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1.
Biomaterials ; 313: 122767, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39216327

RESUMO

Peripheral artery disease is commonly treated with balloon angioplasty, a procedure involving minimally invasive, transluminal insertion of a catheter to the site of stenosis, where a balloon is inflated to open the blockage, restoring blood flow. However, peripheral angioplasty has a high rate of restenosis, limiting long-term patency. Therefore, angioplasty is sometimes paired with delivery of cytotoxic drugs like paclitaxel to reduce neointimal tissue formation. We pursue intravascular drug delivery strategies that target the underlying cause of restenosis - intimal hyperplasia resulting from stress-induced vascular smooth muscle cell switching from the healthy contractile into a pathological synthetic phenotype. We have established MAPKAP kinase 2 (MK2) as a driver of this phenotype switch and seek to establish convective and contact transfer (coated balloon) methods for MK2 inhibitory peptide delivery to sites of angioplasty. Using a flow loop bioreactor, we showed MK2 inhibition in ex vivo arteries suppresses smooth muscle cell phenotype switching while preserving vessel contractility. A rat carotid artery balloon injury model demonstrated inhibition of intimal hyperplasia following MK2i coated balloon treatment in vivo. These studies establish both convective and drug coated balloon strategies as promising approaches for intravascular delivery of MK2 inhibitory formulations to improve efficacy of balloon angioplasty.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Serina-Treonina Quinases , Ratos Sprague-Dawley , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Peptídeos/química , Peptídeos/farmacologia , Ratos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/citologia , Angioplastia com Balão/métodos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Sistemas de Liberação de Medicamentos , Hiperplasia/prevenção & controle , Angioplastia , Neointima/prevenção & controle , Neointima/patologia
2.
J Vis Exp ; (210)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39221950

RESUMO

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement. Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy. One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.


Assuntos
Lobo Frontal , Malformações do Desenvolvimento Cortical , Humanos , Lobo Frontal/cirurgia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Malformações do Desenvolvimento Cortical/cirurgia , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/patologia , Masculino , Feminino , Pré-Escolar , Criança , Epilepsia/cirurgia , Epilepsia/diagnóstico por imagem , Epilepsia/etiologia , Oligodendroglia/patologia , Lactente , Estudos Retrospectivos , Epilepsia do Lobo Frontal/cirurgia , Epilepsia do Lobo Frontal/diagnóstico por imagem , Epilepsia do Lobo Frontal/patologia , Hiperplasia/cirurgia
4.
J Zoo Wildl Med ; 55(3): 838-842, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39255229

RESUMO

Gastric and intestinal mucosal hyperplasia and polyps are identified as a cause of morbidity and mortality in moray eels. This report describes the clinical presentations, diagnostic procedures, and therapeutic interventions in eight moray eels diagnosed with gastric polypoid hyperplasia. All described cases were humanely euthanized or found deceased, and multifocal adenomatous hyperplasia and polyps extending from the gastric mucosal epithelium were identified in all cases. The moray eels diagnosed with adenomatous hyperplasia and polyps often exhibited anorexia, regurgitation, and occasional changes in buoyancy, and supportive care was unsuccessful in alleviating or resolving these signs.


Assuntos
Enguias , Hiperplasia , Animais , Hiperplasia/veterinária , Hiperplasia/patologia , Feminino , Masculino , Doenças dos Peixes/patologia , Doenças dos Peixes/diagnóstico , Pólipos/veterinária , Pólipos/patologia , Pólipos/diagnóstico , Gastropatias/veterinária , Gastropatias/patologia , Gastropatias/diagnóstico
5.
Nat Cardiovasc Res ; 3(5): 541-557, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39195932

RESUMO

Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell-cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts.


