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Aging and Disease Feb 2022Aging is a prominent risk factor for cardiovascular diseases, which is the leading cause of death around the world. Recently, cellular senescence has received potential... (Review)
Review
Aging is a prominent risk factor for cardiovascular diseases, which is the leading cause of death around the world. Recently, cellular senescence has received potential attention as a promising target in preventing cardiovascular diseases, including acute myocardial infarction, atherosclerosis, cardiac aging, pressure overload-induced hypertrophy, heart regeneration, hypertension, and abdominal aortic aneurysm. Here, we discuss the mechanisms underlying cellular senescence and describe the involvement of senescent cardiovascular cells (including cardiomyocytes, endothelial cells, vascular smooth muscle cells, fibroblasts/myofibroblasts and T cells) in age-related cardiovascular diseases. Then, we highlight the targets (SIRT1 and mTOR) that regulating cellular senescence in cardiovascular disorders. Furthermore, we review the evidence that senescent cells can exert both beneficial and detrimental implications in cardiovascular diseases on a context-dependent manner. Finally, we summarize the emerging pro-senescent or anti-senescent interventions and discuss their therapeutic potential in preventing cardiovascular diseases.
PubMed: 35111365
DOI: 10.14336/AD.2021.0927 -
Pharmacology & Therapeutics Jan 2024The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not... (Review)
Review
The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.
Topics: Animals; Connective Tissue Growth Factor; Fibrosis; Fibroblasts; Transforming Growth Factor beta; Idiopathic Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung
PubMed: 38103794
DOI: 10.1016/j.pharmthera.2023.108578 -
Journal of Clinical Medicine Nov 2023Low-grade myofibroblastic sarcoma (LGMS) is a rare tumor entity which occurs in the subcutaneous and deep soft tissues; it is less common in the bone with a predilection... (Review)
Review
INTRODUCTION
Low-grade myofibroblastic sarcoma (LGMS) is a rare tumor entity which occurs in the subcutaneous and deep soft tissues; it is less common in the bone with a predilection for the extremities and the head and neck region. As confirming the diagnosis is difficult and treatment strategies are not standardized, we aimed to identify patient and tumor characteristics, and to summarize treatment strategies and their clinical outcomes to guide surgeons.
METHODS
Included were full articles reporting patients with histology of LGMS in the extremities, excluding tumors of the trunk. All patients underwent surgery but with different extend, from marginal to wide resection. Included studies should inform about local recurrence, metastasis, or evidence of disease, depending on the surgical treatment. We conducted a structured search using MEDLINE (via PubMed), Web of Science, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies on low-grade myofibroblastic sarcoma of the extremities. Study designs like randomized controlled trials, systematic reviews, prospective trials, retrospective studies, and case reports were included. Prospective studies and comparative studies were not available at all. Therefore, meta-analysis was not possible and statistical analysis was purely descriptive.
RESULTS
Of the 789 studies identified from our initial search, 17 studies including 59 cases reported LGMS of the extremities with the surgical treatment and clinical outcome and were therefore analyzed. In addition, we present the rare case and surgical management of a 28-year-old male patient with residual LGMS of the thumb after an initial incomplete resection. The current literature suggests that a wide excision with R0 margins should be considered the standard treatment for LGMS. In cases where surgery leads to significant functional impairment, individual options like free tissue transfer from a donor site have to be considered. Therefore, we also present an illustrative case. For all selected case series and case reports, a high risk of confounding, selection bias, information bias, and reporting bias must be anticipated. Nevertheless, this systematic review provides a comprehensive overview on surgical treatment and clinical outcomes in LGMS surgery of the extremities.
PubMed: 38002641
DOI: 10.3390/jcm12227027 -
BioMed Research International 2022The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of... (Review)
Review
BACKGROUND
The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19.
METHODS
A systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. . After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. . We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.
Topics: COVID-19; Exosomes; Humans; Mesenchymal Stem Cells; Prospective Studies; Pulmonary Fibrosis
PubMed: 35782071
DOI: 10.1155/2022/9346939 -
Asian Pacific Journal of Cancer... May 2024To systematically review the existing scientific literature in providing a comprehensive, quantitative analysis on the prognostic ability of Cancer Associated... (Meta-Analysis)
Meta-Analysis
AIM
To systematically review the existing scientific literature in providing a comprehensive, quantitative analysis on the prognostic ability of Cancer Associated Fibroblasts (CAFs) in Oral Squamous Cell Carcinoma (OSCC) a novel meta-analysis.
METHODS
Review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and registered in PROSPERO - CRD CRD42023467899. Electronic databases were searched for studies having data on effect of CAFs on overall survival rate and disease prognosis in patients with OSCC, oral epithelial dysplasia (OED) compared to normal healthy controls. Quality assessment of included was evaluated through Newcastle Ottawa scale (NOS) for included studies through its domains. The hazard ratio (HR) and risk ratio (RR) was used as summary statistic measure with random effect model and p value <0.05 as statistically significant.
