Archives of internal medicine research最新文献

{"title":"Epidemiology, Pathogenesis, Clinical Manifestations, and Management Strategies of Tuberculous Meningitis.","authors":"Nicholas Oo, Devendra K Agrawal","doi":"10.26502/aimr.0195","DOIUrl":"10.26502/aimr.0195","url":null,"abstract":"<p><p>Tuberculous meningitis (TBM), the most severe manifestation of extrapulmonary tuberculosis, poses significant global health challenges due to its high mortality rates and complex pathophysiology. This review synthesizes recent findings on TBM, covering epidemiology, pathogenesis, clinical manifestations, diagnostics, and management strategies. TBM disproportionately affects immunocompromised populations, including individuals with HIV, with the highest mortality observed in low-resource settings. Pathogenesis involves Mycobacterium tuberculosis breaching the blood-brain barrier, eliciting a granulomatous inflammatory response that contributes to neurotoxicity. Advances in diagnostics, such as next-generation sequencing and novel imaging techniques, have improved early detection and treatment guidance. Management strategies emphasize multidrug regimens, adjunctive corticosteroids, and emerging therapies like intrathecal administration and nanoparticle-based drug delivery. Host-directed therapies targeting immune modulation and oxidative stress show promise in improving outcomes, particularly for drug-resistant TBM. Despite advancements, diagnostic delays, treatment resistance, and high rates of neurological effects underscore the need for further research. Preventive strategies focusing on early diagnosis, modifiable risk factor management, and public health interventions are critical to reducing global burden of TBM. This review highlights the importance of integrating innovative diagnostics, tailored treatments, and preventive measures to address the challenges of TBM and improve patient outcomes.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"8 1","pages":"48-58"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Underlying Failure of Methotrexate Treatment in Rheumatoid Arthritis: Implications in Personalized Care.","authors":"Ananta Srivastava, Stefanie Au, Sumanjali Reddy Kanmantha Reddy, Emmanuel Katsaros, Devendra K Agrawal","doi":"10.26502/aimr.0203","DOIUrl":"10.26502/aimr.0203","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory disease that can be managed with a range of therapeutic treatments. Methotrexate (MTX) is a first-line treatment for RA; however, its metabolism in RA patients can be complicated by multiple factors. Therefore, understanding these specific factors is crucial for optimizing the efficacy of MTX to provide improved therapeutic outcomes for patients. This article explores existing literature to examine how MTX metabolism in RA patients is impacted by other commonly used medications for RA. Additionally, the review explores the role of genetics by investigating the impact that single nucleotide polymorphisms (SNPs) have on MTX metabolism. Key findings from this review highlight how MTX metabolism can be enhanced or impaired based on specific combination therapies and how alternative treatments are considered with MTX treatment failure. MTX metabolism can also vary across different racial, ethnic, and population-based groups due to the presence of distinct SNPs in their genetic profiles. These results underscore the importance of personalized treatment approaches when treating RA patients with MTX, as its metabolism is influenced by factors such as drug interactions and SNPs. Future research is needed to expand our understanding of these factors to further improve therapeutic outcomes in RA patients.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"8 2","pages":"121-131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Pathogenesis to Fall Risk in Multiple Sclerosis.","authors":"Jaylan Patel, Marcel P Fraix, Devendra K Agrawal","doi":"10.26502/aimr.0194","DOIUrl":"10.26502/aimr.0194","url":null,"abstract":"<p><p>Multiple Sclerosis is a chronic neurological disorder characterized by progressive disability, with falls being a significant consequence of its physical and cognitive impairments. This review explores the major contributors to fall risk in individuals with multiple sclerosis and explores the broader implications of these factors, such as the fear of falling. The primary factors associated with fall risk include gait abnormalities, cognitive dysfunction, and fatigue. These factors often interact, leading to mobility limitations and diminishing overall quality of life. Interventions to mitigate fall risk in multiple sclerosis have shown varying degrees of success. Exercise and