Assuntos
Artéria Torácica Interna , Animais , Humanos , Artéria Torácica Interna/transplante , Artéria Torácica Interna/metabolismo , Análise de Célula Única , Artéria Radial/transplante , Artéria Radial/metabolismo , Artéria Gastroepiploica/metabolismo , Artéria Gastroepiploica/transplante , Miócitos de Músculo Liso/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neointima/patologia , Neointima/metabolismo , Ponte de Artéria Coronária/métodos , Comunicação Celular , Fibroblastos/metabolismo , Células Endoteliais/metabolismo , Camundongos , Transdução de Sinais , Transcriptoma , Vasoconstrição/efeitos dos fármacos , Células Cultivadas , Hiperplasia/metabolismo , Hiperplasia/patologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
6.
Nat Commun ; 15(1): 7398, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191789

RESUMO

Smooth muscle cell (SMC) phenotypic modulation, primarily driven by PDGFRß signaling, is implicated in occlusive cardiovascular diseases. However, the promotive and restrictive regulation mechanism of PDGFRß and the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14) in neointimal hyperplasia remain unclear. Our study observes a marked upregulation of PTPN14 in SMCs during neointimal hyperplasia. PTPN14 overexpression exacerbates neointimal hyperplasia in a phosphatase activity-dependent manner, while SMC-specific deficiency of PTPN14 mitigates this process in mice. RNA-seq indicates that PTPN14 deficiency inhibits PDGFRß signaling-induced SMC phenotypic modulation. Moreover, PTPN14 interacts with intracellular region of PDGFRß and mediates its dephosphorylation on Y692 site. Phosphorylation of PDGFRßY692 negatively regulates PDGFRß signaling activation. The levels of both PTPN14 and phospho-PDGFRßY692 are correlated with the degree of stenosis in human coronary arteries. Our findings suggest that PTPN14 serves as a critical modulator of SMCs, promoting neointimal hyperplasia. PDGFRßY692, dephosphorylated by PTPN14, acts as a self-inhibitory site for controlling PDGFRß activation.


Assuntos
Hiperplasia , Miócitos de Músculo Liso , Neointima , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Transdução de Sinais , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Animais , Hiperplasia/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Humanos , Neointima/metabolismo , Neointima/patologia , Camundongos , Fosforilação , Masculino , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vasos Coronários/patologia , Vasos Coronários/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia
7.
Ulus Travma Acil Cerrahi Derg ; 30(8): 525-530, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39092970

RESUMO

BACKGROUND: Intimal hyperplasia is a normal adaptive feature of arteries in response to injuries, which include invasive vascular interventions. Its development limits the long-term success of bypass grafts. Various pharmacological agents have been successfully employed in experimental models to reduce the degree of intimal hyperplasia. In our study, we investigated the efficacy of dexamethasone in reducing intimal hyperplasia in rat abdominal aortas after partial transection and primary repair. METHODS: In this study, 20 Wistar Albino rats were randomly selected and divided into four groups to compare the effects of low- and high-dose dexamethasone on intima and media thickness compared to the control. Group A (n=5) was the control group, where only skin incision and laparotomy were performed. For Group B (n=5), a median laparotomy was performed, the abdominal aorta was partially transected, and repaired with an 8.0 prolene suture. Doses of 0.1 mg/kg and 0.2 mg/kg dexamethasone were administered in Group C (n=5) and Group D (n=5), respectively. After two weeks, all rats were euthanized, and the repaired abdominal aortas were excised and examined histopathologically. Intima and media thicknesses were measured using the 'Olympus AnalySIS 5' program (Olympus Corporation, Japan) after digital photos were taken. RESULTS: Based on the measurements, we demonstrated that after transection and repair of the abdominal aorta, the intima/media ratio was not significantly different between the low-dose dexamethasone and non-dexamethasone groups. The intima/media ratio was significantly lower in the high-dose dexamethasone group than in the non-dexamethasone and low-dose dexamethasone groups. CONCLUSION: After vascular interventions, dexamethasone treatment may reduce intimal hyperplasia and increase patency by providing vascular remodeling.


