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1.
J Surg Res ; 282: 147-154, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36274449

RESUMO

INTRODUCTION: Although imaging plays no role in diagnosing primary hyperparathyroidism (PHPT), preoperative localization is essential for a focused parathyroidectomy. We hypothesized that reviewing imaging obtained prior to PHPT diagnosis can identify enlarged parathyroid glands and provide information that might potentially impact the preoperative evaluation and intraoperative course of patients undergoing parathyroidectomy. METHODS: We included adult patients with PHPT who underwent parathyroidectomy between October 2015 and October 2020 and had contrast-enhanced computed tomography (CT) imaging of the lower neck and upper chest obtained prior to diagnosis for unrelated indications. A radiologist reviewed the prediagnosis CTs blinded to subsequent parathyroid localization imaging and operative findings. A surgeon assessed the radiologist's findings in the context of each case to determine the potential impact of information from old imaging on surgical decision-making. RESULTS: We identified at least one enlarged parathyroid gland on prior contrast-enhanced CT in 30 (75%) of 40 included patients. Despite old imaging enabling correct localization, 60% of these 30 underwent dedicated parathyroid imaging prior to parathyroidectomy. Knowledge of the enlarged parathyroid(s) on prior imaging might have allowed a more focused approach in 10.0% and prompted a more thorough exploration in 13.3%. In the total cohort, reviewing prior imaging could have provided information capable of changing the preoperative evaluation in 52.5% and the operative course in 17.5%. CONCLUSIONS: The identification of enlarged parathyroid glands on contrast-enhanced CT imaging that predates a diagnosis of PHPT is possible. Prospective studies might verify the impact of these findings on the preoperative evaluation and operative course of patients undergoing parathyroidectomy.


Assuntos
Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Adulto , Humanos , Paratireoidectomia/métodos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/patologia , Neoplasias das Paratireoides/cirurgia , Estudos Prospectivos , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/cirurgia , Glândulas Paratireoides/patologia , Tomografia Computadorizada por Raios X , Hiperplasia/patologia , Hormônio Paratireóideo , Estudos Retrospectivos
2.
Eur J Gastroenterol Hepatol ; 35(1): 59-63, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468570

RESUMO

OBJECTIVE: Postinfectious irritable bowel syndrome (IBS) is a known entity. We evaluated the incidence of post-COVID-19 IBS in patients discharged from the hospital and analyzed its correlation with the clinical and laboratory parameters, and treatment during the hospital stay. METHODS: Three hundred three COVID-19 hospitalized patients without prior history of IBS were prospectively followed after their discharge and were evaluated as per Rome-IV criteria for IBS. RESULTS: One hundred seventy-eight patients were males (58.7%). The age range was 17-95 years (mean ± SD, 55.9 ± 15.8). A total of 194 (64%) had mild COVID-19, 74 (24.4%) had moderate COVID-19, whereas 35 (11.6%) had severe COVID-19 infection. Sixteen (5.3%) patients had concomitant GI symptoms during COVID-19 infection. IBS symptoms were found to be present in 32 (10.6%) patients, out of which 17 (53.13%) had diarrhea-predominant, 10 (31.25%) had constipation-predominant, and five (15.62%) had mixed-type IBS. Post-COVID-19 IBS was more common in the female sex (P < 0.001), concomitant GI symptoms with COVID-19 (P < 0.001), oxygen requirement (P = 0.015), deranged liver function tests at the time of admission (P = 0.002), high procalcitonin (P = 0.013), high C-reactive protein levels (P = 0.035); whereas negative correlation was found with remdesivir treatment (P = 0.047). After performing regression analysis, female sex (P < 0.001), oxygen requirement during hospital stay (P = 0.016), GI symptoms during COVID-19 infection (P < 0.001), and high procalcitonin levels (P = 0.017) were independently associated with post-COVID-19 IBS. CONCLUSION: GI symptoms during active COVID-19 infection increase the chances of developing post-COVID-19 IBS. The risk of developing post-COVID-19 IBS increases in female patients, those requiring oxygen and having high procalcitonin levels during COVID-19 infection.