rehabilitation strategies improve physical function and balance, while cognitive-behavioral therapy addresses fatigue and associated symptoms. Self-management programs empower patients to take an active role in symptom management, though their effectiveness varies. Disease-modifying therapies are the primary treatment for slowing disease progression, indirectly reducing fall risk. Emerging technologies show promise in enhancing mobility and safety, while machine learning algorithms offer the potential for predicting fall risk in multiple sclerosis populations. This review underscores the need for a comprehensive approach to fall prevention in multiple sclerosis. Healthcare providers can develop personalized strategies to improve mobility, reduce fall incidence, and enhance the quality of life for individuals with multiple sclerosis. Further research is essential to refine these interventions and optimize long-term outcomes.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"8 1","pages":"36-47"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide: Double-edged Sword with Risks and Benefits.","authors":"Lekha Pillarisetti, Devendra K Agrawal","doi":"10.26502/aimr.0189","DOIUrl":"10.26502/aimr.0189","url":null,"abstract":"<p><p>Type 2 Diabetes Mellitus therapy has evolved over the years to now include a new class of therapeutics, semaglutide. This article reviews the mechanism of action and formulation of semaglutide therapy, potential benefits, contraindications, adverse effects, and drug interactions. Oral and subcutaneous semaglutide therapies have shown effectiveness in improving glycemic control, weight loss, and reducing cardiovascular risks associated with diabetes mellitus. Semaglutide has also shown potential in being used as a therapeutic strategy in Alzheimer's disease due to its anti-neuroinflammatory effects and being used to treat polycystic ovary syndrome. However, semaglutide therapy is also associated with concerning adverse effects like acute pancreatitis, anesthetic risks like pulmonary aspiration or residual gastric content, acute kidney injury, acute gallbladder injury, nonarteritic anterior ischemic optic neuropathy and diabetic retinopathy. Contraindications of semaglutide include history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and pregnancy. Drug interactions to consider with semaglutide therapy include those also used in diabetes treatment, like metformin, as well as anti-psychotics, due to anti-psychotics associated weight gain. The findings of this article emphasize the need for a cross-disciplinary approach to understand the molecular mechanisms and clinical implications of semaglutide on patients with complex medical histories and treatment regimens. The potential anesthetic risks of semaglutide therapy warrant careful consideratiion with ethical concerns. Further studies can assess if there is a need to modify pre-operative guidelines to account for patient using semaglutide and how delayed gastric emptying and constitpation will affect surgical outcomes and complications. While semaglutide therapy for diabetes mellitus has been established, there is a need for extensive research on repurposing semaglutide in neurodegenerative disease treatment.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"8 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifestyle Factors in the Clinical Manifestation and Management of Atopic Dermatitis.","authors":"Kelly Lam, Devendra K Agrawal","doi":"10.26502/aimr.0193","DOIUrl":"10.26502/aimr.0193","url":null,"abstract":"<p><p>Atopic dermatitis (AD), also known as eczema, is an inflammatory dermatologic condition that results in inflamed, itchy skin lesions. The development of this condition is governed by a variety of genetic and environmental factors including lifestyle habits. The severity of atopic dermatitis has been attributed to be affected by various lifestyle factors, prompting the interest in utilizing lifestyle modifications as a form of treatment for atopic dermatitis symptoms. Many research studies have been conducted to investigate the effects of different factors such as sleep, stress, diet, smoking and tobacco use, exposure to various temperatures and humidity levels, and skincare and cosmetic products on atopic dermatitis symptoms, and how certain habits can be modified to manage AD conditions. Current studies have demonstrated the significant impact some lifestyle modifications can elicit with improving atopic dermatitis, while also discussing other lifestyle factors that require further research to determine their effects on AD. This review article summarizes the findings in the current literature that investigates the role of different lifestyle habits on the severity and exacerbation of atopic dermatitis, and explores the mechanisms in which these behaviors can trigger AD.