PMID- 32470453 OWN - NLM STAT- MEDLINE DCOM- 20200629 LR - 20200629 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 255 DP - 2020 Aug 15 TI - The impact of metformin and aspirin on T-cell mediated inflammation: A systematic review of in vitro and in vivo findings. PG - 117854 LID - S0024-3205(20)30604-4 [pii] LID - 10.1016/j.lfs.2020.117854 [doi] AB - Chronic inflammation and hyperglycaemia are well-established aspects in the pathogenesis of type 2 diabetes mellitus (T2D), including the progression of its associated complications such as cardiovascular diseases (CVDs). In fact, emerging evidence shows that dysfunctional immune responses due to dysregulated T-cell function aggravates CVD-related complications in T2D. However, there is a lack of specific therapeutic interventions that protect patients with diabetes who are at risk of heart failure. Metformin and aspirin are among the leading therapies being used to protect or at the very least slow the progression of CVD-related complications. The current review made use of major electronic databases to identify and systematically synthesise emerging experimental data on the impact of these pharmacological drugs on T-cell responses. The quality and risk of bias of include evidence were independently assessed by two reviewers. Overwhelming evidence showed that both metformin and aspirin can ameliorate T-cell mediated inflammation by inducing regulatory T-cells (Tregs) polarisation, inhibiting T-cell trafficking and activation as well as signal transducer and activator of transcription (STAT)3 signalling. As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways. Whilst aspirin modulated nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and co-stimulatory signalling pathways and induced T-cell anergy. Overall, synthesised data prompt further investigation into the combinational effect of metformin and aspirin for the management of T2D-related cardiovascular complications. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Nyambuya, Tawanda Maurice AU - Nyambuya TM AD - School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; Department of Health Sciences, Faculty of Health and Applied Sciences, Namibia University of Science and Technology, Windhoek, Namibia. Electronic address: mnyambuya@nust.na. FAU - Dludla, Phiwayinkosi Vusi AU - Dludla PV AD - Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy. Electronic address: pdludla@mrc.ac.za. FAU - Mxinwa, Vuyolwethu AU - Mxinwa V AD - School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: 218081787@stu.ukzn.ac.za. FAU - Mokgalaboni, Kabelo AU - Mokgalaboni K AD - School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: 218086707@stu.ukzn.ac.za. FAU - Ngcobo, Siphamandla Raphael AU - Ngcobo SR AD - School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: 213514766@stu.ukzn.ac.za. FAU - Tiano, Luca AU - Tiano L AD - Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy. Electronic address: l.tiano@staff.univpm.it. FAU - Nkambule, Bongani Brian AU - Nkambule BB AD - School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: nkambuleb@ukzn.ac.za. LA - eng PT - Journal Article PT - Systematic Review DEP - 20200526 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - R16CO5Y76E (Aspirin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/pharmacology MH - Aspirin/administration & dosage/*pharmacology MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Drug Therapy, Combination MH - Humans MH - Hypoglycemic Agents/administration & dosage/pharmacology MH - Inflammation/*drug therapy/pathology MH - Metformin/administration & dosage/*pharmacology MH - T-Lymphocytes/immunology OTO - NOTNLM OT - Aspirin OT - Cardiovascular diseases OT - Inflammation OT - Metabolic diseases OT - Metformin OT - T-cells OT - Type 2 diabetes mellitus COIS- Declaration of competing interest Authors declare that they have no conflict of interest. EDAT- 2020/05/30 06:00 MHDA- 2020/07/01 06:00 CRDT- 2020/05/30 06:00 PHST- 2020/05/11 00:00 [received] PHST- 2020/05/25 00:00 [accepted] PHST- 2020/05/30 06:00 [pubmed] PHST- 2020/07/01 06:00 [medline] PHST- 2020/05/30 06:00 [entrez] AID - S0024-3205(20)30604-4 [pii] AID - 10.1016/j.lfs.2020.117854 [doi] PST - ppublish SO - Life Sci. 2020 Aug 15;255:117854. doi: 10.1016/j.lfs.2020.117854. Epub 2020 May 26.