scholarly journals Optimal therapeutic adropin dose intervention in mice and rat animal models: A systematic review

2021 ◽  
pp. 1426-1429
Author(s):  
Foad Alzoughool ◽  
Mohammad Borhan Al-Zghoul

Background and Aim: Adropin is a hormone encoded by the Enho gene, which is associated with energy homeostasis. Preclinical studies using animal models have shown that adropin plays a role in enhancing glucose homeostasis and dyslipidemia. Lately, several studies on animal models have been performed to examine the therapeutic and pathophysiological effects of adropin in many disorders. The aim of this systematic review was to identify the ideal adropin dose in mice and rat animal models. Materials and Methods: We systematically searched PubMed, Science Direct, and Scopus databases from 2008 to 2020. The terms used in the search were "adropin," "adropin doses in animal models," "glucose homeostasis related to adropin," and "adropin therapeutic effects on rats and mice." Articles that included non-adropin doses, in vitro studies, and factors affecting adropin levels were excluded from the study. Results: Of the total 179 qualified studies, six studies were included. We found that a daily injection of 450 nmol/kg of adropin for 3 days might be considered the optimum dose of effect in mice, whereas injection of 2.1 μg/kg once a day for 10 successive days might be the optimal effective dose in rats. Conclusion: Additional investigations are needed to determine the optimum dose of adropin to be used as a therapeutic intervention depending on the animal model.

2020 ◽  
Vol 13 (10) ◽  
pp. 2191-2196
Author(s):  
Foad Alzoughool ◽  
Mohammad Borhan Al-Zghoul ◽  
Saad Al-Nassan ◽  
Lo'ai Alanagreh ◽  
Dana Mufleh ◽  
...  

Background and Aim: Irisin, a novel myocyte-secreted hormone, was proposed to mediate some of the beneficial effects of exercise such as browning of adipocytes, thermogenesis, and metabolic homeostasis. Recently, several animals' models' studies have been performed to investigate the therapeutic impact of irisin in several disorders. Several interventional trials used different doses. However, optimum dose was not determined. This systematic review aims to identify the optimal dose of interventional irisin in mice and rat animal models. Materials and Methods: Online databases PubMed, Google Scholar, and Springer were systematically searched from 2012 to 2019. The words searched were irisin, irisin and animal model, physical activity, and irisin and irisin dosage. Non-irisin doses, in vitro studies, and factors influencing irisin levels were excluded. Results: Eleven of the total 391 qualifying studies were included. A daily injection of 500 μg/kg irisin may be the optimum dose of effect in mice and rats. Conclusion: More studies are required to determine the optimum dose of irisin to be used as a therapeutic intervention based on animal model.


2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.


2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.


2020 ◽  
Author(s):  
Zhao Yixiu ◽  
Xinhui Wang ◽  
Shuang Yang ◽  
Xia Song ◽  
Chao Chen ◽  
...  

Abstract Background: Diabetic wounds (DWs), especially leg or foot ulcers, are common diabetic complications, accounting for about 20% of diabetic patients. At present, there is still lack of effective measures to treat DWs in clinical practice. Kanglexin (KLX) is an anthraquinone compound with vasoprotective effect. This study will explore the therapeutic effects of KLX on DWs and the underlying mechanisms.Method: KM mice were injected with streptozocin (180 mg/kg) intraperitoneally to establish animal model of Type 1 Diabetes. The full-thickness skin wounds with the diameter of 5 mm were prepared on the back of diabetic mice with a skin punch. KLX is dissolved in sterile injection oil and applied to the wound once a day for 14 consecutive days. The wounds were photographed every day and the wound size was analyzed by Image Pro Plus software. On the 3rd, 7th, 11th day after KLX administration, skin tissues with a diameter of 1cm around the wound were fixed in paraformaldehyde and subjected to HE, Masson and immunohistochemical staining. Collagen deposition were evaluated by hydroxyproline kit. Angiogenesis of wound skin was evaluated by recording the formation of new blood vessels on its subsurface. In vitro study, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs, 100 μg/mL) to establish the cell model of DWs. The proliferation, migration and tubular structure formation of HUVECs were measured by MTT, scratch and tubule formation experiments, respectively. Phosphorylation of ERK1/2 was detected by Western blot analysis.ResultsFirstly, in-vivo study showed that KLX significantly accelerated the closure of diabetic wounds through promoting granulation tissue formation, collagen synthesis and angiogenesis. Secondly, in vitro study results further confirmed that KLX promoted the proliferation, migration and tubular structure formation of HUVECs. Besides, KLX significantly up-regulated phospho-ERK1/2 both in diabetic wounds and AGEs-treated HUVECs. Thirdly, molecular docking simulation results indicated that there were multiple hydrogen bonds between KLX and FGFR amino acid residues, and FGFR inhibitor PD173074 significantly reversed KLX’s promotion of ERK1/2 phosphorylation and angiogenesis. Conclusions:KLX promotes angiogenesis and accelerates the healing of diabetic wounds by activating FGFR and ERK1/2 signaling pathway.


