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1.
Ecotoxicol Environ Saf ; 208: 111432, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33075588

RESUMO

Humans are exposed to phthalates ubiquitously, which may threaten health. However, whether di-n-octyl phthalate can prevent pubertal sexual maturity is still elusive. In this study, male Sprague Dawley rats (age 35 days) were treated daily by gavage with 0, 10, 100, and 1000 mg/kg body weight of di-n-octyl phthalate from day 35 to day 49 after birth. Di-n-octyl phthalate significantly reduced serum testosterone levels at doses of 100 and 1000 mg/kg, but increased serum luteinizing hormone levels of 1000 mg/kg and decreased testosterone/luteinizing hormone ratio at ≥10 mg/kg, without affecting serum follicle-stimulating hormone levels. Di-n-octyl phthalate significantly induced Leydig cell hyperplasia (increased number of CYP11A1-positive Leydig cells) at 100 and 1000 mg/kg. Di-n-octyl phthalate down-regulates the gene expression of Cyp11a1, Hsd3b1 and Insl3 in individual Leydig cells. Di-n-octyl phthalate can also reduce the number of sperm in the epididymis. Di-n-octyl phthalate increased phosphorylated AKT1/AKT2 without affecting their total proteins, but increased the total protein and phosphorylated protein of ERK1/2 and GSK-3ß. Primary immature Leydig cells isolated from 35-day-old rats were treated with 0-50 µM di-n-octyl phthalate for 3 h. This phthalate inhibited androgen production under basal, LH-stimulated, and cAMP-stimulated conditions by 5 and 50 µM in vitro via down-regulating Cyp11a1 expression but up-regulating Srd5a1 expression in vitro. In conclusion, di-n-octyl phthalate induces hypergonadotropic hypogonadism caused by Leydig cell hyperplasia but reduced steroidogenic function and prevents sperm production.


Assuntos
Substâncias Perigosas/toxicidade , Hipogonadismo/induzido quimicamente , Ácidos Ftálicos/toxicidade , Androgênios/metabolismo , Animais , Regulação para Baixo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patologia , Hipogonadismo/metabolismo , Hipogonadismo/patologia , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Hormônio Luteinizante/metabolismo , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Maturidade Sexual , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo , Regulação para Cima
2.
Int J Dermatol ; 60(1): 73-80, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33179785

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic multi-organ viral illness. Previous studies have found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the damage to vascular tissues are not well-elucidated yet. Histological data in COVID-19 patients are still limited and are mainly focused on post-mortem analysis. Given that the skin is affected by COVID-19 and the relative ease of its histological examination, we aimed to examine the histology of skin lesions in COVID-19 patients to better understand the disease's pathology. METHODS: Five skin lesions from COVID-19 adult patients were selected for a deep histological tissue examination. RESULTS: A strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cell growth was identified. Endothelial cell distortion generated vascular lumen obliteration and striking erythrocyte and serum extravasation. Significant deposition of C4d and C3 throughout the vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also observed. CONCLUSIONS: COVID-19 could comprise an obliterative microangiopathy consisting on endothelial and myointimal growth with complement activation. This mechanism, together with the increased vascular permeability identified, could contribute to obliteration of the vascular lumen and hemorrhage in COVID-19. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent increased risk of hemorrhage. Findings of this study could contribute to a better understanding of physiopathological mechanisms underlying COVID-19 on living patients and could help further studies find potential targets for specific therapeutic interventions in severe cases.


