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Experimental & Molecular Medicine Mar 2024Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections,... (Review)
Review
Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Macrophages
PubMed: 38448692
DOI: 10.1038/s12276-024-01182-6 -
Heliyon Mar 2024Diabetes mellitus (DM) is one of the fastest-growing diseases worldwide; however, its pathogenesis remains unclear. Complications seriously affect the quality of life of... (Review)
Review
CONTEXT
Diabetes mellitus (DM) is one of the fastest-growing diseases worldwide; however, its pathogenesis remains unclear. Complications seriously affect the quality of life of patients in the later stages of diabetes, ultimately leading to suffering. Natural small molecules are an important source of antidiabetic agents.
OBJECTIVE
Astragaloside IV (AS-IV) is an active ingredient of Astragalus mongholicus (Fisch.) Bunge. We reviewed the efficacy and mechanism of action of AS-IV in animal and cellular models of diabetes and the mechanism of action of AS-IV on diabetic complications in animal and cellular models. We also summarized the safety of AS-IV and provided ideas and rationales for its future clinical application.
METHODS
Articles on the intervention in DM and its complications using AS-IV, such as those published in SCIENCE, PubMed, Springer, ACS, SCOPUS, and CNKI from the establishment of the database to February 2022, were reviewed. The following points were systematically summarized: dose/concentration, route of administration, potential mechanisms, and efficacy of AS-IV in animal models of DM and its complications.
RESULTS
AS-IV has shown therapeutic effects in animal models of DM, such as alleviating gestational diabetes, delaying diabetic nephropathy, preventing myocardial cell apoptosis, and inhibiting vascular endothelial dysfunction; however, the potential effects of AS-IV on DM should be investigated.
CONCLUSION
AS-IV is a potential drug for the treatment of diabetes and its complications, including diabetic vascular disease, cardiomyopathy, retinopathy, peripheral neuropathy, and nephropathy. In addition, preclinical toxicity studies indicate that it appears to be safe, but the safe human dose limit is yet to be determined, and formal assessments of adverse drug reactions among humans need to be further investigated. However, additional formulations or structural modifications are required to improve the pharmacokinetic parameters and facilitate the clinical use of AS-IV.
PubMed: 38439832
DOI: 10.1016/j.heliyon.2024.e26863 -
Journal of Oleo Science 2024Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to...
Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to one molecule of glycerol. Drug delivery system (DDS) is defined as a formulation to distribute drugs into the human body. The unique properties of MCTs have garnered interest in using them as excipients in DDS. Even though there are many significant effects attributed to the use of MCTs, especially in modulating the rate of drug delivery in various DDS, they are all limited and intermittent. This warrants a detailed summary of the previous studies on the use of MCTs in various DDS. Therefore, this review focuses on presenting a systematic review of previous studies on the use of MCTs in the last six years and explores the types and effects of MCTs on DDS that employ various types of delivery routes. A systematic search through PubMed, Science Direct and Scopus was performed. Keywords like "medium-chain triglycerides", "medium-chain fatty acids", "medium-chain triglycerides and their fractions", "medium-chain fatty acids and their fractions", "MCTs", "MCFA", "in drug delivery", "in drug delivery system" and their combinations were used. The synonyms of the words were also used to extend the search. A total of 17 articles that met the inclusion criteria were identified. Findings from this review have identified the several MCTs and their fractions used in DDS that employed the oral/enteral, topical, transdermal, parenteral, and pulmonary routes of drug delivery. The review also highlights that the usage of MCTs in DDS results in a better transportation of drugs into the human body.
Topics: Humans; Drug Delivery Systems; Carbon; Excipients; Fatty Acids; Triglycerides
PubMed: 38432994
DOI: 10.5650/jos.ess23204 -
Drug Discoveries & Therapeutics Mar 2024Endometriosis (EM), also known as Zhengjia in traditional Chinese medicine, is a common disease that significantly impacts women's health. An integrated treatment...
Endometriosis (EM), also known as Zhengjia in traditional Chinese medicine, is a common disease that significantly impacts women's health. An integrated treatment approach combining traditional Chinese medicine (TCM) and western medicine has demonstrated significant clinical efficacy in the management of this condition. Specifically, it has been effective in addressing blood circulation and other diseases. MicroRNAs (miRNAs), which are molecules important in gene regulation, have been implicated in various physiologic and pathologic processes. In this review, we systematically summarized the potential mechanisms underlying the integrated EM treatment, with a focus on the role of microRNAs (miRNAs). Current research suggests that integrated TCM and western medicine treatment may exert their therapeutic effects on EM by influencing the expression of miRNAs. Through miRNA modulation, such a treatment approach may inhibit the growth of ectopic lesions and alleviate clinical symptoms. This review will shed light on the specific miRNAs that have been implicated in the integrated treatment of EM, as well as their potential mechanisms of action. By consolidating the existing evidence, we aim to provide clinicians and researchers with a clearer understanding of the therapeutic benefits of the integrated approach and potentially identify new avenues for improving clinical treatment outcomes. Ultimately, this review will contribute to the growing body of knowledge in this field, providing a basis for further research and the development of more targeted and efficient treatment strategies for EM.
