Том 31, № 2 (2024)
- Год: 2024
- Статей: 8
- URL: https://rjraap.com/0929-8673/issue/view/10039
Anti-Infectives and Infectious Diseases
Meet the Editorial Board Member
127-127
The Importance of Nanocarriers Intra- and Extracellular Degradation: What we Know and Should Know About it?
128-132
Estrogen Receptor and the Gender Bias in Raynauds Phenomenon
133-137
Cognitive Benefits of Sodium-Glucose Co-Transporters-2 Inhibitors in the Diabetic Milieu
Аннотация
Patients with diabetes are at higher risk of cognitive impairment and memory loss than the normal population. Thus, using hypoglycemic agents to improve brain function is important for diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a class of therapeutic agents used in the management of diabetes that has some pharmacologic effects enabling them to fight against the onset and progress of memory deficits. Although the exact mediating pathways are not well understood, emerging evidence suggests that SGLT2 inhibition is associated with improved brain function. This study reviewed the possible mechanisms and provided evidence suggesting SGLT2 inhibitors could ameliorate cognitive deficits.
138-151
A Quinquennial Review of Potent LSD1 Inhibitors Explored for the Treatment of Different Cancers, with Special Focus on SAR Studies
Аннотация
Cancer bears a significant share of global mortality. The enzyme Lysine Specific Demethylase 1 (LSD1, also known as KDM1A), since its discovery in 2004, has captured the attention of cancer researchers due to its overexpression in several cancers like acute myeloid leukaemia (AML), solid tumours, etc. The Lysine Specific Demethylase (LSD1) downregulation is reported to have an effect on cancer proliferation, migration, and invasion. Therefore, research to discover safer and more potent LSD1 inhibitors can pave the way for the development of better cancer therapeutics. These efforts have resulted in the synthesis of many types of derivatives containing diverse structural nuclei. The present manuscript describes the role of Lysine Specific Demethylase 1 (LSD1) in carcinogenesis, reviews the LSD1 inhibitors explored in the past five years and discusses their comprehensive structural activity characteristics apart from the thorough description of LSD1. Besides, the potential challenges, opportunities, and future perspectives in the development of LSD1 inhibitors are also discussed. The review suggests that tranylcypromine derivatives are the most promising potent LSD1 inhibitors, followed by triazole and pyrimidine derivatives with IC50 values in the nanomolar and sub-micromolar range. A number of potent LSD1 inhibitors derived from natural sources like resveratrol, protoberberine alkaloids, curcumin, etc. are also discussed. The structural-activity relationships discussed in the manuscript can be exploited to design potent and relatively safer LSD1 inhibitors as anticancer agents.
152-207
Peptide-based PROTACs: Current Challenges and Future Perspectives
Аннотация
Proteolysis-targeting chimeras (PROTACs) are an attractive means to target previously undruggable or drug-resistant mutant proteins. While small molecule-based PROTACs are stable and can cross cell membranes, there is limited availability of suitable small molecule warheads capable of recruiting proteins to an E3 ubiquitin ligase for degradation. With advances in structural biology and in silico protein structure prediction, it is now becoming easier to define highly selective peptides suitable for PROTAC design. As a result, peptide-based PROTACs are becoming a feasible proposition for targeting previously "undruggable" proteins not amenable to small molecule inhibition. In this review, we summarize recent progress in the design and application of peptide-based PROTACs as well as several practical approaches for obtaining candidate peptides for PROTACs. We also discuss the major hurdles preventing the translation of peptide-based PROTACs from bench to bedside, such as their delivery and bioavailability, with the aim of stimulating discussion about how best to accelerate the clinical development of peptide- based PROTACs in the near future.
208-222
Efficacy and Safety of Alirocumab and Evolocumab as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors in Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis
Аннотация
Background:Familial hypercholesterolemia (FH) is a prevalent and potentially fatal illness that causes a substantial elevation in low-density lipoprotein cholesterol (LDL-C).
Methods:A comprehensive search was done on PubMed/MEDLINE, EMBASE, Web of Science (WOS/ ISI), Scopus, ClinicalTrials (www.ClinicalTrials.gov), and conferences/ congress research papers. Random effect models were used to calculate mean differences (%) and risk ratios (RRs), and confidence intervals (95%).
Results:Ten studies (n=1489 patients) were included in this study. PCSK9 inhibitors decreased the levels of LDL-C by -49.59% (95%CI -55.5%, -43.67%) as compared to placebo. They also didnt alter the Treatment-Emergent Adverse Event (TEAE) and neuronal events by RR 0.92 (0.75, 1.13) and 1.31 (0.66, 2.59), respectively. PCSK9 inhibitors were effective and safe in treating patients with FH.
Conclusion:There was high-quality evidence showing that monoclonal antibodies (alirocumab & evolocumab) lower LDL-C (GRADE: high), lipoprotein (a) (GRADE: High), triglycerides (TG) (GRADE: High), total cholesterol (GRADE: High), non-high-density lipoprotein cholesterol (non- HDL-C) (GRADE: Moderate), and apolipoprotein B (GRADE: High), and increase the HDL-C (GRADE: High) as well as apolipoprotein A1 (GRADE: High). Comparing PCSK9 inhibitors against placebo, neither TEAE (GRADE: high) nor neuronal events (GRADE: moderate) were changed.
Registration number:PROSPERO-CRD42022334035
223-241
Resveratrol Inhibits Restenosis through Suppressing Proliferation, Migration and Trans-differentiation of Vascular Adventitia Fibroblasts via Activating SIRT1
Аннотация
Aim:After the balloon angioplasty, vascular adventitia fibroblasts (VAFs), which proliferate, trans-differentiate to myofibroblasts and migrate to neointima, are crucial in restenosis. Resveratrol (RSV) has been reported to protect the cardiovascular by reducing restenosis and the mechanism remains unclear.
Methods:This study was dedicated to investigate the effect of RSV on VAFs in injured arteries and explore the potential mechanism. In this work, carotid artery balloon angioplasty was performed on male SD rats to ensure the injury of intima and VAFs were isolated to explore the effects in vitro. The functional and morphological results showed the peripheral delivery of RSV decreased restenosis of the injured arteries and suppressed the expression of proliferation, migration and transformation related genes. Moreover, after being treated with RSV, the proliferation, migration and trans-differentiation of VAFs were significantly suppressed and exogenous TGF-β1 can reverse this effect.
Result:Mechanistically, RSV administration activated SIRT1 and decreased the translation and expression of TGF-β1, SMAD3 and NOX4, and reactive oxygen species (ROS) decreased significantly after VAFs treated with RSV.
Conclusion:Above results indicated RSV inhibited restenosis after balloon angioplasty through suppressing proliferation, migration and trans-differentiation of VAFs via regulating SIRT1- TGF-β1-SMAD3-NOX4 to decrease ROS.
242-256