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"8 1","pages":"25-35"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid Insensitivity in Severe Asthma: Underlying Molecular Mechanisms, Challenges, and Emerging Therapies.","authors":"Chang Kon Kim, Devendra K Agrawal","doi":"10.26502/aimr.0202","DOIUrl":"https://doi.org/10.26502/aimr.0202","url":null,"abstract":"<p><p>Glucocorticoids are the cornerstone of asthma therapy due to their potent anti-inflammatory action. However, a subset of severe asthmatics do not respond to the standard glucocorticoid treatment. Such phenomenon is referred to as glucocorticoid insensitivity (GCI). From a clinical point of view, GCI is characterized by the reduced therapeutic response with improvement of less than 10-15% in lung function parameters, such as FEV1, upon the administration of an adequate glucocorticoid dose. The mechanisms underlying GCI involve disrupted glucocorticoid receptor (GR) signaling, overexpression of the dominant-negative GRβ isoform, increased activity of pro-inflammatory transcription factors such as NF-κB and AP-1, and abnormal GR phosphorylation by kinases such as p38 MAPK. These altered molecular pathways undermine the anti-inflammatory effects of glucocorticoids on immune and structural airway cells, thus maintaining the chronicity of airway inflammation and remodeling. GCI can be of innate genetic origin, as in the case of GR mutations, or acquired through environmental exposures, including viral infections, smoking, and long-term exposure to pollutants in the environment. GCI represents a big challenge in the management of asthma, since a large proportion of cases do not achieve an adequate level of control with the standard treatment options. Recent advances in the understanding of the molecular mechanisms underlying GCI have enabled the development of novel therapeutic strategies, including biologic therapies targeting interleukin-5 and IL-13, Janus kinase inhibitors, and small-molecule drugs aimed at restoring GR function. This article presents a critical discussion on the current state of knowledge regarding the glucocorticoid resistance mechanisms in asthma, identifying the clinical effects of new therapeutic strategies, with special emphasis on the need for personalized treatment regimens to improve outcomes in glucocorticoid insensitivity.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"8 2","pages":"107-120"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Assessment of Intracellular Effectors and Cellular Response in RAGE Activation.","authors":"Vinitha Deepu, Vikrant Rai, Devendra K Agrawal","doi":"10.26502/aimr.0168","DOIUrl":"10.26502/aimr.0168","url":null,"abstract":"<p><p>The review delves into the methods for the quantitative assessment of intracellular effectors and cellular response of Receptor for Advanced Glycation End products (RAGE), a vital transmembrane receptor involved in a range of physiological and pathological processes. RAGE bind to Advanced Glycation End products (AGEs) and other ligands, which in turn activate diverse downstream signaling pathways that impact cellular responses such as inflammation, oxidative stress, and immune reactions. The review article discusses the intracellular signaling pathways activated by RAGE followed by differential activation of RAGE signaling across various diseases. This will ultimately guide researchers in developing targeted and effective interventions for diseases associated with RAGE activation. Further, we have discussed how PCR, western blotting, and microscopic examination of various molecules involved in downstream signaling can be leveraged to monitor, diagnose, and explore diseases involving proteins with unique post-translational modifications. This review article underscores the pressing need for advancements in molecular approaches for disease detection and management involving RAGE.