scholarly journals The Role of miR-181c in Mechanisms of Diabetes-Impaired Angiogenesis: An Emerging Therapeutic Target for Diabetic Vascular Complications

2021 ◽  
Vol 12 ◽  
Author(s):  
Emma L. Solly ◽  
Peter J. Psaltis ◽  
Christina A. Bursill ◽  
Joanne T. M. Tan
Keyword(s):  
Signaling Pathways ◽  
Therapeutic Potential ◽  
Unmet Need ◽  
Vascular Complications ◽  
Axonal Guidance ◽  
Diabetic Vascular Complications ◽  
Increased Risk ◽  
Significant Effort ◽  
Impaired Angiogenesis

Diabetes mellitus is estimated to affect up to 700 million people by the year 2045, contributing to an immense health and economic burden. People living with diabetes have a higher risk of developing numerous debilitating vascular complications, leading to an increased need for medical care, a reduced quality of life and increased risk of early death. Current treatments are not satisfactory for many patients who suffer from impaired angiogenesis in response to ischaemia, increasing their risk of ischaemic cardiovascular conditions. These vascular pathologies are characterised by endothelial dysfunction and abnormal angiogenesis, amongst a host of impaired signaling pathways. Therapeutic stimulation of angiogenesis holds promise for the treatment of diabetic vascular complications that stem from impaired ischaemic responses. However, despite significant effort and research, there are no established therapies that directly stimulate angiogenesis to improve ischaemic complications such as ischaemic heart disease and peripheral artery disease, highlighting the immense unmet need. However, despite significant effort and research, there are no established therapies that directly stimulate angiogenesis in a clinical setting, highlighting the immense unmet need. MicroRNAs (miRNAs) are emerging as powerful targets for multifaceted diseases including diabetes and cardiovascular disease. This review highlights the potential role of microRNAs as therapeutic targets for rescuing diabetes-impaired angiogenesis, with a specific focus on miR-181c, which we have previously identified as an important angiogenic regulator. Here we summarise the pathways currently known to be regulated by miR-181c, which include the classical angiogenesis pathways that are dysregulated in diabetes, mitochondrial function and axonal guidance, and describe how these relate both directly and indirectly to angiogenesis. The pleiotropic actions of miR-181c across multiple key angiogenic signaling pathways and critical cellular processes highlight its therapeutic potential as a novel target for treating diabetic vascular complications.

scholarly journals Potential Role of Protein Kinase C in the Pathophysiology of Diabetes-Associated Atherosclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chih-Feng Lien ◽  
Sy-Jou Chen ◽  
Min-Chien Tsai ◽  
Chin-Sheng Lin
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Vascular Complications ◽  
Cellular Responses ◽  
Diabetic Vascular Complications ◽  
Kinase C ◽  
Pkc Activation

Diabetes mellitus is a metabolic syndrome that affects millions of people worldwide. Recent studies have demonstrated that protein kinase C (PKC) activation plays an important role in hyperglycemia-induced atherosclerosis. PKC activation is involved in several cellular responses such as the expression of various growth factors, activation of signaling pathways, and enhancement of oxidative stress in hyperglycemia. However, the role of PKC activation in pro-atherogenic and anti-atherogenic mechanisms remains controversial, especially under hyperglycemic condition. In this review, we discuss the role of different PKC isoforms in lipid regulation, oxidative stress, inflammatory response, and apoptosis. These intracellular events are linked to the pathogenesis of atherosclerosis in diabetes. PKC deletion or treatment with PKC inhibitors has been studied in the regulation of atherosclerotic plaque formation and evolution. Furthermore, some preclinical and clinical studies have indicated that PKCβ and PKCδ are potential targets for the treatment of diabetic vascular complications. The current review summarizes these multiple signaling pathways and cellular responses regulated by PKC activation and the potential therapeutic targets of PKC in diabetic complications.

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

Role of Asymmetric Dimethylarginine (ADMA) in Diabetic Vascular Complications

2008 ◽  
Vol 14 (25) ◽  
pp. 2613-2618 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Seiji Ueda ◽  
Kazuo Nakamura ◽  
Takanori Matsui ◽  
Seiya Okuda
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Vascular Complications ◽  
Diabetic Vascular Complications

The role of a geriatrician in a cancer center.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 39-39 ◽  
Author(s):  
Beatriz Korc-Grodzicki ◽  
Sung W. Sun ◽  
Armin Shahrokni ◽  
Koshy Alexander ◽  
Soo Jung Kim ◽  
...  
Keyword(s):  
Older Adults ◽  
Risk Assessment ◽  
Nurse Practitioners ◽  
Transitional Care ◽  
Unmet Need ◽  
Cancer Center ◽  
Ongoing Research ◽  
Increased Risk

39 Background: Older adults are likely to have coexisting health conditions, polypharmacy and functional limitations. The geriatrician may have a pivotal role in risk assessment, prevention and treatment of comorbidities and addressing geriatric syndromes. The purpose of this study is to describe the growth and development of, and the role of a Geriatrics Service (GS) in a cancer center. Methods: A GS was founded in MSKCC in 2009. Since then it has grown to provide inpatient (IP) and outpatient (OP) care for older adults undergoing cancer diagnosis, surveillance or active treatment. It offers preoperative evaluations, geriatric assessment (GA) and follow-up shared- care. Recently, a Transitional Care Management (TCM) program was established for patients at increased risk of rehospitalization. The GS strives to develop an interprofessional educational geriatrics curriculum and to participate in quality and research projects focused on cancer and aging. Results: Between 2009 and 2014 a total of 6679 new patients were evaluated by the GS. 16% of the patients were 65-75, 70% were 76-85 and 14% were older than 85. 46% were male and 84% were white. 15% were IP and 85% were OP consultations. 13% of the OP consults were for GA, the rest were preoperative evaluations. All patients seen preoperatively who are admitted after surgery, are followed postoperatively by the IP geriatrics team. In total, 4 Geriatricians, 2 Geriatric Nurse Practitioners (GNP) and 3 RNs were recruited. The number of follow-up visits increased from 143 in 2009 to 733 in 2014. The new TCM program based on close communication between the IP and OP GNP has been successful in keeping frail patients from frequent rehospitalizations. Noon conferences on geriatrics for the house staff, a biannual course on “Advancing Nursing Expertise in the Care of Older Adults with Cancer” and a monthly interprofessional meeting for the discussion of Geriatric Clinical Complex Cases (GCCC) are ongoing. Research has focused on risk assessment and the use of telemedicine in geriatric patient care. Conclusions: The establishment of a GS in a cancer center was very well received and embraced by the oncologists showing an unmet need in the care of the older cancer patient. The potential reproducibility beyond the cancer center will be discussed.

scholarly journals Mini-review: diabetic renal complications, a potential stinky remedy

2016 ◽  
Vol 310 (2) ◽  
pp. F119-F122 ◽  
Author(s):  
Utpal Sen ◽  
Sathnur Pushpakumar
Keyword(s):  
Therapeutic Potential ◽  
Vascular Complications ◽  
Vital Role ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Number Of Patients ◽  
Matrix Metabolism ◽  
Artery Disease ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in diabetic patients. Despite optimal management, a significant number of patients progress toward end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini-review highlights the recent findings on the role of H2S in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow-releasing H2S compounds and its therapeutic potential is also included.

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