Topics: Humans; Female; Medicine, Chinese Traditional; MicroRNAs; Endometriosis; Treatment Outcome; Drugs, Chinese Herbal
PubMed: 38417896
DOI: 10.5582/ddt.2024.01004 -
Atherosclerosis Plus Mar 2024Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable... (Review)
Review
Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.
Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.
PubMed: 38379882
DOI: 10.1016/j.athplu.2024.01.003 -
Heliyon Feb 2024Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both...
BACKGROUND
Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both their clinical use and the development of novel regimens. However, the identification and management of their associated toxicities poses challenges for clinicians and researchers.
METHODS
A systematic review and meta-analysis of randomized controlled trials (RCTs) published from January 1, 2000, to October 15, 2022, and in the databases. A random-effects model with logit transformation was applied to the analysis heterogeneity between studies was evaluated using the I statistic with incidence and 95 % confidence interval (CI) for any adverse events (AEs), and serious AEs (SAEs).
RESULTS
In Crohn's disease (CD), the total AE incidence was 67.0 % (95 % CI, 66.2%-67.8 %; I = 97.2 %) for any AEs and 7.3 % (6.9-7.7; 97.2) for serious AEs. In ulcerative colitis (UC), the overall incidence of any and serious AEs was 63.6 % (63.0-64.3; 98.1) and 5.7 % (5.4-6.0; 88.9), respectively. The most common AEs were infections (21.5 [20.3-22.8], 32.6 [31.0-34.2], 25.9 [24.5-27.2], and 13.7 [10.7-16.7]) in CD patients that were treated with TNF antagonists, anti-integrins, anti-IL agents, and JAK inhibitors, respectively, and in UC patients also were infections (22.8 [21.7-24.0], 27.4 [25.9-28.9], and 18.4 [16.7-20.2]), respectively, as well as increases in lactic dehydrogenase levels (23.1 [20.8-25.4]) with JAK inhibitors.
CONCLUSION
This study offers a comprehensive summary of toxic side effects of IBD treatments and a useful reference for both patients and clinicians.
PubMed: 38370239
DOI: 10.1016/j.heliyon.2024.e25357 -
Plastic and Reconstructive Surgery.... Feb 2024Lymphatic dyes are commonly used to map the drainage path from tumor to lymphatics, which are biopsied to determine if spread has occurred. A blue dye in combination...
BACKGROUND
Lymphatic dyes are commonly used to map the drainage path from tumor to lymphatics, which are biopsied to determine if spread has occurred. A blue dye in combination with technetium-99 is considered the gold standard for mapping, although many other dyes and dye combinations are used. Not all of these substances have the same detection efficacy.
METHODS
A systematic review of PubMed, SCOPUS, Web of Science, and Medline was performed. The predefined search terms were (indocyanine green OR isosulfan blue OR lymphazurin OR patent blue OR methylene blue OR fluorescein OR technetium-99) AND combination AND dye AND (sentinel lymph node biopsy OR lymphedema OR lymphatics OR lymph OR microsurgery OR cancer OR tumor OR melanoma OR carcinoma OR sarcoma).
RESULTS
The initial search returned 4267 articles. From these studies, 37 were selected as candidates that met inclusion criteria. After a full-text review, 34 studies were selected for inclusion. Eighty-nine methods of sentinel lymph node (SLN) detection were trialed using 22 unique dyes, dye combinations, or other tracers. In total, 12,157 SLNs of 12,801 SLNs were identified. Dye accuracy ranged from 100% to 69.8% detection. Five dye combinations had 100% accuracy. Dye combinations were more accurate than single dyes.
CONCLUSIONS
Combining lymphatic dyes improves SLN detection results. Replacing technetium-99 with ICG may allow for increased access to SLN procedures with comparable results. The ideal SLN tracer is a low-cost molecule with a high affinity for lymphatic vessels due to size and chemical composition, visualization without specialized equipment, and no adverse effects.
PubMed: 38333031
DOI: 10.1097/GOX.0000000000005598 -
EFORT Open Reviews Feb 2024The aim of this study was to conduct a systematic literature review analyzing the results of in vivo rat femoral defect models using biomaterials for improving the...
PURPOSE
The aim of this study was to conduct a systematic literature review analyzing the results of in vivo rat femoral defect models using biomaterials for improving the induced membrane technique (IMT).
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed, Embase, and Web of Science databases were searched. Inclusion criteria were studies reporting results of the IMT in in vivo rat femoral critical-sized defect models using a biomaterial possibly combined with molecules. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments guidelines.