Assuntos
Aorta Abdominal , Dexametasona , Hiperplasia , Ratos Wistar , Túnica Íntima , Animais , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Aorta Abdominal/cirurgia , Aorta Abdominal/patologia , Ratos , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Hiperplasia/prevenção & controle , Túnica Íntima/patologia , Túnica Íntima/efeitos dos fármacos , Modelos Animais de Doenças , Masculino
8.
J Physiol ; 602(17): 4291-4307, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39106251

RESUMO

ClC-K/barttin channels are involved in the transepithelial transport of chloride in the kidney and inner ear. Their physiological role is crucial in humans because mutations in CLCNKB or BSND, encoding ClC-Kb and barttin, cause Bartter's syndrome types III and IV, respectively. In vitro experiments have shown that an amino acid change in a proline-tyrosine motif in the C-terminus of barttin stimulates ClC-K currents. The molecular mechanism of this enhancement and whether this potentiation has any in vivo relevance remains unknown. We performed electrophysiological and biochemical experiments in Xenopus oocytes and kidney cells co-expressing ClC-K and barttin constructs. We demonstrated that barttin possesses a YxxØ motif and, when mutated, increases ClC-K plasma membrane stability, resulting in larger currents. To address the impact of mutating this motif in kidney physiology, we generated a knock-in mouse. Comparing wild-type (WT) and knock-in mice under a standard diet, we could not observe any difference in ClC-K and barttin protein levels or localization, either in urinary or plasma parameters. However, under a high-sodium low-potassium diet, known to induce hyperplasia of distal convoluted tubules, knock-in mice exhibit reduced hyperplasia compared to WT mice. In summary, our in vitro and in vivo studies demonstrate that the previously identified PY motif is indeed an endocytic YxxØ motif in which mutations cause a gain of function of the channel. KEY POINTS: It is revealed by mutagenesis and functional experiments that a previously identified proline-tyrosine motif regulating ClC-K plasma membrane levels is indeed an endocytic YxxØ motif. Biochemical characterization of mutants in the YxxØ motif in Xenopus oocytes and human embryonic kidney cells indicates that mutants showed increased plasma membrane levels as a result of an increased stability, resulting in higher function of ClC-K channels. Mutation of this motif does not affect barttin protein expression and subcellular localization in vivo. Knock-in mice with a mutation in this motif, under conditions of a high-sodium low-potassium diet, exhibit less hyperplasia in the distal convoluted tubule than wild-type animals, indicating a gain of function of the channel in vivo.


Assuntos
Canais de Cloreto , Endocitose , Xenopus laevis , Animais , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Endocitose/fisiologia , Camundongos , Túbulos Renais Distais/metabolismo , Hiperplasia , Humanos , Feminino , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo , Camundongos Endogâmicos C57BL , Células HEK293 , Oócitos/metabolismo , Proteínas de Transporte de Ânions
9.
Radiologia (Engl Ed) ; 66(4): 381-385, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39089798

RESUMO

Papillary endothelial hyperplasia (PEH) or Masson's tumor is a rare benign vascular tumor that usually appears in the soft tissues of the head and neck, trunk and extremities, being extremely rare in the breast. Its diagnosis can be a challenge, especially in the follow-up of patients with previous disease of breast carcinoma. We present the case of a 65-year-old patient, with a history of bilateral breast cancer and reconstruction with implants, who presented a Masson's tumor during follow-up. An ultrasound scan was performed, showing a well-circumscribed mass in the left breast, located in the posterior contour of the implant. Subsequently, magnetic resonance imaging (MR) depicted an enhancing tumor, without infiltration of adjacent structures. Finally, the definitive anatomopathological diagnosis was obtained after surgical excision.


Assuntos
Doenças Mamárias , Neoplasias da Mama , Hiperplasia , Humanos , Idoso , Feminino , Hiperplasia/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/patologia , Imageamento por Ressonância Magnética
11.
Nat Cardiovasc Res ; 3(9): 1140-1157, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39198628

RESUMO

Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.