RESULTS
Twenty studies fulfilled the eligibility criteria and were included in qualitative synthesis and eighteen studies for meta -analysis. Included studies had moderate to low risk of bias. It was observed through the pooled estimate that overall survival rate - (HR) =2.30 (1.71 - 3.10) was lesser in group with high CAFs compared to low CAFs while pooled estimate through RR =1.53 (0.73 - 3.19) and RR = 5.72 (2.40 - 13.59) signified that overall survival rate was lower n OSCC patients with high CAF compared to patients with OED and healthy controls. Publication bias through the funnel plot showed asymmetric distribution with presence of systematic heterogeneity indicating presence of publication bias.
CONCLUSION
Abundance of CAFs in tumor stroma of OSCC patients is associated with overall poor survival rate and poor disease prognosis. CAFs acts as a good prognostic and therapeutic marker in disease progression and advancements and should be assessed early to reduce patient's mortality and morbidity.
Topics: Humans; Mouth Neoplasms; Prognosis; Myofibroblasts; Carcinoma, Squamous Cell; Survival Rate; Biomarkers, Tumor
PubMed: 38809619
DOI: 10.31557/APJCP.2024.25.5.1477 -
Journal of Oral Pathology & Medicine :... May 2024Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF)... (Review)
Review
BACKGROUND
Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features.
METHODS
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report.
RESULTS
A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases.
CONCLUSION
MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.
PubMed: 38711183
DOI: 10.1111/jop.13537 -
Irish Journal of Medical Science Apr 2023Desmoid tumours are benign fibromatous tumours arising from dysregulated myofibroblast proliferation within musculoaponeurotic structures. They can occur sporadically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Desmoid tumours are benign fibromatous tumours arising from dysregulated myofibroblast proliferation within musculoaponeurotic structures. They can occur sporadically but more commonly are associated with genetic syndromes such as familial adenomatous polyposis (Sakorafas et al. in Surg Oncol 16(2):131-142, 2007) (FAP). Mutations in either the Wnt, β-catenin or APC genes are 'key' triggers for the development of these tumours (Howard and Pollock in Oncol Ther 4(1):57-72, 2016). Classically, these tumours do not metastasise; however, they are associated with significant morbidity and mortality due to their infiltrative pattern and/or local invasion. Historically, surgical resection was the cornerstone of treatment. There remains paucity of data regarding outcomes following the surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity.
OBJECTIVES
The aim of this review was to assess the current evidence for surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity.
METHODS
A systematic search of articles in PubMed, EMBASE and The Cochrane Library databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the period from January 2000 to November 2020.
RESULTS
Twenty-three studies were included, of which, 749 patients had surgical resection (696 for primary and 53 for recurrent desmoids), 243 patients (18.8%) were medically managed and 353 patients (27.3%) underwent surveillance. Median follow-up was 51.4 months (range 1-372). Six-hundred and ninety-six of the 749 resections (92.9%) underwent primary desmoid resection, with the remaining 53 (7.1%) undergoing resection for recurrence. One-hundred and two surgically managed patients (19%) developed a (re)recurrence, with mesenteric involvement the commonest site for recurrence (55%). When comparing recurrence post-surgery to progression following medical therapy, there was a trend towards better outcomes with surgery, with 25% of surgical patients having a recurrence versus 50.5% having progression with medical therapy [OR 0.40 (95% CI 0.06-2.70), p = 0.35]. Major morbidity following surgery was 4.4% (n = 33) with 2% (n = 14) mortality within 30 days of resection.
CONCLUSION
The management of desmoids has considerable heterogeneity. Surgical resection for abdominal desmoids remains a valid treatment option in highly selective cases where negative margins can be obtained, with low major morbidity and/or mortality.
Topics: Humans; Fibromatosis, Aggressive; Fibromatosis, Abdominal; Adenomatous Polyposis Coli; Mutation; Colectomy
PubMed: 35445926
DOI: 10.1007/s11845-022-03008-8 -
JBJS Reviews Jan 2021Frozen shoulder is a common, poorly understood condition affecting the shoulder joint, with poor long-term outcomes in some in relation to pain and mobility....
BACKGROUND
Frozen shoulder is a common, poorly understood condition affecting the shoulder joint, with poor long-term outcomes in some in relation to pain and mobility. Understanding the pathophysiology of frozen shoulder at a cellular level and a molecular level may help in the development of novel treatments. The aim of this study was to perform a systematic review of studies examining the cellular, molecular, and metabolic findings in frozen shoulder.
METHODS
A literature search was conducted using Embase, CINAHL (Cumulative Index of Nursing and Allied Health Literature), and PubMed using relevant terms. Studies were included if they assessed cellular, molecular, or metabolic alterations in tissue or blood samples of patients with frozen shoulder.