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"7 2","pages":"80-103"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11113086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethnic and Racial Disparities in Clinical Manifestations of Atopic Dermatitis.","authors":"Fihr Chaudhary, Devendra K Agrawal","doi":"10.26502/aimr.0170","DOIUrl":"https://doi.org/10.26502/aimr.0170","url":null,"abstract":"<p><p>Atopic dermatitis is a heterogenous inflammatory skin illness that may last for long time and affect people of different racial and ethnic backgrounds. The condition primarily appears in infants and young children. There are people living with atopic dermatitis in every country and every ethnic group, although the frequency of the disease varies greatly. Due to the varied clinical presentations that atopic dermatitis can have, it can be challenging to characterize and diagnose the disease, particularly in adults. Nevertheless, there exists a dearth of information pertaining to the various presentations of atopic dermatitis among individuals from diverse racial and cultural groups. This critical review article offers a succinct and comprehensive overview of the current findings on the epidemiology of atopic dermatitis with regards to ethnic and racial disparities. The findings hold potential significance in advancing the development of targeted treatments for personalized medicine approaches and enhancing the quality of life for patients with atopy.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"7 2","pages":"114-133"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"African Americans Possessed High Prevalence of Comorbidities and Frequent Abdominal Symptoms, and Comprised A Disproportionate Share of Covid-19 Mortality among 9,873 Us- Hospitalized Patients Early in the Pandemic.","authors":"Hassan Ashktorab, Antonio Pizuorno, Lakshmi Gayathri Chirumamilla, Folake Adeleye, Maryam Mehdipour Dalivand, Zaki A Sherif, Gholamreza Oskrochi, Suryanarayana Reddy Challa, Boubini Jones-Wonni, Sheldon Rankine, Chiamaka Ekwunazu, Abigail Banson, Rachel Kim, Chandler Gilliard, Elizabeth Ekpe, Nader Shayegh, Constance Nyaunu, Chidi Martins, Ashley Slack, Princess Okwesili, Malachi Abebe, Yashvardhan Batta, Do Ly, Ogwo Valarie, Tori Smith, Kyra Watson, Oluwapelumi Kolawole, Sarine Tahmazian, Sofiat Atoba, Myra Khushbakht, Gregory Riley, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph Miller, Fatimah Jackson, John M Carethers, Vinod Rustgi, Hassan Brim","doi":"10.26502/aimr.0163","DOIUrl":"https://doi.org/10.26502/aimr.0163","url":null,"abstract":"<p><strong>Background and aim: </strong>Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities.</p><p><strong>Design setting and participants: </strong>We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients.</p><p><strong>Results: </strong>Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality.</p><p><strong>Conclusion: </strong>These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"7 1","pages":"27-41"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Targeting p27^kip1 in Plaque Vulnerability.","authors":"Jerry Trinh, Jennifer Shin, Vikrant Rai, Devendra K Agrawal","doi":"10.26502/aimr.0167","DOIUrl":"10.26502/aimr.0167","url":null,"abstract":"<p><p>Atherosclerosis, a critical contributor to coronary artery diseases, involves the accumulation of cholesterol, fibrin, and lipids within arterial walls, inciting inflammatory reactions culminating in plaque formation. This multifaceted interplay encompasses excessive fibrosis, fatty plaque development, vascular smooth muscle cell (VSMC) proliferation, and leukocyte migration in response to inflammatory pathways. While stable plaques demonstrate resilience against complications, vulnerable ones, with lipid-rich cores, necrosis, and thin fibrous caps, lead to thrombosis, myocardial infarction, stroke, and acute cerebrovascular accidents. The nuanced phenotypes of VSMCs, modulated by gene regulation and environmental cues, remain pivotal. Essential markers like alpha-SMA, myosin heavy chain, and calponin regulate VSMC migration and contraction, exhibiting diminished expression during VSMC de-differentiation and proliferation. p27^kip, a CDK inhibitor, shows promise in regulating VSMC proliferation and appears associated with TNF-α-induced pathways impacting unstable plaques. Oncostatin M (OSM), an IL-6 family cytokine, correlates with MMP upregulation and foam cell formation, influencing plaque development. Efforts targeting mammalian target of rapamycin (mTOR) inhibition, notably using rapamycin and its analogs, demonstrate potential but pose challenges due to associated adverse effects. Exploration of the impact of p27^kip impact on plaque macrophages presents promising avenues, yet its complete therapeutic potential remains untapped. Similarly, while OSM has exhibited potential in inducing cell cycle arrest via p27^kip, direct links necessitate further investigation. This critical review discusses the role of mTOR, p27^kip, and OSM in VSMC proliferation and differentiation followed by the therapeutic potential of targeting these mediators in atherosclerosis to attenuate plaque vulnerability.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"7 2","pages":"73-79"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}