Assuntos
Animais Recém-Nascidos , Ventrículos do Coração , Ramos Subendocárdicos , Regeneração , Animais , Regeneração/fisiologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Ramos Subendocárdicos/fisiopatologia , Ramos Subendocárdicos/fisiologia , Ramos Subendocárdicos/patologia , Proliferação de Células , Hiperplasia/patologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/fisiologia , Linhagem da Célula , Camundongos , Camundongos Transgênicos
12.
Artigo em Chinês | MEDLINE | ID: mdl-39193744

RESUMO

Objective:To investigate the long-term effect of partial tonsillectomy in children with tonsil hypertrophy. Methods:A total of 146 children with obstructive sleep apnea(OSA) who received surgical treatment for tonsil hyperplasia from January 2010 to January 2013 were selected and divided into the observation group(n=69) and the control group(n=77). The observation group was received tonsillotomy(TT), and the control group was received total tonsillectomy(TE). Parental satisfaction and OSA quality of life questionnaire for children(OSA-18) were surveyed. Residual tonsil size was measured, and polysomnography(PSG) was monitored after 10 years. HE and immunohistochemical analysis were performed on tonsil tissues of one patient who performed a second operation after TT in 2017 year. Results:The results of questionnaire survey showed that the symptoms of respiratory obstruction were significantly improved in both groups, and the satisfaction of TT group was higher than that in the TE group. No increase in the number of respiratory tract infections was observed in all patients. In the TT group, nine cases(13.04%) had tonsil hyperplasia toⅡ°, and the remaining patients had tonsil hyperplasia to Ⅰ°. In addition, one case hadtonsil suppurative infection at the 14th month after surgery, and no recurrence or reoperation was found after treatment. There were seven cases in the TT group and eight cases in the TE group with occasional snoring and mouth breathing after surgery, but the PSG examination of the patients did not meet the diagnosis of OSA. The main causes were obesity and allergic rhinitis. Compared with the first operation, the cicatricial obstruction and infection of tonsil tissue in the second operation were not significantly changed, and the immunohistochemical results also demonstrated that the expression of CD20 was not changed, and the expression of CD3 was decreased. Conclusion:Both TT and TE can effectively improve the symptoms of OSA obstruction in children. TT has less trauma, less postoperative pain, faster recovery and lower rate of hyperplasia, which can be used as one of the main methods for the treatment of tonsil hypertrophy in children.


Assuntos
Hiperplasia , Hipertrofia , Tonsila Palatina , Apneia Obstrutiva do Sono , Tonsilectomia , Humanos , Tonsilectomia/métodos , Apneia Obstrutiva do Sono/cirurgia , Criança , Masculino , Feminino , Hiperplasia/cirurgia , Tonsila Palatina/cirurgia , Tonsila Palatina/patologia , Hipertrofia/cirurgia , Resultado do Tratamento , Qualidade de Vida , Inquéritos e Questionários , Polissonografia , Pré-Escolar , Satisfação do Paciente , Reoperação
13.
BMC Womens Health ; 24(1): 460, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160498

RESUMO

BACKGROUND: We conducted this study to clarify the magnetic resonance imaging (MRI) characteristics of lobular endocervical glandular hyperplasia (LEGH) and Nabothian cysts. METHODS: This study included 48 patients who underwent hysterectomy at our institution between 2016 and 2020 for suspected LEGH. Histopathological studies confirmed the presence of 25 Nabothian cysts and 23 cases of LEGH. We retrospectively analyzed five characteristic MRI findings: (1) located at the upper cervical canal, (2) positioned within the cervical stroma, (3) not circumscribing the cervical canal, (4) low- to iso-intensity on T1-weighted images (T1WI), and (5) "cosmos" or "microcystic" pattern. We compared the diagnostic accuracy of these findings for LEGH and Nabothian cysts using sensitivity, specificity, and predictive values. Combinations of findings were also calculated. RESULTS: The characteristics "cosmos" or "microcystic" pattern, lesion not circumscribing the cervical canal, and low/iso-intensity on T1WI had a sensitivity and specificity greater than 50%. The sensitivity was 73.9% and specificity 84.0% when a combination of "cosmos" or "microcystic" pattern and lesion not circumscribing the cervical canal was present. CONCLUSION: The coexistence of a "cosmos" or "microcystic" pattern and not circumscribing the cervical canal was the most characteristic finding that distinguished LEGH from Nabothian cysts. When neither of these findings is present, Nabothian cyst can be suspected.