Assuntos
COVID-19 , Síndrome do Intestino Irritável , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Incidência , Síndrome do Intestino Irritável/epidemiologia , Pró-Calcitonina , COVID-19/complicações , COVID-19/epidemiologia , Hiperplasia , Causalidade
3.
Parasitol Int ; 92: 102656, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36007704

RESUMO

Allied to the problem of gastrointestinal parasites, especially Haemochus contortus, the use of lectins of plant origin has contributed to the research of alternative anthelmintics. The nematicidal effect of a water soluble Moringa oleifera lectin (WSMoL) was investigated in an experimental model with H. contortus infected Wistar rodents. Three concentrations were tested orally: 5 mg/kg, 2.5 mg/kg and 1 mg/kg. The reduction in the number of larvae recovered in the experimental groups was analyzed, as well as biochemical, hematological and histological parameters. Treatments with 5, 2.5 and 1 mg/kg of WSMoL reduced the number of larvae recovered of animals by 74.7 %, 72.8 % and 66 %, respectively. Untreated infected animals had anemia, moderate mononuclear multifocal hepatitis, vascular congestion in the liver and kidneys, white pulp hyperplasia in the spleen, and presence of eosinophils in the intestine. Infected animals treated with 5 mg/kg of WSMoL showed liver with moderate bleeding, kidney with vascular congestion, spleen with white pulp hyperplasia and intestine with moderate presence of mononuclear cells. An increase in the serum level of glutamic pyruvic transaminase and a reduction in the level of hemoglobin (p < 0.001) were also observed in this group when compared to the uninfected group. However, the administered concentrations of 2.5 and 1 mg/kg of WSMoL were both satisfactory in terms of reducing the number of recovered larvae and not promoting negative changes in the biochemical, hematological and histological parameters evaluated. These results indicate an in vivo nematicidal effect of WSMoL on the H. contortus parasite.


Assuntos
Anti-Helmínticos , Haemonchus , Moringa oleifera , Animais , Lectinas , Roedores , Água , Hiperplasia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Antinematódeos , Larva
4.
J Ethnopharmacol ; 300: 115723, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36115600

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs "taken orally after soaked with Chinese Baijiu" in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear. AIM OF THE STUDY: To analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu". MATERIALS AND METHODS: Ultra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats. RESULTS: The identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-ß-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-ß-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the Cmax and AUC0-t of muscone and aconitine in XJP&B were higher, and the T1/2 and MRT0-t of 3-acetyl-11-keto-ß-boswellic acid in XJP&B were relatively longer. CONCLUSION: This research proved that "taking XJPs orally after being soaked with Chinese Baijiu" can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu", which can provide a theoretical basis for the optimization of XJPs' clinical administration method.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Ácido Oleanólico , Aconitina/análise , Animais , Ácidos Araquidônicos , China , Cromatografia Líquida de Alta Pressão/métodos , Cicloparafinas , Medicamentos de Ervas Chinesas/química , Hiperplasia , Medicamentos sem Prescrição , Ácido Oleanólico/análise , Ratos , Triterpenos , Água
5.
Methods Mol Biol ; 2582: 209-221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370352

RESUMO

The remarkable regenerative capability of the liver has long been appreciated. Upon significant loss of liver tissue, the remnant liver can grow rapidly to restore the original liver mass through a combination of hepatocyte proliferation and hypertrophy to maintain homeostasis. Experimentally, 2/3 partial hepatectomy in mice has been used extensively as a model to dissect the molecular mechanism of liver regeneration and the genetic networks involved. Herein, we describe the protocols for partial hepatectomy and analyses of pertinent CCN protein functions.


Assuntos
Hepatectomia , Regeneração Hepática , Camundongos , Animais , Hepatectomia/métodos , Hepatócitos/metabolismo , Fígado/cirurgia , Hiperplasia , Proliferação de Células
6.
J Steroid Biochem Mol Biol ; 225: 106192, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167262

RESUMO

Diagnosis of nonclassic adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency (21-OHD) may be challenging due to its occult manifestations. To characterize clinical and molecular features of NCAH patients due to 21-hydroxylase deficiency, we retrospectively included 78 NCAH patients. Their phenotype and genotype were presented and compared. The transcription activities of novel CYP21A2 promoter variants were investigated using a dual-reporter luciferase assay system. This cohort included 53 females (68 %) and 25 males (32 %). The median of onset age was 13 years old (female: 13 range from 7 to 38; male: 11 range from 6 to 71). Menstrual cycle disorder was the most common complaint in females (62 %, n = 33) and for males, it was adrenal incidentalomas (52 %, n = 13). A total of 17 (22 %) patients complained of infertility. The most frequently variant was p.Ile173Asn (20 %, n = 31). Importantly, five variants in the promoter region including - 103/- 126 and - 196/- 296 were found in 21 (27 %) patients. Patients with promoter variants showed older onset age and less impaired hormone levels of 17-hydroxyprogesterone, ACTH, progesterone, and androstenedione. Compared with the wild-type promoter, the basic transcription activity of - 103/- 126 and - 196/- 296 promoter variants were reduced by 57% and 25%, respectively. Therefore, females with menstrual cycle disorders or infertility and males with adrenal incidentaloma should be considered of NCAH due to 21-OHD. When genotyping patients with NCAH, the promoter region of the CYP21A2 gene should be also investigated.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hiperplasia Suprarrenal Congênita , Infertilidade , Masculino , Feminino , Humanos , Neoplasias das Glândulas Suprarrenais/genética , Estudos Retrospectivos , Hiperplasia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Esteroide 21-Hidroxilase/genética
7.
Surg Clin North Am ; 103(1): 1-15, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36410343

