽  
Ana Luísa Falcomer ◽  
Gabriela Palos ◽  
Sandra Cavalcante ◽  
Raquel Braz Assunção Botelho ◽  
...  

This study aimed to perform a systematic review and meta-analysis of the glycemic index (GI) of gluten-free bread (GFB) and its main ingredients. The systematic review followed PRISMA guidelines, using seven electronic databases (PubMed, EMBASE, Scopus, Science Direct, Web of Science, gray literature research with Google Scholar, and patents with Google Patent tool), from inception to November 2020. Eighteen studies met the inclusion criteria evaluating 132 GFB samples. Five articles tested GI in vivo, eleven in vitro; and two studies tested both methods. The analysis showed that 60.7% (95% CI: 40.2–78.1%) of the samples presented high glycemic indexes, evidencing a high glycemic profile for GFB. Only 18.2% (95% CI: 11.7–27.2%) of the bread samples presented in the studies were classified as a low GI. Meta-analysis presented moderate/low heterogenicity between studies (I2 = 61% and <1% for both high and low GIs) and reinforced the proportion of high GIs. Lower GIs were found in formulations based on Colocasia esculenta flour or enriched with fiber, yogurt and curd cheese, sourdough, psyllium, hydrocolloids, enzymes, fructans, and resistant starch, highlighting the efficacy of these ingredients to lower GFBs’ GI. GFB tends to present high GI, impacting the development of chronic diseases when consumed.


2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.


Sign in / Sign up

Export Citation Format

Share Document