ATP-binding cassette (ABC) transporters are membrane-spanning proteins involved in cholesterol homeostasis, transport of various molecules in and out of cells and organelles, oxidative stress, immune recognition, and drug efflux. They are long implicated in the development of multidrug resistance in cancer chemotherapy. Existing clinical and molecular evidence has also linked ABC transporters with cancer pathogenesis, prognostics, and therapy. In this review, we aim to provide a comprehensive update on all ABC transporters and their roles in drug resistance in breast cancer (BC). For solid tumours such as BC, various ABC transporters are highly expressed in less differentiated subtypes and metastases. ABCA1, ABCB1 and ABCG2 are key players in BC chemoresistance. Restraining these transporters has evolved as a possible mechanism to reverse this phenomenon. Further, ABCB1 and ABCC1 are important in BC prognosis. Newer therapeutic approaches have been developed to target all these molecules to dysregulate their effect, reduce cell viability, induce apoptosis, and increase drug sensitivity. In the future, targeted therapy for specific genetic variations and upstream or downstream molecules can help improve patient prognosis.

Multiple sclerosis (MS), a subset of chronic primary inflammatory demyelinating disorders of the central nervous system, is closely associated with various movement disorders. These disorders may be due to MS pathophysiology or be coincidental. This review describes the full spectrum of movement disorders in MS with their possible mechanistic pathways and therapeutic modalities. The authors conducted a narrative literature review by searching for ‘multiple sclerosis’ and the specific movement disorder on PubMed until October 2021. Relevant articles were screened, selected, and included in the review according to groups of movement disorders. The most prevalent movement disorders described in MS include restless leg syndrome, tremor, ataxia, parkinsonism, paroxysmal dyskinesias, chorea and ballism, facial myokymia, including hemifacial spasm and spastic paretic hemifacial contracture, tics, and tourettism. The anatomical basis of some of these disorders is poorly understood; however, the link between them and MS is supported by clinical and neuroimaging evidence. Treatment options are disorder-specific and often multidisciplinary, including pharmacological, surgical, and physical therapies. Movements disorders in MS involve multiple pathophysiological processes and anatomical pathways. Since these disorders can be the presenting symptoms, they may aid in early diagnosis and managing the patient, including monitoring disease progression. Treatment of these disorders is a challenge. Further work needs to be done to understand the prevalence and the pathophysiological mechanisms responsible for movement disorders in MS.

Background: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies are essential. Introduction: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic posttranscriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). Methods: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. Results: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as low-grade inflammation. Conclusion: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.

Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that antagonizes the proto-oncogenic phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and governs basic cellular metabolic processes. Recently, its role in cell growth, metabolism, architecture, and motility as an intramolecular and regulatory mediator has gained widespread research interest as it applies to non-tumorous diseases, such as insulin resistance (IR) and diabetic nephropathy (DN). DN is characterized by renal tubulointerstitial fibrosis (TIF) and epithelial-mesenchymal transition (EMT), and PTEN plays a significant role in the regulation of both. Epigenetics and microRNAs (miRNAs) are novel players in post-transcriptional regulation and research evidence demonstrates that they reduce the expression of PTEN by acting as key regulators of autophagy and TIF through activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway. These regulatory processes might play an important role in solving the complexities of DN pathogenesis and IR, as well as the therapeutic management of DN with the help of PTEN K27-linked polyubiquitination. Currently, there are no comprehensive reviews citing the role PTEN plays in the development of DN and its regulation via miRNA and epigenetic modifications. The present review explores these facets of PTEN in the pathogenesis of IR and DN.

Growth differentiation factor-15 (GDF-15) is a novel cytokine secreted by a variety of cells like macrophages, adipocytes, normally expressed in high amounts by placenta. It is also highly expressed in multiple carcinomas like Colon, Breast, Pancreas, Liver, and Ovarian. Several reports on serum GDF-15 as a potential biomarker for diagnosis and prognosis of cancer are hampered by the lack of robust data, with large sample size and critical patient recruitment. However, experimental accounts on cancer tumors, cell lines, and animal models suggest GDF-15’s role in cancer progression via endothelial mesenchymal transition, angiogenesis, metastasis, drug resistance and even stemness of various cancers. GDF-15 could be the point of amalgamation for the various hallmarks of cancer and can prove a useful therapeutic target in cancer. The current review was conceptualized with a thought of critically appraising the existing information of GDF-15 in carcinogenesis.