RESUMO

Although the normal anatomy of the breast is relatively simple, a myriad of hyperplastic, atypical, and frankly malignant processes exist. Though a histologic continuum exists, the natural progression of breast disease is not always on a continuum. Moreover, the distinction between hyperplastic, atypical, and frankly malignant processes rests on subtle qualitative and sometimes quantitative features. The treatment of breast-related lesions has always been, and continues to be, a multidisciplinary task. A general understanding of histopathologic features of breast disease will allow clinicians to identify scenarios that are potentially inconsistent with the working diagnosis.


Assuntos
Doenças Mamárias , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Biomarcadores , Hiperplasia
8.
Horm Metab Res ; 54(2): 57-66, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35130566

RESUMO

To describe the differences in presentation, biochemistry, and radiological evaluation of various etiologies of adrenal Cushing's syndrome (CS) from a single center. To emphasize caution for interpretation of plasma adrenocorticotropic hormone (ACTH), as a spuriously unsuppressed ACTH level by immunometric assay may lead to therapeutic misadventures in adrenal CS. DESIGN: Retrospective, single-center, observational study. METHODS: Fifty-eight adrenal CS patients [Adrenocortical carcinoma (ACC), n=30; Adenoma (ACA), n=15; Primary pigmented nodular adrenocortical disease (PPNAD), n=10; ACTH independent macronodular adrenal hyperplasia (AIMAH), n=3) evaluated at a tertiary care center in western India between January 2006 to March 2020 were included. Data on demography, clinical evaluation, biochemistry, imaging, management, histopathology, and outcome were recorded in a standard format and analyzed. RESULTS: Cortisol secreting ACC presented at 38(1-50) years with abdominal mass in 26/30 (86.7%) and 16/30 (53.3%) had metastases at presentation. ACA with autonomous cortisol excess presented at 25(4.9-40) years with discriminating features of CS in 14/15 (93.3%), sex steroid production in 2/15, unenhanced HU <10 in only one, and relative washout >40% in 8/11 (72.7%). One ACA and eight ACC patients had plasma ACTH (by Siemens Immulite assay) > 20 pg/ml, despite hypercortisolemic state. CONCLUSIONS: Cortisol-secreting ACC and ACA most often present with mass effects and florid CS, respectively. Baseline HU has low sensitivity to differentiate cortisol-secreting ACA from ACC. Plasma ACTH measured by Seimens Immulite is often unsuppressed, especially in ACC patients, which can be addressed by measuring ACTH by more accurate assays.


Assuntos
Neoplasias do Córtex Suprarrenal , Síndrome de Cushing , Neoplasias do Córtex Suprarrenal/complicações , Hormônio Adrenocorticotrópico , Humanos , Hidrocortisona , Hiperplasia/complicações , Estudos Retrospectivos
9.
Anticancer Res ; 42(12): 5891-5895, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36456118

RESUMO

BACKGROUND/AIM: Nearly 70 years ago, Slaughter launched the hypothesis of field cancerization for oral carcinomas; that hypothesis was subsequently also claimed for carcinomas in other organs. We previously found in the colon mucosa adjacent to nonpolypoid adenomas, branching crypts lined by normal epithelium (BCNE). Here, we explored whether BCNE could also be found in the colon mucosa adjacent to sporadic polypoid tubular adenomas (TA), the most prevalent of all colon adenomas. PATIENTS AND METHODS: Nondysplastic mucosa adjacent to TA was found in 103 out of 131 TA. All BCNE adjacent to TA were recorded. RESULTS: In 98 (95.1%) out of 103 TA having nondysplastic adjacent mucosa, 645 BCNE were registered: 82.6% were in asymmetric branching and 17.4% in symmetric branching. Thus, BCNE in asymmetric branching predominated. The frequency of BCNE adjacent to TA was influenced by the adenoma size and degree of dysplasia severity. Contrarywise, the frequency of BCNE adjacent to TA was neither influenced by the age or sex of the patients, nor by the colon localization of TA. CONCLUSION: BCNE often occur in the normal mucosa adjacent to TA. BCNE emerge as integral components of TA. The majority of the BCNE were in asymmetric branching, considered as aberrations of cryptogenesis. We propose that the accretion of asymmetric BCNE adjacent to TA supports Slaughter's hypothesis of field cancerization.