Assuntos
/complicações , Células Endoteliais/patologia , Miócitos de Músculo Liso/patologia , Dermatopatias/patologia , Doenças Vasculares/patologia , Idoso , Vasos Sanguíneos/patologia , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Endotélio/metabolismo , Endotélio/patologia , Humanos , Hiperplasia/patologia , Hiperplasia/virologia , Pele/irrigação sanguínea , Dermatopatias/virologia , Doenças Vasculares/virologia
3.
Toxicol Lett ; 334: 60-65, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961271

RESUMO

Iron oxides are Group 3 (not classifiable as to its carcinogenicity to humans) according to the International Agency for Research on Cancer (IARC). Occupational exposures during iron and steel founding and hematite underground mining as well as other iron predominant exposures such as welding are Group 1 (carcinogenic to humans). The objective of this study was to investigate the potential of iron as iron (III) oxide (Fe2O3) to initiate lung tumors in A/J mice, a lung tumor susceptible strain. Male A/J mice were exposed by oropharyngeal aspiration to suspensions of Fe2O3 (1 mg) or calcium chromate (CaCrO4; 100 µg; positive control) for 26 weeks (once per week). Shams were exposed to 50 µL phosphate buffered saline (PBS; vehicle). Mice were euthanized 70 weeks after the first exposure and lung nodules were enumerated. Both CaCrO4 and Fe2O3 significantly increased gross-observed lung tumor multiplicity in A/J mice (9.63 ± 0.55 and 3.35 ± 0.30, respectively) compared to sham (2.31 ± 0.19). Histopathological analysis showed that bronchiolo-alveolar adenomas (BAA) and carcinomas (BAC) were the primary lung tumor types in all groups and were increased in the exposed groups compared to sham. BAC were significantly increased (146 %) in the CaCrO4 group and neared significance in the Fe2O3 group (100 % increase; p = 0.085). BAA and other histopathological indices of toxicity followed the same pattern with exposed groups increased compared to sham control. In conclusion, evidence from this study, in combination with our previous studies, demonstrate that exposure to iron alone may be a potential risk factor for lung carcinogenesis.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Compostos de Cálcio/toxicidade , Carcinogênese/efeitos dos fármacos , Cromatos/toxicidade , Compostos Férricos/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Animais , Suscetibilidade a Doenças , Relação Dose-Resposta a Droga , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Soldagem
4.
Nat Commun ; 11(1): 4788, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963234

RESUMO

Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.


Assuntos
Proliferação de Células , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas Proto-Oncogênicas c-vav/genética , Proteínas Proto-Oncogênicas c-vav/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Diferenciação Celular , Modelos Animais de Doenças , Epiderme/metabolismo , Epiderme/patologia , GTP Fosfo-Hidrolases , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hiperplasia/patologia , Queratinócitos/patologia , Camundongos , Camundongos Knockout , Membrana Mucosa/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcriptoma
5.
Life Sci ; 260: 118412, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926924

RESUMO

AIMS: Rat models of duodenogastric reflux have been used to study gastric stump cancer (GSC), but the underlying molecular mechanisms are poorly understood. Unlike rats, mice can be genetically modified, providing a superior model for studying the molecular mechanisms underlying GSC development, which is associated with duodenogastric reflux. This study aimed at developing a mouse model of duodenogastric reflux. MAIN METHOD: C57BL/6 mice were randomly assigned to the control (n = 6), sham operation (n = 9), or gastrojejunostomy group (n = 12). Mice were sacrificed at 1, 3, and 6 months after surgery. Stomach tissue was stained with hematoxylin and eosin. Lesions were classified as chronic inflammation, intestinal metaplasia, or atypical hyperplasia. KEY FINDINGS: Nine mice underwent gastrojejunostomy without mortality. The animals in the gastrojejunostomy group exhibited chronic inflammation at 1, 3, and 6 months after surgery, showing intestinal metaplasia (n = 2) and atypical hyperplasia (n = 1) at 3 months and intestinal metaplasia (n = 2) and atypical hyperplasia (n = 2) at 6 months. The mice in the control group did not exhibit chronic inflammation or intestinal metaplasia, whereas those in the sham operation group exhibited chronic inflammation at 1, 3, and 6 months after surgery, without intestinal metaplasia or atypical hyperplasia. Intestinal metaplasia or atypical hyperplasia were more common in the gastrojejunostomy group than in the sham operation group (p = 0.012). SIGNIFICANCE: A duodenogastric reflux mouse model can be created using gastrojejunostomy without gastrectomy.