Assuntos
Colo do Útero , Cistos , Imageamento por Ressonância Magnética , Sensibilidade e Especificidade , Humanos , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Cistos/diagnóstico por imagem , Cistos/diagnóstico , Cistos/patologia , Adulto , Colo do Útero/patologia , Colo do Útero/diagnóstico por imagem , Idoso , Hiperplasia/diagnóstico por imagem , Hiperplasia/diagnóstico , Hiperplasia/patologia , Histerectomia , Doenças do Colo do Útero/diagnóstico , Doenças do Colo do Útero/diagnóstico por imagem , Doenças do Colo do Útero/patologia , Cuidados Pré-Operatórios/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
14.
World J Gastroenterol ; 30(27): 3336-3355, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39086748

RESUMO

BACKGROUND: Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. AIM: To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. METHODS: Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. RESULTS: Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. CONCLUSION: This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Pólipos do Colo/microbiologia , Pólipos do Colo/patologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , RNA Ribossômico 16S/genética , Idoso , Fezes/microbiologia , Tailândia/epidemiologia , Adulto , Adenoma/microbiologia , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Hiperplasia/microbiologia , Estudos de Casos e Controles , Disbiose/microbiologia , População do Sudeste Asiático
15.
Clin Respir J ; 18(8): e13827, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39138819

RESUMO

In the two decades that have elapsed since the initial proposal of neuroendocrine cell hyperplasia of infancy (NEHI), several hundred cases have been reported and researched. However, a comprehensive analysis of research progress remains absent from the literature. The present article endeavors to evaluate the current progress of NEHI research and offer a reference for the clinical management of this condition.


Assuntos
Hiperplasia , Células Neuroendócrinas , Humanos , Células Neuroendócrinas/patologia , Hiperplasia/patologia , Lactente , Masculino , Feminino
16.
Asian Pac J Cancer Prev ; 25(7): 2567-2571, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39068592

