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International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
The Japanese Dental Science Review Dec 2024Oral cancer became a very common condition. WHO estimates that there are 4 cases of lip and oral cavity cancer for every 100,000 people worldwide. The early diagnosis of... (Review)
Review
Salivary biomarkers for early detection of oral squamous cell carcinoma (OSCC) and head/neck squamous cell carcinoma (HNSCC): A systematic review and network meta-analysis.
Oral cancer became a very common condition. WHO estimates that there are 4 cases of lip and oral cavity cancer for every 100,000 people worldwide. The early diagnosis of cancers is currently a top focus in the health sector. Recent systematic reviews and meta-analyses have identified promising biomarkers for early detection in several original research investigations. However, it is still unclear the quality of these evidence and which biomarker performs the best in terms of early detection. Therefore, the objective was, to map the methodological and reporting quality of available oral squamous cell carcinoma (OSCC) or head/neck squamous cell carcinoma (HNSCC) systematic reviews and meta-analysis. Secondly, to evaluate diagnostic accuracy of salivary biomarkers for common craniofacial cancers and to compare the diagnostic value of different salivary biomarkers. PubMed, Scopus, Web of Science, Embase and Cochrane Library electronic databases were used to map the methodological and reporting quality of the systematic reviews and meta-analysis conducted on the HNSCC, OSCC using the AMSTAR-2 checklist. The inclusion criteria were systematic reviews and meta-analysis published in the topic of HNSCC and OSCC biomarkers. Exclusion criteria were no animal studies; original primary studies, due to limitation of competency in other languages articles with language other than English were excluded. The sensitivity and specificity were calculated for salivary biomarkers and ranked according to network meta-analysis principles. A total of N = 5893 patients were included from four meta-analysis studies. All together, these included n = 37 primary studies. n = 94 biomarkers were pooled from these four meta-analyses and categorised into the stages at which they were detected (I-IV). In OSCC, Chemerin and MMP-9 displayed the highest sensitivity, registering 0.94 (95% CI 0.78, 1.00) and a balanced accuracy of 0.93. Phytosphingosine closely followed, with a sensitivity of 0.91 (95% CI 0.68, 0.99) and a balanced accuracy of 0.87. For HNSCC, the top three biomarkers are Actin, IL-1β Singleplex, and IL-8 ELISA. Actin leads with a sensitivity of 0.91 (95% CI 0.68-0.99), a specificity of 0.67, and an overall accuracy of 0.79. Subsequently, IL-1β Singleplex exhibits a sensitivity of 0.62 (95% CI 0.30-0.88), a specificity of 0.89, and an accuracy of 0.75, followed by IL-8 ELISA with a sensitivity of 0.81 (95% CI 0.54-0.97), a specificity of 0.59, and an accuracy of 0.70. In conclusion, there was highest sensitivity for MMP-9 and chemerin salivary biomarkers. There is need of further more studies to identify biomarkers for HNSCC and OSCC.
PubMed: 38204964
DOI: 10.1016/j.jdsr.2023.10.003 -
Computational and Structural... 2023Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological... (Review)
Review
Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological systems fulfill different functions and often form dynamic networks that respond to perturbations. Therefore, characterizing the properties of filamentous structures and the networks they form is important to gain better understanding of systems level functions and dynamics. Filamentous structures are captured by various imaging technologies, and analysis of the resulting imaging data addresses two problems: (i) identification (tracing) of filamentous structures in a single snapshot and (ii) characterizing the dynamics (., tracking) of filamentous structures over time. Therefore, considerable research efforts have been made in developing automated methods for tracing and tracking of filamentous structures. Here, we provide a systematic review in which we present, categorize, and discuss the state-of-the-art methods for tracing and tracking of filamentous structures in sparse and dense networks. We highlight the mathematical approaches, assumptions, and constraints particular for each method, allowing us to pinpoint outstanding challenges and offer perspectives for future research aimed at gaining better understanding of filamentous structures in biological systems.
PubMed: 36618983
DOI: 10.1016/j.csbj.2022.12.023 -
Journal of Pediatric Gastroenterology... May 2022The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms...
BACKGROUND AND AIMS
The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms of intestinal dysmotility disorders. we aimed to describe the diverse phenotype of this newly reported and rare disease.
METHODS
Report of 4 new patients, and a systematic review of ACTG2-related disorders. we analyzed the population frequency and used in silico gene damaging predictions. Genotype-phenotype correlations were explored.