Assuntos
Carcinoma , Neoplasias do Colo , Humanos , Epitélio , Hiperplasia
10.
Int Immunopharmacol ; 113(Pt A): 109392, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461594

RESUMO

BACKGROUND: One of the common pathophysiological basis of atherosclerosis is intimal hyperplasia. ATP citrate lyase (ACLY) has been reported as a promising therapeutic target for treatment of dyslipidemia and atherosclerosis. However, the role of ACLY in intimal hyperplasia has yet to be clarified. METHODS: The current investigation studies the molecular effects of ACLY and bempedoic acid, an ACLY inhibitor, on platelet-derived growth factor (PDGF)-induced primary human aortic smooth muscle cells (HASMCs) proliferation in vitro and on femoral arterial wire-injured neointimal hyperplasia in mouse in vivo. The role of ACLY in intimal hyperplasia was further investigated in mice treated with bempedoic acid. Cell proliferation was measured by CCK8 and BrdU assays. We explored further mechanisms using western blot, qPCR and immunofluorescence. RESULTS: We found that ACLY was significantly increased in dedifferentiated VSMC in vitro and vivo. Bempedoic acid which can inhibit ACLY expression effectively blocked PDGF-induced VSMC proliferation and dedifferentiation by activating AMPK/ACC signaling pathway. Moreover, bempedoic acid also attenuated VSMC proliferation and inhibited VSMC dedifferentiation in the wire-injured mouse femoral arteries, resulting in reduced neointima formation. CONCLUSIONS: We demonstrates that bempedoic acid reduces ACLY expression to restrain VSMC proliferation and dedifferentiation by activating AMPK/ACC signaling pathway, which may provide a potential therapeutic strategy for diseases associated with intimal hyperplasia including restenosis and atherosclerosis.


Assuntos
Proteínas Quinases Ativadas por AMP , Aterosclerose , Humanos , Camundongos , Animais , ATP Citrato (pro-S)-Liase , Hiperplasia/tratamento farmacológico , Inibidores Enzimáticos , Transdução de Sinais , Aciltransferases , Fator de Crescimento Derivado de Plaquetas
11.
Food Funct ; 13(23): 12077-12092, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36367287

RESUMO

Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathological process of neointima formation after vascular injury. Galangin, an extract of the ginger plant galangal, is involved in numerous biological activities, including inhibiting the proliferation and migration of tumor cells, but its effect on VSMCs is unknown. This study focused on the role and mechanism of galangin in the neointima formation induced by vascular injury. Methods and results: In this study, we found that galangin restrained the PDGF-BB-induced proliferation, migration and phenotypic switching of VSMCs in a concentration-dependent manner. In vivo, we established a model of carotid artery balloon injury in rats, followed by intragastric administration of galangin (40 mg kg-1 day-1 or 80 mg kg-1 day-1) for 14 or 28 consecutive days. Then, the degree of neointima hyperplasia was evaluated by H&E staining, and the level of relevant protein expression was assessed by immunofluorescence and western blotting. In vitro, we isolated and grew primary rat aortic smooth muscle cells, which were treated with PDGF-BB and different doses of galangin, and then CCK-8 assay, wound healing assay, transwell assay, western blotting and immunofluorescence assays were performed. We found that galangin significantly inhibited PDGF-BB-induced proliferation, migration, and phenotypic switching of VSMCs and promoted autophagy in VSMCs in vitro, and galangin significantly inhibited neointimal hyperplasia after the common carotid artery balloon injury in rats. In terms of mechanisms, galangin inhibited the PI3K/AKT/mTOR pathway, thereby suppressing VSMC's switch from a contractile to a synthetic phenotype, inhibiting VSMC proliferation, migration and phenotypic switching and upregulating the Beclin1 protein expression levels and the ratio of LC3BII/I, promoting VSMC autophagy, and thereby inhibiting neointimal hyperplasia after vascular injury. Conclusion: Our study suggests that galangin inhibits neointimal hyperplasia after vascular injury by inhibiting smooth muscle cell proliferation, migration and phenotypic switching and by promoting autophagy, and that galangin may be a promising drug for the prevention and treatment of vascular restenosis after PCI.