RESULTS
Twenty studies met the inclusion criteria. Femoral stabilization with plate and screws was the most frequent. Histologic, biomechanical, and/or radiologic analyses were performed. In two-stage strategies, the PMMA spacer could be associated with bioactive molecules to enhance IM growth factor expression and improve bone formation. Modulating the roughness of spacers could increase IM thickness and accelerate its formation. In one-stage strategies, human tissue-derived membranes combined with bone grafting achieved bone formation comparable to a standard IMT. All calcium phosphate grafts seemed to require a functionalization with growth factors or bone marrow mononuclear cells to improve outcomes compared with non-functionalized grafts.
CONCLUSION
This systematic review described the main parameters of the in vivo rat femoral defect models using biomaterials to improve the induced membrane technique. Although the studies included had several methodological limitations that may limit the scope of these conclusions, one- and two-stage strategies reported promising results with biomaterials to improve the IMT.
PubMed: 38320402
DOI: 10.1530/EOR-23-0055 -
JVS-vascular Science 2024Peripheral artery disease (PAD) impacts more than 200 million people worldwide. The understanding of the genetics of the disease and its clinical implications continue... (Review)
Review
BACKGROUND
Peripheral artery disease (PAD) impacts more than 200 million people worldwide. The understanding of the genetics of the disease and its clinical implications continue to evolve. This systematic review provides a comprehensive summary of all DNA variants that have been studied in association with the diagnosis and progression of PAD, with a meta-analysis of the ones replicated in the literature.
METHODS
A systematic review of all studies examining DNA variants associated with the diagnosis and progression of PAD was performed. Candidate gene and genome-wide association studies (GWAS) were included. A meta-analysis of 13 variants derived from earlier smaller candidate gene studies of the diagnosis of PAD was performed. The literature on the progression of PAD was limited, and a meta-analysis was not feasible because of the heterogeneity in the criteria used to characterize it.
RESULTS
A total of 231 DNA variants in 112 papers were studied for the association with the diagnosis of PAD. There were significant variations in the definition of PAD and the selection of controls in the various studies. GWAS have established 19 variants associated with the diagnosis of PAD that were replicated in several large patient cohorts. Only variants in intercellular adhesion molecule-1 (rs5498), IL-6 (rs1800795), and hepatic lipase (rs2070895) showed significant association with the diagnosis of PAD. However, these variants were not noted in the published GWAS.
CONCLUSIONS
Genetic research in the diagnosis of PAD has significant heterogeneity, but recent GWAS have demonstrated variants consistently associated with the disease. More research focusing on the progression of PAD is needed to identify patients at risk of adverse events and develop strategies that would improve their outcomes.
PubMed: 38314202
DOI: 10.1016/j.jvssci.2023.100133 -
Clinical Medicine & Research Dec 2023Lichen planus (LP) is a chronic autoimmune disease of skin and mucous membranes. World Health Organization has announced oral lichen planus (OLP) as a premalignant... (Review)
Review
Lichen planus (LP) is a chronic autoimmune disease of skin and mucous membranes. World Health Organization has announced oral lichen planus (OLP) as a premalignant lesion. The exact etiology of OLP remains unknown; however, different mechanisms may be involved in its immunopathogenesis. The upregulation of cytokines, chemokines, and adhesion molecules is consistent with a persistent and erratic immunological response to OLP-mediated antigens generated by oral keratinocytes and innate immune cells. These molecules attract T cells, and mast cells to the disease site and regulate complex interactions among cells that lead to death of keratinocytes, degradation of basement membrane, and chronicity of the disease. It is believed that CD8+ and CD4+ T helper 1 (Th1) cells are the main lymphocytes involved in this process, although recent evidence suggests implication of other T helper subgroups, such as Th23, Th17, and regulatory T cells (Tregs), proposing a more complex cellular immunity process to be involved in its pathogenesis. The emphasis of this research review is on the function of IL-17 in the pathophysiology of OLP and how current discoveries may point to future treatment strategies. This research protocol will follow Preferred Reporting Items for Systematic Reviews (PRISMA 2020) checklist. An electronic search was conducted in PubMed, Scopus, Google Scholar, Embase, and Cochrane databases for articles published from 1960 to June 2022. Based on the eligibility criteria, 21 articles were enrolled. In comparison to healthy controls, the findings of this review demonstrated greater expression of IL-17 and Th-17 in the blood, saliva, and tissues of OLP and LP patients. Additionally, there was a strong link between the relative levels of IL-17 and IL-23 expression. Treatment with monoclonal antibodies against Th-17/Tc-17, IL-12/IL-23, and IL-23 would result in significant long-term improvement of LP symptoms.
Topics: Humans; Lichen Planus, Oral; Interleukin-17; Cytokines; Lichen Planus; Interleukin-23
PubMed: 38296640
DOI: 10.3121/cmr.2023.1822