Assuntos
Modelos Animais de Doenças , Refluxo Duodenogástrico/patologia , Mucosa Gástrica/patologia , Hiperplasia/patologia , Inflamação/patologia , Animais , Refluxo Duodenogástrico/cirurgia , Gastrectomia , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Hiperplasia/imunologia , Hiperplasia/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Zhonghua Fu Chan Ke Za Zhi ; 55(7): 471-475, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842251

RESUMO

Objective: To explore the clinical characteristics of patients with pre-malignant or malignant transformation in ectopic endometrium of adenomyosis. Methods: A retrospective study was performed on 4 818 patients received surgical treatment in Peking Union Medical College Hospital and pathologically confirmed as adenomyosis from January 2010 to October 2016. The clinical features and prognosis of 30 patients among these with pre-malignant or malignant transformation in ectopic endometrium were reviewed. Results: A total of 4 818 patients pathologically diagnosed with adenomyosis. Among these,30 (0.62%,30/4 818) patients were diagnosed with pre-malignant or malignant transformation in foci of adenomyosis, including 16 (0.33%, 16/4 818) of atypical endometrial hyperplasia and 14 (0.29%, 14/4 818) of endometrioid carcinoma. The average age of 30 patients was (50.8±3.0) years (range: 27-65 years). Patients with atypical hyperplasia in foci of adenomyosis coexist with 13 cases of endometrioid carcinoma in situ, 1 case of borderline serous papilloma in eutopic endometrium, 1 case of atypical hyperplasia in eutopic endometrium, and 1 case of normal eutopic endometrium. Fourteen patients with endometrioid carcinoma in foci of adenomyosis coexist with endometrioid carcinoma in situ. Among the 27 patients with pre-malignant or malignant transformation in adenomyosis and coexisting with endometrioid carcinoma in situ, 23 of them were in International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰa (85%, 23/27), 2 in stage Ⅰb (7%, 2/27), and 2 in stage Ⅲa (7%, 2/27). Seven percent (2/27) of patients had deep myometrial infiltration, and 7% (2/27) of patients had lymphovascular space invasion. The median follow-up time was 60 months (range: 32-104 months), and there were no recurrence or death. Conclusions: The incidence of atypical glandular hyperplasia or malignant transformation in foci of adenomyosis is rare, and it may be closely related to endometrial disease in situ. Pre-malignant or malignant change in foci of adenomyosis seems not to increase the risk of deep myometrial invasion, lymphovascular space invasion, and recurrence or mortality in patients of adenomyosis with endometrial adenocarcinoma.


Assuntos
Adenomiose/patologia , Endométrio/patologia , Hiperplasia/patologia , Adulto , Idoso , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos
7.
Acta Cytol ; 64(6): 556-562, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32814324

RESUMO

OBJECTIVE: To investigate the cytological findings of lobular endocervical glandular hyperplasia (LEGH) associated with adenocarcinoma and to clarify its characteristics and the coexisting adenocarcinoma using histochemistry and immunohistochemistry. METHODS: Eighteen surgical cases of LEGH of the uterine cervix were retrospectively reviewed and classified into 3 groups: pure (pure type), atypical (atypical type), and LEGH with adenocarcinoma (mixed type). The mixed type is defined as LEGH or atypical LEGH with in situ or invasive adenocarcinoma. Cytological findings of conventional endocervical smear specimens (Papanicolaou stain) were analyzed. Histochemistry (periodic acid-Schiff reaction) and immunohistochemistry (M-GGMC-1, Muc-6 glycoprotein, and Ki-67) were performed using tissue specimens. RESULTS: Cytologically, the pure type (7 cases) is characterized by glandular cell clusters that tended to form monolayered sheets with uniformly small nuclei and contain golden-yellowish mucin, whereas atypical (5 cases) and mixed (6 cases) types are characterized by glandular cell clusters similar to those of the pure type, but with complex glandular structures and mucin localization on the surface of glandular cell clusters. Ki-67 labeling index was significantly higher in atypical and mixed types than that in the pure type. Gastric-type mucinous carcinoma (MC-G) was observed in 2 out of 6 cases with mixed type. CONCLUSIONS: LEGH is found to be associated with adenocarcinoma types other than MC-G. Complex glandular structures or mucin localization on the surface of glandular cell clusters may be useful cytological findings to detect atypical and mixed types of LEGH.