RESULTS
Of 4,794 studies identified, 25 were included for analysis. Histological findings included nonspecific chronic inflammation and the proliferation of fibroblasts, adipocytes, and blood vessels. Molecular studies showed increased pro-inflammatory mediators, reduced matrix metalloproteinases (MMPs), and increased activity of factors promoting fibroblast activation and nerve growth. Metabolic alterations included an increase in blood lipids.
CONCLUSIONS
Frozen shoulder is thought to occur after a primary insult to the shoulder triggers a complex cascade and upregulation of growth factors and cytokines with an increased turnover of the extracellular matrix, activation of myofibroblasts with deposition of collagen, and reduced matrix degradation. The presence of a background pro-inflammatory state (e.g., patients with diabetes or hyperlipidemia) may exacerbate these abnormalities. Further work assessing patients in early stages of the disease and comparing the inflammatory or fibrogenic characteristics of the shoulder capsule with those of the other joints may help to determine the initiating factors and to explain the predisposition of the shoulder to stiffness.
CLINICAL RELEVANCE
Our findings may form the basis for identifying new targets for the clinical management of frozen shoulder.
Topics: Bursitis; Humans; Inflammation; Matrix Metalloproteinases; Shoulder; Shoulder Joint
PubMed: 33512972
DOI: 10.2106/JBJS.RVW.19.00153 -
Advances in Medical Sciences Mar 2022Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential.... (Review)
Review
BACKGROUND
Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential. These tumors contain proliferating neoplastic, fibroblastic and myofibroblastic cells, and are also characterized by chronic inflammatory infiltration by lymphocytes, plasma cells, eosinophils, and histiocytes. They belong to the group of inflammatory spindle cell lesions. Some reactive lesions, such as inflammatory pseudotumors, may appear to be IMTs, which makes their differential diagnosis extremely difficult. The aim of this article is to compile the recent information on IMTs to aid in their diagnosis and treatment.
METHODS
We reviewed articles published between 2017 and 2021, which were selected from online medical databases. In addition, some earlier articles and latest scientific monographies were analyzed.
RESULTS
The terminology used for inflammatory spindle cell lesions seems to be confusing. The terms "inflammatory myofibroblastic tumors" and "inflammatory pseudotumors" are interchangeably used by many scientists. However, a detailed analysis of the development of terminology suggests that the term "inflammatory myofibroblastic tumors" should be used to refer to a neoplastic lesion.
CONCLUSIONS
IMTs are rare neoplasms, which have not been investigated in detail due to the difficulty in collecting a large number of cases. Thus, our knowledge about this disease remains unsatisfactory. Recently developed techniques such as next-generation sequencing and computer-aided histopathological diagnosis may be useful in understanding the etiopathology of IMTs, which will help in the selection of the most appropriate therapy for patients.
Topics: Diagnosis, Differential; Granuloma, Plasma Cell; Humans; Inflammation; Myofibroblasts
PubMed: 35219201
DOI: 10.1016/j.advms.2022.02.002 -
Investigative Ophthalmology & Visual... Apr 2021Interleukin (IL)-1α/IL-1β and transforming growth factor (TGF)β1/TGFβ2 have both been promoted as "master regulators" of the corneal wound healing response due to...
PURPOSE
Interleukin (IL)-1α/IL-1β and transforming growth factor (TGF)β1/TGFβ2 have both been promoted as "master regulators" of the corneal wound healing response due to the large number of processes each regulates after injury or infection. The purpose of this review is to highlight the interactions between these systems in regulating corneal wound healing.
METHODS
We conducted a systematic review of the literature.
RESULTS
Both regulator pairs bind to receptors expressed on keratocytes, corneal fibroblasts, and myofibroblasts, as well as bone marrow-derived cells that include fibrocytes. IL-1α and IL-1β modulate healing functions, such as keratocyte apoptosis, chemokine production by corneal fibroblasts, hepatocyte growth factor (HGF), and keratinocyte growth factor (KGF) production by keratocytes and corneal fibroblasts, expression of metalloproteinases and collagenases by corneal fibroblasts, and myofibroblast apoptosis. TGFβ1 and TGFβ2 stimulate the development of myofibroblasts from keratocyte and fibrocyte progenitor cells, and adequate stromal levels are requisite for the persistence of myofibroblasts. Conversely, TGFβ3, although it functions via the same TGF beta I and II receptors, may, at least in some circumstances, play a more antifibrotic role-although it also upregulates the expression of many profibrotic genes.
CONCLUSIONS
The overall effects of these two growth factor-cytokine-receptor systems in controlling the corneal wound healing response must be coordinated during the wound healing response to injury or infection. The activities of both systems must be downregulated in coordinated fashion to terminate the response to injury and eliminate fibrosis.
TRANSLATIONAL RELEVANCE
A better standing of the IL-1 and TGFβ systems will likely lead to better approaches to control the excessive healing response to infections and injuries leading to scarring corneal fibrosis.
Topics: Biomarkers; Cornea; Corneal Injuries; Humans; Transforming Growth Factor beta; Wound Healing
PubMed: 33825855
DOI: 10.1167/iovs.62.4.8