2021 ◽  
Author(s):  
ling wang ◽  
yang yu ◽  
cong zhou ◽  
run wan ◽  
Yumin Li

Abstract Background and objectives: Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Several preclinical and clinical studies have examined the potential of repurposing disulfiram (DSF) as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans.Methods: Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics.Results: Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule.Conclusions: This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.


2020 ◽  
Vol 117 (24) ◽  
pp. 13428-13436 ◽  
Author(s):  
Colin G. Buss ◽  
Sangeeta N. Bhatia

The recent advent of immune checkpoint inhibitor (CPI) antibodies has revolutionized many aspects of cancer therapy, but the efficacy of these breakthrough therapeutics remains limited, as many patients fail to respond for reasons that still largely evade understanding. An array of studies in human patients and animal models has demonstrated that local signaling can generate strongly immunosuppressive microenvironments within tumors, and emerging evidence suggests that delivery of immunostimulatory molecules into tumors can have therapeutic effects. Nanoparticle formulations of these cargoes offer a promising way to maximize their delivery and to enhance the efficacy of checkpoint inhibitors. We developed a modular nanoparticle system capable of encapsulating an array of immunostimulatory oligonucleotides that, in some cases, greatly increase their potency to activate inflammatory signaling within immune cells in vitro. We hypothesized that these immunostimulatory nanoparticles could suppress tumor growth by activating similar signaling in vivo, and thereby also improve responsiveness to immune checkpoint inhibitor antibody therapies. We found that our engineered nanoparticles carrying a CpG DNA ligand of TLR9 can suppress tumor growth in several animal models of various cancers, resulting in an abscopal effect on distant tumors, and improving responsiveness to anti-CTLA4 treatment with combinatorial effects after intratumoral administration. Moreover, by incorporating tumor-homing peptides, immunostimulatory nucleotide-bearing nanoparticles facilitate antitumor efficacy after systemic intravenous (i.v.) administration.


2016 ◽  
Vol 36 (19) ◽  
pp. 2440-2450 ◽  
Author(s):  
Yaohua Hu ◽  
William G. Robichaux ◽  
Fang C. Mei ◽  
Eun Ran Kim ◽  
Hui Wang ◽  
...  

Epacs (exchange proteins directly activated by cyclic AMP [cAMP]) act as downstream effectors of cAMP and play important roles in energy balance and glucose homeostasis. While global deletion of Epac1 in mice leads to heightened leptin sensitivity in the hypothalamus and partial protection against high-fat diet (HFD)-induced obesity, the physiological functions of Epac1 in white adipose tissue (WAT) has not been explored. Here, we report that adipose tissue-specific Epac1 knockout (AEKO) mice are more prone to HFD-induced obesity, with increased food intake, reduced energy expenditure, and impaired glucose tolerance. Despite the fact that AEKO mice on HFD display increased body weight, these mice have decreased circulating leptin levels compared to their wild-type littermates.In vivoandin vitroanalyses further reveal that suppression of Epac1 in WAT decreases leptin mRNA expression and secretion by inhibiting cAMP response element binding (CREB) protein and AKT phosphorylation, respectively. Taken together, our results demonstrate that Epac1 plays an important role in regulating energy balance and glucose homeostasis by promoting leptin expression and secretion in WAT.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2532
Author(s):  
Ludovica Bartiromo ◽  
Matteo Schimberni ◽  
Roberta Villanacci ◽  
Jessica Ottolina ◽  
Carolina Dolci ◽  
...  

The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.


Author(s):  
Zahra Zahedi-Tabar ◽  
Shadab Bagheri-Khoulenjani ◽  
Saeid Amanpour ◽  
Hamid Mirzadeh

Hyperthermia is a novel method for cancer therapy. To have the best control when heating tissues in hyperthermia, the use of magnetic nanoparticles is suggested. The local control of heat is very important in this technique, to prevent the damage of healthy tissues around the tumor, and therefore it is necessary to measure changes in temperature to determine the optimum conditions in which hyperthermia can create the desired results. The type and concentration of nanoparticles and nanoparticle distribution within the cancerous tissue are key factors affecting temperature distribution throughout the hyperthermia process. One of the main factors influencing nanoparticle distribution is the characteristics of the diffusion media, such as chemical composition, morphological and mechanical features, all of which affect the diffusion of nanoparticles at the cancer site. In this review, the most common in vitro and in vivo media and their influence on the results of hyperthermia are discussed. We also mention in silico as a computational model. Buffer solutions, cell cultures, microfluids, dead tissues and animal models are some of the in vitro media that are discussed in this review paper. In addition, some of the animal models used for hyperthermia will be mentioned.


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