Assuntos
Adenocarcinoma/patologia , Colo do Útero/patologia , Hiperplasia/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Mucinas/metabolismo
8.
Br J Radiol ; 93(1115): 20200135, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32816520

RESUMO

For many individuals, the term 'cancer' equates to a disease that if untreated will progress, spread from the area initially affected and ultimately cause death. 'Breast cancer', however, is a diverse of range of pathological entities, incorporating indolent to fast-growing and aggressive lesions, with varying histological patterns, clinical presentations, treatment responses and outcomes. Screening for malignancy is based on the assumption that cancer has a gradual, orderly progression and that detecting lesions earlier in their natural history, and intervening, will reduce mortality. The natural history of epithelial atypia, ductal carcinoma in situ and even invasive breast cancer is poorly understood, but widely variable. We believe that population breast screening methodology needs to change to focus on diagnosis of lesions of greatest clinical relevance.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Programas de Rastreamento/métodos , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/genética , Progressão da Doença , Detecção Precoce de Câncer , Feminino , Perfilação da Expressão Gênica , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Programas de Rastreamento/efeitos adversos
10.
PLoS One ; 15(8): e0235634, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760078

RESUMO

Otitis media, the most common disease of childhood, is characterized by extensive changes in the morphology of the middle ear cavity. This includes hyperplasia of the mucosa that lines the tympanic cavity, from a simple monolayer of squamous epithelium into a greatly thickened, respiratory-type mucosa. The processes that control this response, which is critical to otitis media pathogenesis and recovery, are incompletely understood. Given the central role of protein phosphorylation in most intracellular processes, including cell proliferation and differentiation, we screened a library of kinase inhibitors targeting members of all the major families in the kinome for their ability to influence the growth of middle ear mucosal explants in vitro. Of the 160 inhibitors, 30 were found to inhibit mucosal growth, while two inhibitors enhanced tissue proliferation. The results suggest that the regulation of infection-mediated tissue growth in the ME mucosa involves multiple cellular processes that span the kinome. While some of the pathways and processes identified have been previously implicated in mucosa hyperplasia others are novel. The results were used to generate a global model of growth regulation by kinase pathways. The potential for therapeutic applications of the results are discussed.


Assuntos
Proliferação de Células/efeitos dos fármacos , Otite Média/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Haemophilus influenzae/patogenicidade , Ensaios de Triagem em Larga Escala , Humanos , Hiperplasia/tratamento farmacológico , Hiperplasia/microbiologia , Hiperplasia/patologia , Camundongos , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/microbiologia , Membrana Mucosa/patologia , Otite Média/microbiologia , Otite Média/patologia , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Ratos , Técnicas de Cultura de Tecidos
11.
Mod Pathol ; 33(11): 2139-2146, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32620916

RESUMO

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.


Assuntos
Infecções por Coronavirus/patologia , Histiócitos/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/virologia , Pneumonia Viral/patologia , /virologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Medula Óssea/patologia , Feminino , Humanos , Hiperplasia/patologia , Hiperplasia/virologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pandemias
12.
Spec Care Dentist ; 40(5): 506-510, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32691895

RESUMO

OBJECTIVE: The objective of this study is to report the case of a patient who underwent hematopoietic stem cell transplantation for Hodgkin's lymphoma treatment and developed multiple tongue lesions during recovery. METHODS AND RESULTS: This is the case report of a patient who developed ulcerated lesions with areas of depapillation on the border and dorsum of the tongue. The ulcer evolved to a reddish fibrous hyperplastic nodule, similar to adjacent mucosa. The patient was using a series of medications, such as antifungals, antibiotics, antivirals, corticosteroids, and analgesics in addition to immunosuppression with cyclosporine. Considering the medical history of the patient, a biopsy was performed. Histopathological analyses describe hyperplasia, granulation tissue, vascular proliferation, and intense inflammatory infiltrate, and the diagnosis was of medication-related fibrovascular hyperplasia (MRFH). CONCLUSION: Patients in use of cyclosporine are at risk to develop oral lesions, such as MRFH. The correct diagnosis is important, so the adequate treatment and follow-up are instituted even considering the immunosuppression protocol.