Assuntos
Lesões das Artérias Carótidas , Intervenção Coronária Percutânea , Lesões do Sistema Vascular , Ratos , Animais , Neointima/tratamento farmacológico , Neointima/metabolismo , Neointima/patologia , Becaplermina/metabolismo , Becaplermina/farmacologia , Becaplermina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Lesões do Sistema Vascular/tratamento farmacológico , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/metabolismo , Músculo Liso Vascular , Hiperplasia/metabolismo , Hiperplasia/patologia , Movimento Celular , Proliferação de Células , Ratos Sprague-Dawley , Lesões das Artérias Carótidas/tratamento farmacológico , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Miócitos de Músculo Liso , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Células Cultivadas
12.
Zhonghua Shao Shang Za Zhi ; 38(11): 1023-1033, 2022 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-36418259

RESUMO

Objective: The investigate the effects and mechanism of exosomes derived from human umbilical vein endothelial cells (HUVECs) on wound healing in diabetes rabbits. Methods: The experimental research methods were used. The primary vascular endothelial cells (VECs) and human skin fibroblasts (HSFs) were extracted from skin tissue around ulcer by surgical excision of two patients with diabetic ulcer (the male aged 49 years and the female aged 58 years) admitted to Xiangya Third Hospital of Central South University in June 2019. The cells were successfully identified through morphological observation and flow cytometry. The HUVEC exosomes were extracted by ultracentrifugation and identified successfully by morphological observation, particle size detection, and Western blotting detection. Twenty female 3-month-old New Zealand rabbits were taken to create one type 2 diabetic full-thickness skin defect wound respectively on both sides of the back. The wounds were divided into exosomes group and phosphate buffer solution (PBS) group and treated accordingly, with 20 wounds in each group, the time of complete tissue coverage of wound was recorded. On PID 14, hematoxylin-eosin staining or Masson staining was performed to observe angiogenesis or collagen fiber hyperplasia (n=20). The VECs and HSFs were co-cultured with HUVEC exosomes for 24 h to observe the uptake of HUVEC exosomes by the two kinds of cells. The VECs and HSFs were divided to exosome group treated with HUVEC exosomes and PBS group treated with PBS to detect the cell proliferation on 4 d of culture with cell count kit 8, to detect and calculate the cell migration rate at 24 and 48 h after scratch by scratch test, to detect the cell migration number at 24 h of culture with Transwell test, and to detect the mRNA expressions of nuclear factor-erythroid 2-related factor 2 (NRF2) and transcription activating factor 3 (ATF3) by real time fluorescence quantitative reverse transcription polymerase chain reaction. Besides, the number of vascular branches and vascular length were observed in the tube forming experiment after 12 h of culture of VECs (n=3). The VECs and HSFs were taken and divided into PBS group and exosome group treated as before, and NRF2 interference group, ATF3 interference group, and no-load interference group with corresponding gene interference. The proliferation and migration of the two kinds of cells, and angiogenesis of VECs were detected as before (n=3). Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and least significant difference test. Results: The time of complete tissue coverage of wound in exosome group was (17.9±1.9) d, which was significantly shorter than (25.2±2.3) d in PBS group (t=4.54, P<0.05). On PID14, the vascular density of wound in PBS group was significantly lower than that in exosome group (t=10.12, P<0.01), and the collagen fiber hyperplasia was less than that in exosome group. After 24 h of culture, HUVEC exosomes were successfully absorbed by VECs and HSFs. The proliferative activity of HSFs and VECs in exosome group was significantly higher than that in PBS group after 4 d of culture (with t values of 54.73 and 7.05, respectively, P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs (with t values of 3.42 and 11.87, respectively, P<0.05 or P<0.01) and VECs (with t values of 21.42 and 5.49, respectively, P<0.05 or P<0.01) in exosome group were significantly higher than those in PBS group. After 24 h of culture, the migration numbers of VECs and HSFs in exosome group were significantly higher than those in PBS group (with t values of 12.31 and 16.78, respectively, P<0.01). After 12 h of culture, the mRNA expressions of NRF2 in HSFs and VECs in exosome group were significantly higher than those in PBS group (with t values of 7.52 and 5.78, respectively, P<0.05 or P<0.01), and the mRNA expressions of ATF3 were significantly lower than those in PBS group (with t values of 13.44 and 8.99, respectively, P<0.01). After 12 h of culture, the number of vascular branches of VECs in exosome group was significantly more than that in PBS group (t=17.60, P<0.01), and the vascular length was significantly longer than that in PBS group (t=77.30, P<0.01). After 4 d of culture, the proliferation activity of HSFs and VECs in NRF2 interference group was significantly lower than that in PBS group and exosome group (P<0.05 or P<0.01); the proliferation activity of HSFs and VECs in ATF3 interference group was significantly higher than that in PBS group (P<0.05 or P<0.01) and significantly lower than that in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in ATF3 interference group were significantly higher than those in PBS group (P<0.05 or P<0.01) and significantly lower than those in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in NRF2 interference group were significantly lower than those in PBS group and exosome group (P<0.05 or P<0.01). After 24 h of culture, the migration numbers of VECs and HSFs in ATF3 interference group were significantly more than those in PBS group (P<0.05) and significantly less than those in exosome group (P<0.05 or P<0.01); the migration numbers of VECs and HSFs in NRF2 interference group were significantly less than those in PBS group and exosome group (P<0.01). After 12 h of culture, the vascular length and number of branches of VECs in NRF2 interference group were significantly decreased compared with those in PBS group and exosome group (P<0.01); the vascular length and number of branches of VECs in ATF3 interference group were significantly increased compared with those in PBS group (P<0.01) and were significantly decreased compared with those in exosome group (P<0.01). Conclusions: HUVEC exosomes can promote the wound healing of diabetic rabbits by promoting the proliferation and migration of VECs and HSFs, and NRF2 and ATF3 are obviously affected by exosomes in this process, which are the possible targets of exosome action.