RESULTS
One hundred three patients (52% girls), from 14 publications, were included. Twenty-eight unique variants were analyzed, all exceedingly rare, and 27 predicted to be highly damaging. The median Combined Annotation Dependent Depletion (CADD) score was 29.2 (Interquartile range 26.3-29.4). Most patients underwent abdominal surgery (66%), about half required intermittent bladder catheterization (48.5%), and more than half were parenteral nutrition (PN)-dependent (53%). One-quarter of the patients died (25.7%), and 6 required transplant (5.8%). Girls had a higher rate of microcolon (P = 0.009), PN dependency (P = 0.003), and death/transplant (P = 0.029) compared with boys, and early disease onset (<2 years of age) was associated with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) features. There was no statistical association between disease characteristics and CADD scores.
CONCLUSIONS
Damaging ACTG2 variants are rare, often associated with MMIHS phenotype, and overall have a wide phenotypic variation. Symptoms usually present in the perinatal period but can also appear at a later age. The course of the disease is marked by frequent need for surgical interventions, PN support, and mortality. Poor outcomes are more common among girls with ACTG2 variants.
Topics: Abnormalities, Multiple; Actins; Colon; Female; Humans; Intestinal Pseudo-Obstruction; Male; Phenotype; Pregnancy; Urinary Bladder
PubMed: 35149643
DOI: 10.1097/MPG.0000000000003400 -
Cancers Feb 2024The study cohort consisted of 83 patients with a mean age of 49.55 (SD 13.72) with a female preponderance (60 patients). Here, 32.14% of patients had primary LTS; the... (Review)
Review
The study cohort consisted of 83 patients with a mean age of 49.55 (SD 13.72) with a female preponderance (60 patients). Here, 32.14% of patients had primary LTS; the remaining were metastases. Clinical presentation included nonspecific back pain (57.83%), weakness (21.69%) and radicular pain (18.07%). History of uterine neoplasia was found in 33.73% of patients. LTS preferentially affected the thoracic spine (51.81%), followed by the lumbar (21.67%) spine. MRI alone was the most common imaging modality (33.33%); in other cases, it was used with CT (22.92%) or X-ray (16.67%); 19.23% of patients had Resection/Fixation, 15.38% had Total en bloc spondylectomy, and 10.26% had Corpectomy. A minority of patients had laminectomy and decompression. Among those with resection, 45.83% had a gross total resection, 29.17% had a subtotal resection, and 16.67% had a near total resection. Immunohistochemistry demonstrated positivity for actin (43.37%), desmin (31.33%), and Ki67 (25.30). At a follow-up of 19.3 months, 61.97% of patients were alive; 26.25% of 80 patients received no additional treatment, 23.75% received combination radiotherapy and chemotherapy, only chemotherapy was given to 20%, and radiotherapy was given to 17.5%. Few (2.5%) had further resection. For an average of 12.50 months, 42.31% had no symptoms, while others had residual (19.23%), other metastasis (15.38%), and pain (7.69%). On follow-up of 29 patients, most (68.97%) had resolved symptoms; 61.97% of the 71 patients followed were alive.
PubMed: 38398139
DOI: 10.3390/cancers16040748 -
Frontiers in Physiology 2022Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca to troponin C relieves this...
Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca to troponin C relieves this inhibition by changing contacts among the regulatory components and ultimately repositioning tropomyosin on the actin filament creating a state that is permissive for contraction. Several lines of evidence suggest that there are three possible positions of tropomyosin on actin commonly called Blocked, Closed/Calcium and Open or Myosin states. These states are thought to correlate with different functional states of the contractile system: inactive-Ca-free, inactive-Ca-bound and active. The inactive-Ca-free state is highly occupied at low free Ca levels. However, saturating Ca produces a mixture of inactive and active states making study of the individual states difficult. Disease causing mutations of troponin, as well as phosphomimetic mutations change the stabilities of the states of the regulatory complex thus providing tools for studying individual states. Mutants of troponin are available to stabilize each of three structural states. Particular attention is given to the hypertrophic cardiomyopathy causing mutation, Δ14 of TnT, that is missing the last 14 C-terminal residues of cardiac troponin T. Removal of the basic residues in this region eliminates the inactive-Ca-free state. The major state occupied with Δ14 TnT at inactivating Ca levels resembles the inactive-Ca-bound state in function and in displacement of TnI from actin-tropomyosin. Addition of Ca, with Δ14TnT, shifts the equilibrium between the inactive-Ca-bound and the active state to favor that latter state. These mutants suggest a unique role for the C-terminal region of Troponin T as a brake to limit Ca activation.