RESUMO

BACKGROUND AND AIM: Colorectal cancer (CRC) is considered one of the most common cancers in the world. Serrated polyps were found to be precursor lesions for CRC. BRAF mutation (V600E) has been strongly linked to the development of these lesions. No previous study concerning BRAF immunohistochemical expression in serrated polyps- was done in Oman. The primary objective of our study was to assess the prevalence of BRAF (V600E) mutation in serrated colorectal polyps in the Omani population. The secondary objectives were to assess the prevalence of serrated polyps and their characteristic features: type, site and size as well as the relationship between BRAF (V600E) mutation and polyp type, site and size. MATERIALS AND METHODS: Ninety-one hyperplastic polyps (HP) (76.5%), 24 sessile serrated lesions (SSL) (20.2%) and 4 cases of tubular adenomas with low grade dysplasia (3.4%) were studied for BRAF (V600E) immunohistochemical expression. No case of traditional serrated adenoma (TSA) was present. Control cases of craniopharyngioma and papillary thyroid carcinoma were included. RESULTS: BRAF (V600E) IHC was positive in 63 of the HP polyps (69.2%), 13 SSLs (54.2%) and none of the adenomatous polyps. The majority of positive polyps (75.0%) were ≤5 mm in size, 17.9% were 5-10 mm and 7.1% were ≥10 mm in size.  The majority of BRAF (V600E) positive polyps (68.1 %) were in the distal colon and 31.9 % were in the proximal colon. The majority of positive cases for BRAF (V600E) were showing multiple polyps (61.8 %). None of the tubular adenomas showed any BRAF (V600E) positivity. CONCLUSION: Serrated polyps are now well known for their potential to develop CRC. Immunohistochemistry is an easy and reproducible way to detect BRAF (V600E) mutation. Our study showed there is high prevalence (64.3%) of BRAF mutation in serrated polyps in the Omani population. The majority of these polyps- were HP and SSL; and ≤5 mm in size and located in the distal colon.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Mutação , Proteínas Proto-Oncogênicas B-raf , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Feminino , Masculino , Omã , Pólipos do Colo/genética , Pólipos do Colo/patologia , Pólipos do Colo/metabolismo , Pessoa de Meia-Idade , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Adulto , Adenoma/genética , Adenoma/patologia , Adenoma/metabolismo , Centros de Atenção Terciária , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Idoso , Seguimentos , Estudos de Casos e Controles , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/metabolismo , Adulto Jovem , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Técnicas Imunoenzimáticas , Hiperplasia/genética , Hiperplasia/patologia , Hiperplasia/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Carcinoma Papilar/metabolismo
17.
Int J Pharm ; 662: 124500, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39033944

RESUMO

Hyperplasia of mammary glands (HMG) is considered a precancerous condition with a risk of malignant transformation, highlighting the necessity of proactive treatment in the early stages. Transdermal drug delivery offers significant advantages such as painlessness, absence of first-pass effect, and good patient compliance. However, the unique structure of the breast requires transdermal formulations for treating mammary hyperplasia to exhibit higher levels of safety and comfort. We have formulated an ancient topical formula called 'Muxiang Bing,' comprising traditional Chinese medicines Aucklandiae Radix (AR) and Rehmanniae Radix (RR), for the treatment of HMG. This formula has been transformed into a gel paster in the form of nipple cover for trans-nipple-areola delivery. In our investigations, we observed that the optimal formulation of the Muxiang gel plaster demonstrated enhanced permeation facilitated by AR's effect on RR. Furthermore, pre-treatment with the Muxiang gel plaster improved mammary tissue morphology, hormone levels, oxidative stress, aberrant cell proliferation, and damage in rat models, thus preventing and ameliorating mammary hyperplasia. The Muxiang gel plaster exhibited low skin irritability in rats, and long-term use did not cause harm to their internal organs or blood cells, indicating its safety and efficacy.


Assuntos
Administração Cutânea , Medicamentos de Ervas Chinesas , Géis , Hiperplasia , Mamilos , Ratos Sprague-Dawley , Animais , Feminino , Mamilos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Ratos , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Absorção Cutânea , Doenças Mamárias/tratamento farmacológico
18.
Int Orthod ; 22(3): 100896, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38981305

RESUMO

A satisfactory treatment of an 18-year-old lady was reported with right combination-type condylar hyperplasia (CH) in active phase. The chin severely deviated to the left, with the right gonial angle locating at a lower level. Intraorally, the lower centre line shifted to the left, the scale of which reached the width of one lower incisor. The right molar relation was mesial. Right maxillary second molar over-erupted without contact to lower teeth. There had been 2.5-mm anterior open bite (AOB) before surgery (T1) due to the tongue-spitting habit. After judging the benefits and disadvantages of all treatment alternatives, the decision was made to perform a right condylectomy and post-surgery orthodontics. Before orthodontics (T2) when the chin was positioned centred, an asymmetrical open bite occurred, caused by pre-contact between the right maxillary and mandibular second molars. Meanwhile, the AOB at T2 became 11.5mm. Orthodontic-related treatment included four premolars extraction and intrusion of bilateral maxillary molars using four miniscrews. Finally, this treatment achieved a clinically centred chin with two gonial angles at the same level. Post-condylectomy, the large AOB was resolved, together with a bilateral neutral molar relationship and alignment of the incisor midlines. Besides, the resected right condyle was covered by a continuous cortex bone and returned to the glenoid fossa. In sum, a high-challenging combined-type CH case was accomplished with impressive improvement in facial and occlusal symmetry, thanks to condylectomy and post-surgery miniscrew-assisted orthodontics.