Assuntos
Diabetes Mellitus , Exossomos , Animais , Feminino , Humanos , Masculino , Coelhos , Colágeno/metabolismo , Exossomos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Hiperplasia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , RNA Mensageiro/metabolismo , Úlcera , Cicatrização , Pessoa de Meia-Idade
13.
JAMA Netw Open ; 5(11): e2243951, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36441547

RESUMO

Importance: The association of tamoxifen use with the risk of uterine diseases, such as endometrial cancer, in premenopausal women with breast cancer remains controversial. However, many studies have reported an increased risk of uterine disease among postmenopausal tamoxifen users. Objective: To investigate the association of tamoxifen use with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer. Design, Setting, and Participants: A nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period was conducted using data obtained from the Korean National Health Insurance Service. Participants included premenopausal women aged 20 to 50 years with breast cancer diagnoses between January 2003 and December 2018. Data were analyzed from April to December 2021. Exposures: Tamoxifen treatment. Main Outcomes and Measures: The incidence of uterine diseases, including endometrial cancer, hyperplasia, polyps, and other uterine cancers, was identified in the study cohort using insurance claim codes. The incidence of uterine diseases per 1000 person-years was compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. Multivariable Cox proportional hazard regression analysis was performed to determine the risk of each uterine disease. Results: Among 78 320 female participants with a mean (SD) age of 42.1 (6.1) years, 34 637 (44.2%) were categorized into the tamoxifen group and 43 683 (55.8%) were categorized into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15) years, the incidence of newly diagnosed endometrial polyps was 20.13 cases per 1000 person-years, that of endometrial hyperplasia was 13.49 cases per 1000 person-years, that of endometrial cancer was 2.01 cases per 1000 person-years, and that of other uterine cancers was 0.45 cases per 1000 person-years. The risk of endometrial cancer was higher in the tamoxifen group than in the control group (hazard ratio, 3.77; 95% CI, 3.04-4.66) after adjusting for age, body mass index, history of diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, gonadotropin-releasing hormone agonist treatment, and trastuzumab treatment. Conclusions and Relevance: In this longitudinal cohort study, premenopausal Korean women with breast cancer who received tamoxifen as adjuvant hormone therapy had a significantly increased risk of endometrial hyperplasia, polyps, carcinoma, and other uterine cancers compared with those who were not treated with adjuvant hormone therapy. These findings suggest that clinicians should consider the risk of uterine disease among tamoxifen users, including premenopausal women.