Assuntos
Úlceras Orais , Doenças da Língua , Biópsia , Humanos , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Úlceras Orais/patologia , Língua , Doenças da Língua/induzido quimicamente , Doenças da Língua/diagnóstico , Doenças da Língua/patologia
13.
Int J Oral Maxillofac Surg ; 49(11): 1435-1438, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32653260

RESUMO

The aim of this study was to describe the steps of a minimally invasive surgical technique used to perform a proportional intraoral condylectomy with a three-dimensionally (3D) printed cutting guide. The technique consists of two steps: virtual surgical planning and intraoral condylectomy. During virtual surgical planning, the mandibular ramus was measured bilaterally, the height of the proportional condylectomy was planned virtually, and a cutting guide was 3D printed. In the intraoral condylectomy, the mandibular condyle was approached intraorally, the 3D printed cutting guide was positioned in the sigmoid notch, and the proportional condylectomy was performed. The protocol reported in this technical note is the sum of knowledge acquired from a series of studies published previously by the authors, who have jointly developed a surgical technique that is both minimally invasive and accurate for the treatment of condylar hyperplasia.


Assuntos
Côndilo Mandibular , Osteotomia , Assimetria Facial/patologia , Humanos , Hiperplasia/patologia , Mandíbula , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/patologia , Côndilo Mandibular/cirurgia , Impressão Tridimensional
14.
PLoS One ; 15(6): e0225173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603328

RESUMO

Vascular hyperplasia after vascular trauma is one of the difficult problems in clinical treatment. Nowadays, there is no effective treatment for vascular hyperplasia. Previous studies have shown that integrinß1 andß3 activity play an important role in vascular hyperplasia. Kindlin-2 has been shown to modulate integrinß1 andß3 activity in cancer. Therefore, in this study, we hope to explore the relationship between Kindlin-2 and vascular hyperplasia. We overexpressed or knocked down Kindlin-2 by adenovirus. The results showed that Kindlin-2 overexpression could regulate integrinß1 andß3 activity through FAK-PIK3 signaling pathways ex vivo and in vivo, thereby affecting the proliferation and migration of VSMC, and then it causes the consequences of vascular hyperplasia. Therefore, Our results show that Kindlin-2 may be a potential target for the treatment of vascular hyperplasia.


Assuntos
Movimento Celular , Quinase 1 de Adesão Focal/metabolismo , Integrina beta1/metabolismo , Integrina beta3/metabolismo , Proteínas de Membrana/metabolismo , Músculo Liso Vascular/citologia , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Animais , Proliferação de Células , Técnicas de Silenciamento de Genes , Hiperplasia/metabolismo , Hiperplasia/patologia , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Ratos
15.
Oral Maxillofac Surg ; 24(4): 515-520, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32621034

RESUMO

INTRODUCTION: Elongated mandibular coronoid process is a rare condition defined as enlargement of the coronoid process. The only useful way to treat the mouth-opening limitation is resection of the elongated coronoid process. Four-dimensional CT (4DCT; three spatial dimensions plus time axis) is a novel imaging technique. Its usefulness of for evaluation of dynamic movements such as joint motion has been reported. Here, we show the potential usefulness of 4DCT evaluation in a patient with elongated mandibular coronoid process. CASE PRESENTATION: A 59-year-old female who suffered from mouth-opening difficulty and pressure during mouth opening was referred to our department. Elongation of the right coronoid process was evident in a panoramic X-ray image. The mandibular movement and temporal muscle motility before and after coronoidectomy in this patient on 4DCT could be evaluated. CONCLUSIONS: 4DCT is useful in the diagnosis and surgical outcome of elongated coronoid process.