Assuntos
Cefalometria , Hiperplasia , Côndilo Mandibular , Mordida Aberta , Humanos , Feminino , Adolescente , Mordida Aberta/terapia , Mordida Aberta/cirurgia , Côndilo Mandibular/cirurgia , Côndilo Mandibular/patologia , Ortodontia Corretiva/métodos , Assimetria Facial/cirurgia , Assimetria Facial/etiologia , Planejamento de Assistência ao Paciente , Procedimentos Cirúrgicos Ortognáticos/métodos
19.
Animal Model Exp Med ; 7(4): 397-407, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38970173

RESUMO

BACKGROUND: Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health. Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis. Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypotensive effect. This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L. (CuECs) and cucurbitacin B (CuB) on restenosis. METHODS: C57BL/6 mice were subjected to left carotid artery ligation and subcutaneously injected with CuECs or CuB for 4 weeks. Hematoxylin-Eosin, immunofluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia. Western blot, real-time PCR, flow cytometry analysis, EdU staining and cellular immunofluorescence assay were employed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro. The potential interactions of CuECs with cyclin A2 were performed by molecular docking. RESULTS: The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells. Furthermore, CuECs and CuB mediated cell cycle arrest at the S phase. Autodocking analysis demonstrated that CuB, CuD, CuE and CuI had high binding energy for cyclin A2. Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression. Moreover, the expression of cyclin A2 in CuEC- and CuB-treated neointima was downregulated. CONCLUSIONS: CuECs, especially CuB, exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.


Assuntos
Proliferação de Células , Ciclina A2 , Hiperplasia , Camundongos Endogâmicos C57BL , Músculo Liso Vascular , Neointima , Animais , Proliferação de Células/efeitos dos fármacos , Neointima/tratamento farmacológico , Neointima/patologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Ciclina A2/metabolismo , Hiperplasia/tratamento farmacológico , Hiperplasia/prevenção & controle , Masculino , Camundongos , Cucurbitacinas/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos
20.
Semin Diagn Pathol ; 41(5): 243-249, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39084918

RESUMO

Several neoplastic and non-neoplastic proliferations of the appendix can show varying degrees of serrated epithelial architecture. Of these, diffuse mucosal hyperplasia is most common, followed in frequency by low-grade mucinous and serrated neoplasms. It is important to distinguish serrated appendiceal neoplasms from their potential mimics because these entities may be managed differently. Diffuse mucosal hyperplasia is a non-neoplastic change that usually develops in the setting of resolving appendicitis and requires no further therapy or surveillance, and serrated neoplasms confined to the mucosa are adequately treated by appendectomy alone. On the other hand, low-grade appendiceal mucinous neoplasms may require surveillance, and those with extra-appendiceal spread differ from adenocarcinomas arising from serrated neoplasms with respect to both treatment and prognosis. Low-grade mucinous neoplasms in the peritoneum are frequently amenable to peritoneum-directed therapies alone, while adenocarcinomas derived from serrated neoplasms often spread to both regional lymph nodes and the peritoneum, potentially requiring right colectomy and systemic chemotherapy. The purpose of this review is to summarize the literature regarding the clinical and pathologic features of appendiceal lesions that show epithelial serration and provide the reader with helpful tips to distinguish serrated neoplasms from their mimics.


Assuntos
Neoplasias do Apêndice , Humanos , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Diagnóstico Diferencial , Hiperplasia/patologia , Apêndice/patologia
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