Assuntos
Neoplasias da Mama , Carcinoma , Hiperplasia Endometrial , Neoplasias do Endométrio , Pólipos , Doenças Uterinas , Feminino , Humanos , Tamoxifeno/efeitos adversos , Hiperplasia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/epidemiologia , Estudos Retrospectivos , Estudos Longitudinais , Pólipos/induzido quimicamente , Pólipos/epidemiologia , Hormônios
14.
PLoS One ; 17(11): e0277423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36441728

RESUMO

Women and Black, Indigenous, and People of Color (BIPOC) employees are underrepresented in science and natural resource management institutions. Student and recent graduate trainee and internship programs have been used to try to address this in United States federal agencies over the last few decades. Our study evaluates how effective such programs are at improving U.S. federal workforce diversity. We used a comprehensive employee dataset from the United States Department of Agriculture (USDA) Forest Service-which has the largest natural resource management workforce in the country-to analyze the demographic characteristics and career paths of paid interns from 1996-2017. We found that a majority of employees who started as interns later converted to permanent employment with the USDA Forest Service. In addition, Black and Hispanic interns were, respectively, 5 and 3 times more likely than White interns to work for the agency in permanent positions after their internships. However, people who started as interns had significantly shorter USDA Forest Service careers than those who started in permanent positions. White women entering directly into permanent positions typically advanced to higher pay grades through promotion faster than White women who entered as interns. Finally, male BIPOC interns involuntarily separated (i.e., were fired) at significantly higher rates than all other employees. Our study suggests that while internship employment programs can be an effective tool for hiring a diverse workforce, they are not sufficient to close the overall workforce diversity gap. In addition, only a small percentage of new hires every year are interns. To achieve a level of representation that mirrors the civilian labor force, our study suggests that internship programs need to focus on long-term employee retention and be of significantly larger scale.


Assuntos
Internato e Residência , Estados Unidos , Feminino , Masculino , Humanos , United States Department of Agriculture , Salários e Benefícios , Capacitação em Serviço , Estudantes , Excipientes , Hiperplasia
15.
Schweiz Arch Tierheilkd ; 164(11): 801-804, 2022 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-36325643

RESUMO

INTRODUCTION: Reports on bovine colon polyps are rare. The present report demonstrates macro- and microscopically hyperplastic colon polyps of a seven-year-old German Simmental cow. Differential diagnoses (adenoma and adenocarcinoma) and aetiology are discussed. Even in cattle, intestinal polyps should be considered as a cause of intussusception.


INTRODUCTION: Les rapports concernant des polypes du colon chez les bovins sont rares. Le présent rapport fait état de polypes du côlon macro- et microscopiquement hyperplasiques chez une vache Simmental allemande de sept ans. Les diagnostics différentiels (adénome et adénocarcinome) et l'étiologie sont discutés. Même chez les bovins, les polypes intestinaux doivent être considérés comme une cause d'invagination.


Assuntos
Adenocarcinoma , Adenoma , Doenças dos Bovinos , Pólipos do Colo , Bovinos , Animais , Pólipos do Colo/diagnóstico , Pólipos do Colo/veterinária , Pólipos do Colo/patologia , Hiperplasia/veterinária , Hiperplasia/patologia , Adenoma/diagnóstico , Adenoma/veterinária , Adenoma/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/veterinária , Adenocarcinoma/patologia , Colo/patologia , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/patologia
16.
BMJ Case Rep ; 15(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357100

RESUMO

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare but important condition to consider when investigating a patient with suspected thoracic malignancy. There is very little known about DIPNECH and it is considered to be a precursor to carcinoid tumour of the lung. This case report aims to increase awareness of this largely unknown and rare condition and to better improve its consideration as a differential diagnosis in patients who remain unresponsive to conventional treatment.


Assuntos
Tumor Carcinoide , Pneumopatias , Neoplasias Pulmonares , Células Neuroendócrinas , Humanos , Células Neuroendócrinas/patologia , Hiperplasia/patologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/etiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem
18.
Obstet Gynecol ; 140(6): 1061-1075, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36357974

RESUMO

The objectives of this Clinical Expert Series on endometrial hyperplasia are to review the etiology and risk factors, histologic classification and subtypes, malignant progression risks, prevention options, and to outline both surgical and nonsurgical treatment options. Abnormal uterine and postmenopausal bleeding remain the hallmark of endometrial pathology, and up to 10-20% of postmenopausal bleeding will be either hyperplasia or cancer; thus, immediate evaluation of any abnormal bleeding with either tissue procurement for pathology or imaging should be undertaken. Although anyone with a uterus may develop atypical hyperplasia, also known as endometrial intraepithelial neoplasia (EIN), genetic predispositions (eg, Lynch syndrome), obesity, chronic anovulation, and polycystic ovarian syndrome all markedly increase these risks, whereas use of oral contraceptive pills or progesterone-containing intrauterine devices will decrease the risk. An EIN diagnosis carries a high risk of concomitant endometrial cancer or eventual progression to cancer in the absence of treatment. The definitive and curative treatment for EIN remains hysterectomy; however, the obesity epidemic, the potential desire for fertility-sparing treatments, the recognition of varying rates of malignant transformation, medical comorbidities, and an aging population all may factor into decisions to employ nonsurgical treatment modalities.