Assuntos
Tomografia Computadorizada Quadridimensional , Osteotomia Mandibular , Feminino , Humanos , Hiperplasia/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Mandíbula/cirurgia , Pessoa de Meia-Idade , Radiografia Panorâmica
16.
Medicine (Baltimore) ; 99(29): e21103, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702858

RESUMO

RATIONALE: Lymphadenectomy for tongue cancer in the neck region is often accompanied by local impaired mobility, gland damage, difficult in swallowing, and postoperative complication and seriously affects patients life quality. We reported a case of subcutaneous adhesions and scar hyperplasia in the neck region after lymphadenectomy for tongue lesions accompanied by impaired neck mobility and difficult in swallowing was treated using Fu's subcutaneous needling (FSN) treatment. PATIENT CONCERNS: A 55-year-old male with tongue cancer received surgical intervention with lymphadenectomy 8 years ago was revealed a 15 cm-long curved surgical incision in the neck region and surrounded by numerous scar tissues. DIAGNOSIS: Post-operation subcutaneous adhesions and scar hyperplasia in the neck region after lymphadenectomy was diagnosed. INTERVENTIONS: FSN treatment was performed 2 to 3 times per week for 1 month to sway the affected tightened muscle and dissociate the superficial fascia beneath the scar resulted in a considerable improvement in neck movement. OUTCOMES: The Vancouver Scar Scale (VSS) was as follows: color (M) - 1; vascular distribution (V) - 0, thickness (H) - 2, and flexibility (P) - 4, with a total of 7 points before FSN treatment. The VSS after 1 month of FSN treatment was as follows: M1, V0, H2, and P2, with a total of 5 points. Neck mobility in different directions, i.e., stretching to the back of the neck and laterally bending the neck to the left and/or right side, was improved (P < .05). LESSONS: At present, treatment of chronic scar hyperplasia has certain side effects and limitations. FSN is safe and convenient, with minimal destruction of the superficial fascia, having evident effects of dissociating tissue adhesion under scars and compensating for deficiencies in scar hyperplasia treatment. It can provide new ideas for future treatments.


Assuntos
Hiperplasia/terapia , Pescoço/anormalidades , Tela Subcutânea/anormalidades , Aderências Teciduais/terapia , Humanos , Hiperplasia/patologia , Hiperplasia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pescoço/fisiopatologia , Tela Subcutânea/patologia , Tela Subcutânea/fisiopatologia , Aderências Teciduais/patologia , Aderências Teciduais/fisiopatologia , Neoplasias da Língua/complicações , Neoplasias da Língua/fisiopatologia , Neoplasias da Língua/cirurgia
17.
J Vis Exp ; (159)2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32478716

RESUMO

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor because of the acceleration of intimal hyperplasia due to the exposure to arterial blood pressure. The present protocol is designed for the establishment of experimental venous intimal hyperplasia by interposing rabbit jugular veins to the ipsilateral carotid arteries. The protocol does not require surgical procedures deep in the body trunk and the extent of the incision is limited, which is less invasive for the animals, allowing long-term observation after implantation. This simple procedure enables researchers to investigate strategies to attenuate the progression of intimal hyperplasia of the implanted vein grafts. Using this protocol, we reported the effects transduction of microRNA-145 (miR-145), which is known to control the phenotype of vascular smooth muscle cells (VSMCs) from the proliferative to the contractile state, into harvested vein grafts. We confirmed the attenuation of intimal hyperplasia of vein grafts by transducing miR-145 before implantation surgery through the phenotype change of the VSMCs. Here we report a less invasive experimental platform to investigate the strategies that can be used to attenuate intimal hyperplasia of vein grafts in revascularization surgeries.