PubMed: 35694406
DOI: 10.3389/fphys.2022.902079 -
Cardiovascular Research Sep 2016The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide... (Review)
Review
The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cyclin-Dependent Kinases; Genetic Predisposition to Disease; Humans; MicroRNAs; Proto-Oncogene Mas; Risk
PubMed: 27357636
DOI: 10.1093/cvr/cvw174 -
Journal of Cancer 2022Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the... (Review)
Review
Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the structural plasticity of dendrites and spines. Members of the Rho-GTPase family include Ras-related C3 botulinum toxin substrate 1 (Rac1), RhoA (Ras homologous), and cell division control protein 42 (Cdc42). Cdc42 is involved in the regulation of a variety of tumor and non-tumor diseases through a cascade of multiple signaling pathways. Active Cdc42 can regulate intercellular adhesion, cytoskeleton formation, and cell cycle, thus affecting cell proliferation, transformation, and dynamic balance as well as migration and invasion of tumor cells by regulating the expression of effector proteins. Here we discuss the role of Cdc42 in promoting metastasis, invasion, epithelial-mesenchymal transformation and angiogenesis in malignant tumors. The significant role of Cdc42 in non-tumor diseases is also discussed. Since Cdc42 plays a central role in the development of various diseases, small molecule inhibitors targeting Cdc42 have important clinical significance in the prevention and treatment of these diseases.
PubMed: 35154449
DOI: 10.7150/jca.65415 -
Frontiers in Pharmacology 2022Pulmonary fibrosis (PF) is a lung disease with no curative drug, characterized by a progressive decrease in lung function. Metformin (MET) is a hypoglycemic agent with...
Pulmonary fibrosis (PF) is a lung disease with no curative drug, characterized by a progressive decrease in lung function. Metformin (MET) is a hypoglycemic agent with the advantages of high safety and low cost and has been used in several trials to treat fibrotic diseases. This study aimed to explore the efficacy and safety of MET in treating PF and elaborate on its mechanism. Eight databases were searched for animal trials of MET for PF from the time of database creation until 1 March 2022. The risk of bias quality assessment of the included studies was conducted using SYRCLE's risk of bias assessment. Pulmonary inflammation and fibrosis scores were the primary outcomes of this study. Hydroxyproline (HYP), type I collagen (collagen I), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), Smad, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) protein expression in lung tissues and animal mortality were secondary outcomes. Effect magnitudes were combined and calculated using Revman 5.3 and Stata 16.0 to assess the efficacy and safety of MET in animal models of PF. Inter-study heterogeneity was examined using the or Q test, and publication bias was assessed using funnel plots and Egger's test. A total of 19 studies involving 368 animals were included, with a mean risk of bias of 5.9. The meta-analysis showed that MET significantly suppressed the level of inflammation and degree of PF in the lung tissue of the PF animal model. MET also reduced the content of HYP, collagen I, α-SMA, and TGF-β and phosphorylation levels of Smad2, Smad3, p-smad2/3/smad2/3, ERK1/2, and p-ERK1/2/ERK1/2 in lung tissues. MET also elevated AMPK/p-AMPK levels in lung tissues and significantly reduced animal mortality. The results of this study suggest that MET has a protective effect on lung tissues in PF animal models and may be a potential therapeutic candidate for PF treatment. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327285, identifier CRD42022327285.
PubMed: 36147352
DOI: 10.3389/fphar.2022.948101 -
Head and Neck Pathology Dec 2020The microenvironment of oral cancer is highly dynamic and has been proved to affect tumor progression. Pericytes are blood vessels surrounding cells that have recently...
The microenvironment of oral cancer is highly dynamic and has been proved to affect tumor progression. Pericytes are blood vessels surrounding cells that have recently gained attention for their roles in vascular and cancer biology. The objective of the present study was to survey the scientific literature for conclusive evidence about whether pericytes are part of blood vessels in oral squamous cell carcinoma (OSCC) and their roles in the tumor microenvironment and clinical outcomes. A systematic electronic search was undertaken in Medline Ovid, PubMed, Web of Science, and Scopus. Eligibility criteria were: publications adopting in vivo models of OSCC that included pericyte detection and assessment by pericyte markers (e.g., α-smooth muscle actin, neuron-glial antigen 2 and platelet-derived growth factor receptor-β). The search yielded seven eligible studies (from 2008 to 2018). The markers most commonly used for pericyte detection were α-smooth muscle actin and neuron-glial antigen 2. The studies reviewed showed the presence of immature vessels exhibiting a reduction of pericyte coverage in OSCC and indicated that anti-cancer therapies could contribute to vessel normalization and pericyte regain. The pericyte population is significantly affected during OSCC development and cancer therapy. While these findings might suggest a role for pericytes in OSCC progression, the limited data available do not allow us to conclude whether they modify the tumor microenvironment and clinical outcome.
Topics: Animals; Humans; Mouth Neoplasms; Pericytes; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 32506378
DOI: 10.1007/s12105-020-01188-2