Assuntos
Carcinoma in Situ , Hiperplasia Endometrial , Neoplasias do Endométrio , Idoso , Feminino , Humanos , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/etiologia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Hiperplasia/complicações , Obesidade/complicações , Obesidade/epidemiologia , Hemorragia Uterina/etiologia
19.
Asian Pac J Cancer Prev ; 23(11): 3915-3922, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36444605

RESUMO

AIM: The aim of this study was to evaluate the expression of human papillomavirus (HPV) in oral potentially malignant disorders (OPMD) and to examine the association of HPV in histological grades of dysplasia using p16 and Anti-E6 oncoprotein immunohistochemistry (IHC). SUBJECTS AND METHODS: This study focused on clinically diagnosed oral potentially malignant disorders. Clinical parameters such as age, gender, habits, occupation, duration, site, and the type of the lesions were examined and the incisional biopsy was done on the selected cases for the histopathological diagnosis. Selected cases of OPMDs were screened immunohistochemically for HPV 16 and HPV 18 (high-risk group) positivity using p16INK4a and Anti-E6 oncoprotein. The immunohistochemical p16 expression was evaluated based on (a) percentage of p16 positive cases and (b) pattern of p16 staining in various grades of OPMD. RESULTS: Anti-E6 oncoprotein (HR-HPV) expression level was only detected in 11 cases (37%), and positive expression of p16 was found in three cases (10%), with variation in cell proportion and intensity. Subsequently, the association between p16 expression level and clinicopathological characteristic factors was analyzed and a significant association was found between age and histopathology. CONCLUSION: There was an association between HPV and OPMD. Both biomarker tests, HPV E6 and p16 immunocytochemistry had a specific role in the detection of HR-HPV. Anti-E6 immunocytochemistry can be a valuable test with higher specificity for HPV DNA detection in oral epithelial dysplasia without losing sensitivity.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Inibidor p16 de Quinase Dependente de Ciclina , Hiperplasia , Proteínas Oncogênicas
20.
Pathol Res Pract ; 240: 154214, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36395596

RESUMO

In sessile serrated lesions (SSLs) with adenomatous dysplasia, the dysplastic component and the serrated component without dysplasia should be considered as part of the same lesion, classified as SSL with dysplasia. However, some of these lesions may actually represent collisions between a serrated polyp and a conventional adenoma. Further supporting the "collision theory", conventional adenomatous dysplasia may be found in association with hyperplastic polyps (HPs). In order to determine the molecular and biological landscape of conventional type dysplasia in serrated lesions, we collected 17 cases of colorectal serrated lesions with adenomatous dysplasia, classifying them as SSL with dysplasia (n = 10) or as mixed lesions comprising a HP component and a conventional adenomatous component (n = 7). We characterized the dysplastic and the non-dysplastic component of each lesion, after microdissection, through the targeted mutational analysis of 11 commonly altered genes in colorectal cancer (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53). We also characterized MMR and p53 status by immunohistochemistry. Overall, 14/17 (82.4 %) cases harbored a mutation in at least one of the two components. The most altered genes were BRAF in 10/17 (58.8 %) cases, APC in 2/17 (11.8 %) and TP53 in 4/17 (23.5 %). Among the SSL with dysplasia, the mutational profile was concordant between the two components in 7/10 (70 %) cases, while among the mixed lesions, the mutational profile was concordant in 1/7 (14.3 %). In all but two cases of SSL with dysplasia, MMR status was concordant between the two components of the serrated lesions. Our findings suggest that adenomatous dysplasia may develop in SSL as part of the serrated lesion, even if some SSL with dysplasia may actually be collision lesions. On the other hand, the polyps that are morphologically classifiable as mixed lesions composed of a HP and a conventional adenomatous component are more likely to be collision lesions.


Assuntos
Neoplasias Colorretais , Pólipos , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Hiperplasia , Mutação , Neoplasias Colorretais/genética
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