RESUMO
Claudins are one of the major components of tight junctions (TJs) that polymerize within the cell membrane and form interactions between cells. Some claudins seal the paracellular space, limiting paracellular flux, while others form selectively permeable ion channels that control the paracellular permeability of small ions. Claudin strands are known to be dynamic and reshape within TJs to accommodate large-scale movements and rearrangements of epithelial tissues. Here, we summarize the recent computational and modeling studies on claudin assembly into tetrameric ion channels and their polymerization into µm long strands within the membrane. Computational studies ranging from all-atom molecular dynamics, coarse-grained simulations, and hybrid-resolution simulations elucidate the molecular nature of claudin assembly and function and provide a framework that describes the lateral flexibility of claudin strands.
Assuntos
Claudinas , Junções Íntimas , Claudinas/metabolismo , Junções Íntimas/metabolismo , Canais Iônicos/metabolismo , Simulação de Dinâmica Molecular , Epitélio/metabolismo , Claudina-3/metabolismoRESUMO
Idiopathic Granulomatous Mastitis (IGM) is an uncommon inflammatory disease of the breast, with similar presentations as breast cancer and a relatively high recurrence rate. We reviewed the demographics, clinical presentations, and treatment modalities of a large cohort of patients in Iran. Most of the patients had history of pregnancy and breastfeeding. The most common clinical finding was pain and a palpable mass, respectively. Most of the patients received medical treatment, and about half of the patients had surgery. The recurrence rate was 24.8%, and breast skin lesions were associated with a significantly higher odds of recurrence.
Assuntos
Neoplasias da Mama , Mastite Granulomatosa , Aleitamento Materno , Feminino , Mastite Granulomatosa/diagnóstico por imagem , Mastite Granulomatosa/cirurgia , Humanos , Irã (Geográfico) , Recidiva Local de Neoplasia , Gravidez , RecidivaRESUMO
Breast sarcoma is a rare but aggressive tumor. There are few case reports in the literature and several aspects of this disease are still not completely comprehended. Therefore, reporting new cases can help to enrich the literature. We report a patient with breast mass and pus secretion from her right breast, misdiagnosed as an abscess and mistreated by antibiotics. The patient was referred for an ultrasound examination and mammography, and a needle biopsy was performed that suggested an aggressive tumor. By the pathologist's suggestion, a total mastectomy of the right breast was performed with the excision of sentinel nodes. A pathological examination revealed a high-grade undifferentiated pleomorphic sarcoma (UPS) without vascular or lymph node invasion as the final diagnosis. The patient underwent postoperative chemotherapy and is currently in good condition. This case emphasizes considering this rare tumor when approaching a breast mass. Performing surgery with adequate resection margin can improve the patient's prognosis. Some suggested breast UPS cases with lung and brain metastasis would be more aggressive tumors than other breast sarcomas. Total mastectomy with negative margins and free-of-tumor lymph nodes may be the key to improve prognosis in such patients.
RESUMO
The Claudin-15 (CLDN15) channel is important for nutrient, electrolyte, and water transport in the gastrointestinal tract. We used cell culture studies and molecular dynamics simulations to elucidate its structure and permeability mechanisms. We provide a model that underscores the crucial role of the D55 residue in the CLDN15 selectivity filter, which interacts with permeating cations. Our studies demonstrated the mechanisms whereby the size and charge of the D55 residue influence paracellular permeability. By altering D55 to larger, negatively charged glutamic acid (E) or similarly sized neutral asparagine (N), we observed changes in pore size and selectivity, respectively. D55E mutation decreased pore size, favoring small ion permeability without affecting charge selectivity, while D55N mutation led to reduced charge selectivity without markedly altering size selectivity. These findings shed light on the complex interplay of size and charge selectivity of CLDN15 channels. This knowledge can inform the development of strategies to modulate the function of CLDN15 and similar channels, which has implications for tight junction modulation in health and disease.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Compostos de Organotecnécio/uso terapêutico , Radiografia Intervencionista/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Albumina Sérica/uso terapêuticoRESUMO
The recent coronavirus disease 2019 (COVID-19) significantly affected many people worldwide, especially those with underlying diseases. While some people with underlying illnesses, including cardiovascular diseases, are more vulnerable to develop severe COVID-19, other populations, including people who have autoimmune diseases, may develop severe diseases similar to the general population. The severity and outcome of COVID-19 are reviewed in individuals with underlying viral diseases, including acquired immune deficiency syndrome and hepatitis, however, some infectious diseases, including human T-lymphotropic virus type 1 (HTLV-1) diseases, is under-reported in the literature. HTLV-1 is a sexually transmitted disease that is endemic in some parts of the world. Infected patients may develop clinical symptoms of HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia (ATL) or may remain asymptomatic during their life. To the best of our knowledge, no clinical studies evaluate the severity and outcomes of SARS-CoV-2 infection in HTLV-1 infected patients. We aimed to review the pathogenesis of both of these viral infections and discuss their similarities in provoking immune responses. Although HTLV-1 infected patients may have had variable degrees of inflammation and immune system dysregulation, the available data is limited to conclude that HTLV-1 infected patients may be more vulnerable to developing severe COVID-19 in contrast to the general population.