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Scientific Reports Jul 2024Cancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the...
Cancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the most common ailments worldwide, indicating the importance of developing particular techniques that could help attenuate the effects of breast cancer and related outcomes. The primary aim of the current study was to review the role of inflammatory and stress markers in the development and progression of breast cancer. Four hundred ninety-eight (n = 498) patients with breast cancer and four hundred and ninety-eight (n = 498) age- and sex-matched controls were selected for this case‒control study. Serum samples were obtained, and the levels of stress and inflammatory markers, including Matrix metalloproteases (MMPs), Interleukins (ILs), Heat shock proteins (HSPs), Malondialdehyde (MDA), Nitric Oxide (NO), inducible Nitric Oxide Synthase (iNOS) and Tumour necrosis factor-alpha (TNF-α), were determined. Most (62%) patients had metastatic breast cancer (stage III or IV) with an adverse grade (65% with Grade III and 35% with Grade II). The present study showed that the levels of oxidants such as MDA, ILs, MMPs and HSPs were significantly greater, while the levels of antioxidants such as Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), vitamin A, C and D were significantly lower in breast cancer patients than in controls, suggesting their diagnostic importance and role in the pathophysiology of breast cancer. Oxidants, including IL-1, HSP27 and MMP9, which are highly specific and sensitive, may be used to develop the pathophysiological pathways of metastatic breast cancer in these patients. These pathways include cell invasion, cell migration and epithelial-mesenchymal transition. Therefore, we concluded that an increase in growth factors, e.g., Vascular Endothelial Growth Factor (VEGF), Tumour Growth Factor-beta (TGF-β) and B-cell lymphoma (Bcl2), under the influence of these variables plays a crucial role in the metastasis of breast cancer.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Adult; Biomarkers, Tumor; Case-Control Studies; Inflammation; Oxidative Stress; Malondialdehyde; Nitric Oxide
PubMed: 38956273
DOI: 10.1038/s41598-024-65821-8 -
European Journal of Haematology Jul 2024Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease....
Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0-19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12-39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18-46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.
PubMed: 38955806
DOI: 10.1111/ejh.14261 -
Laryngo- Rhino- Otologie Jul 2024
Topics: Humans; Dysphonia; Botulinum Toxins, Type A; Pain Perception; Injections, Intramuscular; Neuromuscular Agents
PubMed: 38955149
DOI: 10.1055/a-2226-0970 -
Laryngo- Rhino- Otologie Jul 2024
Topics: Humans; Dysphonia; Botulinum Toxins, Type A; Injections, Intramuscular; Pain Perception; Female; Middle Aged
PubMed: 38955148
DOI: 10.1055/a-2226-0626 -
Calcified Tissue International Jul 2024Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to...
Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to explore the role and underlying molecular mechanisms of Yes-associated protein (YAP) in rat ankle osteoarthritis. The results demonstrated that YAP expression levels were abnormally increased in the ankle osteoarthritis cartilage model. In addition, knockdown of YAP expression was shown to hinder the imbalance in ECM metabolism induced by IL-1β in chondrocytes, as demonstrated by the regulation of matrix metalloproteinase (MMP)-3, MMP-9, and MMP-13, a disintegrin, metalloprotease with thrombospondin motifs, aggrecan, and collagen II expression. Additional studies revealed that downregulation of YAP expression markedly inhibited the overexpression of β-catenin stimulated by IL-1β. Furthermore, inhibition of the Wnt/β-catenin signaling pathway reversed the ECM metabolism imbalance caused by YAP overexpression in chondrocytes. It is important to note that the YAP-specific inhibitor verteporfin (VP) significantly delayed the progression of ankle osteoarthritis. In conclusion, the findings highlighted the crucial role of YAP as a regulator in modulating the progression of ankle osteoarthritis via the Wnt/β-catenin signaling pathway. These findings suggest that pharmacological inhibition of YAP can be an effective and critical therapeutic target for alleviating ankle osteoarthritis.
PubMed: 38953964
DOI: 10.1007/s00223-024-01242-z -
Infection and Immunity Jul 2024α-hemolysin (Hla) is a pore-forming toxin critical for the pathogenesis of skin and soft tissue infections, which causes the pathognomonic lesion of cutaneous necrosis...