Assuntos
Pressão Arterial/fisiologia , Hiperplasia/patologia , Túnica Íntima/patologia , Túnica Íntima/fisiopatologia , Procedimentos Cirúrgicos Vasculares/métodos , Veias/transplante , Animais , Modelos Animais de Doenças , Coelhos
18.
Am J Pathol ; 190(9): 1843-1858, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32479820

RESUMO

The progression of Crohn disease to intestinal stricture formation is poorly controlled, and the pathogenesis is unclear, although increased smooth muscle mass is present. A previously described rat model of trinitrobenzenesulfonic acid-induced colitis is re-examined here. Although inflammation of the mid-descending colon typically resolved, a subset showed characteristic stricturing by day 16, with an inflammatory infiltrate in the neuromuscular layers including eosinophils, CD3-positive T cells, and CD68-positive macrophages. Closer study identified CD163-positive, CD206-positive, and arginase-positive cells, indicating a M2 macrophage phenotype. Stricturing involved ongoing proliferation of intestinal smooth muscle cells (ISMC) with expression of platelet-derived growth factor receptor beta and progressive loss of phenotypic markers, and stable expression of hypoxia inducible factor 1 subunit alpha. In parallel, collagen I and III showed a selective and progressive increase over time. A culture model of the stricture phenotype of ISMC showed stable hypoxia inducible factor 1 subunit alpha expression that promoted growth and improved both survival and growth in models of experimental ischemia. This phenotype was hyperproliferative to serum and platelet-derived growth factor BB, and unresponsive to transforming growth factor beta, a prominent cytokine of M2 macrophages, compared with control ISMC. We identified a hyperplastic phenotype of ISMC, uniquely adapted to an ischemic environment to drive smooth muscle layer expansion, which may reveal new targets for treating intestinal fibrosis.


Assuntos
Doença de Crohn/patologia , Intestinos/patologia , Macrófagos/metabolismo , Músculo Liso/patologia , Animais , Constrição Patológica/induzido quimicamente , Constrição Patológica/patologia , Hiperplasia/induzido quimicamente , Hiperplasia/metabolismo , Hiperplasia/patologia , Músculo Liso/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fenótipo , Ratos , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico/toxicidade
19.
Intern Med ; 59(16): 2029-2034, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32493848

RESUMO

In the 2013 updated classification of the American Thoracic Society/European Respiratory Society, airway-centered interstitial fibrosis (ACIF) is included as a bronchiolocentric pattern of interstitial pneumonia (IP) among idiopathic IPs. We encountered a case of severe pulmonary hypertension (PH) with chronic IP. The patient initially presented with shortness of breath and often lost consciousness due to PH, and seven years after his first visit, he ultimately died. An autopsy revealed ACIF and usual IP. In particular, the ACIF comprised non-atypical smooth muscle hyperplasia, and pulmonary hypertensive vascular degeneration was detected. This case may represent a new pathological feature of ACIF.


Assuntos
Broncopatias/complicações , Hipertensão Pulmonar/complicações , Doenças Pulmonares Intersticiais/complicações , Idoso , Broncopatias/patologia , Dispneia/patologia , Fibrose , Humanos , Hiperplasia/patologia , Hipertensão Pulmonar/patologia , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Músculo Liso/patologia
20.
EBioMedicine ; 57: 102833, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32574956

RESUMO

BACKGROUND: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a series of clinical symptoms and severe illnesses, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. METHODS: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining was performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. FINDINGS: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. INTERPRETATION: Infection of alveolar macrophage by SARS-CoV-2 might be drivers of the "cytokine storm", which might result in damages in pulmonary tissues, heart and lung, and lead to the failure of multiple organs . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China.


Assuntos
Células Epiteliais Alveolares/patologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Pulmão/patologia , Macrófagos Alveolares/patologia , Pneumonia Viral/patologia , Autopsia , Betacoronavirus , China , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/mortalidade , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Hiperplasia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/mortalidade , Glicoproteína da Espícula de Coronavírus/metabolismo
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