α-hemolysin (Hla) is a pore-forming toxin critical for the pathogenesis of skin and soft tissue infections, which causes the pathognomonic lesion of cutaneous necrosis (dermonecrosis) in mouse models. To determine the mechanism by which dermonecrosis develops during skin infection, mice were given control serum, Hla-neutralizing antiserum, or an inhibitor of Hla receptor [A-disintegrin and metalloprotease 10 (ADAM10) inhibitor] followed by subcutaneous infection by and the lesions were evaluated using immunohistochemistry and immunofluorescence. Hla induced apoptosis in the vascular endothelium at 6 hours post-infection (hpi), followed by apoptosis in keratinocytes at 24 hpi. The loss of vascular endothelial (VE)-cadherin expression preceded the loss of epithelial-cadherin expression. Hla also induced hypoxia in the keratinocytes at 24 hpi following vascular injury. Treatment with Hla-neutralizing antibody or ADAM10 inhibitor attenuated early cleavage of VE-cadherin, cutaneous hypoxia, and dermonecrosis. These findings suggest that Hla-mediated vascular injury with cutaneous hypoxia underlies the pathogenesis of -induced dermonecrosis.
PubMed: 38953668
DOI: 10.1128/iai.00133-24 -
The Chinese Journal of Dental Research Jun 2024As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular... (Review)
Review
As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular matrix (ECM) in the periodontal ligament (PDL). The ECM of the PDL consists of various types of collagens and other glycoproteins. The specific process and mechanism of ECM remodelling during orthodontic tooth movement remains unclear. Collagen I and III, which constitute major components of the PDL, are upregulated under orthodontic force. The changes in the contents of ECM proteins also depend on the expression of ECM-related enzymes, which organise new collagen fibre networks to adapt to changes in tooth position. The matrix metalloproteinase family is the main enzyme that participates in collagen hydrolysis and renewal and changes its expression under orthodontic force. Moreover, ECM adhesion molecules, such as integrins, are also regulated by orthodontic force and participate in the dynamic reaction of cell adhesion and separation with the ECM. This article reviews the changes in ECM components, related enzymes and adhesion molecules in the PDL under orthodontic force to lay the foundation for the exploration of the regulatory mechanism of ECM remodelling during orthodontic tooth movement.
Topics: Extracellular Matrix; Humans; Tooth Movement Techniques; Periodontal Ligament; Periodontium; Matrix Metalloproteinases; Integrins; Collagen
PubMed: 38953477
DOI: 10.3290/j.cjdr.b5459583 -
Journal of Obstetrics and Gynaecology :... Dec 2024The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth.
METHODS
On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software.
RESULTS
A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01).
CONCLUSIONS
The inflammatory biomarkers IL-1β, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.
Topics: Humans; Amniotic Fluid; Female; Pregnancy; Premature Birth; Biomarkers; Interleukin-6; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Inflammation; Matrix Metalloproteinase 9; Interleukin-10
PubMed: 38952221
DOI: 10.1080/01443615.2024.2368764 -
BMC Oral Health Jun 2024Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible... (Comparative Study)
Comparative Study
OBJECTIVE
Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease.
SUBJECTS AND METHODS
The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group.
RESULTS
Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252).
CONCLUSION
These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.
Topics: Humans; Matrix Metalloproteinase 9; Lichen Planus, Oral; Galectin 3; Hypoxia-Inducible Factor 1, alpha Subunit; Female; Male; Middle Aged; Galectins; Adult; Cell Transformation, Neoplastic; Epithelial Cells; Case-Control Studies; Immunohistochemistry; Blood Proteins
PubMed: 38951854
DOI: 10.1186/s12903-024-04457-6 -
BMJ Open Jul 2024Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal... (Observational Study)
Observational Study
Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity.
INTRODUCTION
Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting.
METHODS AND ANALYSIS
The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality.
ETHICS AND DISSEMINATION
This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
NCT05379413.
Topics: Humans; Muscle Spasticity; Botulinum Toxins, Type A; Prospective Studies; Neuromuscular Agents; Upper Extremity; Longitudinal Studies; Stroke; Stroke Rehabilitation; Observational Studies as Topic; Female; Male
PubMed: 38950995
DOI: 10.1136/bmjopen-2024-085484