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1.
Proc Natl Acad Sci U S A ; 121(17): e2322363121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38640341

RESUMO

Anti-microbial resistance (AMR) is one of the greatest threats to global health. The continual battle between the emergence of AMR and the development of drugs will be extremely difficult to stop as long as traditional anti-biotic approaches are taken. In order to overcome this impasse, we here focused on the type III secretion system (T3SS), which is highly conserved in many Gram-negative pathogenic bacteria. The T3SS is known to be indispensable in establishing disease processes but not essential for pathogen survival. Therefore, T3SS inhibitors may be innovative anti-infective agents that could dramatically reduce the evolutionary selective pressure on strains resistant to treatment. Based on this concept, we previously identified a polyketide natural product, aurodox (AD), as a specific T3SS inhibitor using our original screening system. However, despite its promise as a unique anti-infective drug of AD, the molecular target of AD has remained unclear. In this paper, using an innovative chemistry and genetic biology-based approach, we show that AD binds to adenylosuccinate synthase (PurA), which suppresses the production of the secreted proteins from T3SS, resulting in the expression of bacterial virulence both in vitro and in vivo experiments. Our findings illuminate the potential of PurA as a target of anti-infective drugs and vaccination and could open a avenue for application of PurA in the regulation of T3SS.


Assuntos
Aurodox , Sistemas de Secreção Tipo III , Sistemas de Secreção Tipo III/metabolismo , Aurodox/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas/metabolismo , Proteínas de Bactérias/metabolismo
2.
Nature ; 585(7826): 591-596, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526765

RESUMO

Recent clinical and experimental evidence has evoked the concept of the gut-brain axis to explain mutual interactions between the central nervous system and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel disease and central nervous system disorders1-4. Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including in the induction and maintenance of peripheral regulatory T cells (pTreg cells), and what environmental cues prompt the host to protect itself from development of inflammatory bowel diseases. Here we report a liver-brain-gut neural arc that ensures the proper differentiation and maintenance of pTreg cells in the gut. The hepatic vagal sensory afferent nerves are responsible for indirectly sensing the gut microenvironment and relaying the sensory inputs to the nucleus tractus solitarius of the brainstem, and ultimately to the vagal parasympathetic nerves and enteric neurons. Surgical and chemical perturbation of the vagal sensory afferents at the hepatic afferent level reduced the abundance of colonic pTreg cells; this was attributed to decreased aldehyde dehydrogenase (ALDH) expression and retinoic acid synthesis by intestinal antigen-presenting cells. Activation of muscarinic acetylcholine receptors directly induced ALDH gene expression in both human and mouse colonic antigen-presenting cells, whereas genetic ablation of these receptors abolished the stimulation of antigen-presenting cells in vitro. Disruption of left vagal sensory afferents from the liver to the brainstem in mouse models of colitis reduced the colonic pTreg cell pool, resulting in increased susceptibility to colitis. These results demonstrate that the novel vago-vagal liver-brain-gut reflex arc controls the number of pTreg cells and maintains gut homeostasis. Intervention in this autonomic feedback feedforward system could help in the development of therapeutic strategies to treat or prevent immunological disorders of the gut.


Assuntos
Encéfalo/citologia , Intestinos/citologia , Intestinos/inervação , Fígado/citologia , Fígado/inervação , Neurônios/fisiologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Vias Aferentes , Animais , Células Apresentadoras de Antígenos/imunologia , Colite/imunologia , Colite/metabolismo , Colite/patologia , Homeostase , Humanos , Intestinos/imunologia , Masculino , Camundongos , Ratos , Receptores Muscarínicos/metabolismo , Baço/citologia , Baço/imunologia , Nervo Vago/fisiologia
3.
EMBO Rep ; 24(7): e56574, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37212043

RESUMO

Dysregulation of the activity of the mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to aging, cancer, and genetic disorders such as tuberous sclerosis (TS), a rare neurodevelopmental multisystemic disease characterized by benign tumors, seizures, and intellectual disability. Although patches of white hair on the scalp (poliosis) are considered as early signs of TS, the underlying molecular mechanisms and potential involvement of mTORC1 in hair depigmentation remain unclear. Here, we have used healthy, organ-cultured human scalp hair follicles (HFs) to interrogate the role of mTORC1 in a prototypic human (mini-)organ. Gray/white HFs exhibit high mTORC1 activity, while mTORC1 inhibition by rapamycin stimulated HF growth and pigmentation, even in gray/white HFs that still contained some surviving melanocytes. Mechanistically, this occurred via increased intrafollicular production of the melanotropic hormone, α-MSH. In contrast, knockdown of intrafollicular TSC2, a negative regulator of mTORC1, significantly reduced HF pigmentation. Our findings introduce mTORC1 activity as an important negative regulator of human HF growth and pigmentation and suggest that pharmacological mTORC1 inhibition could become a novel strategy in the management of hair loss and depigmentation disorders.


Assuntos
Folículo Piloso , Pigmentação , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Pigmentação/genética , Melanócitos , Cor de Cabelo/genética
4.
Br J Haematol ; 204(5): 2086-2096, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38296352

RESUMO

Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients. The present study included 100 eligible AA patients without ring sideroblasts. Among them, 32 had dysplasia in the erythroid lineage (AA with minimal dysplasia [mini-D]). No significant sex or age differences were observed between AA groups with and without erythroid dysplasia. In severe/very severe AA and non-severe AA patients, a response to anti-thymocyte globulin + ciclosporin within 12 months was observed in 80.0% and 60.0% of AA with mini-D and 42.9% and 90.0% of those without dysplasia, with no significant difference (p = 0.29 and p = 0.24 respectively). Overall survival and leukaemia-free survival did not significantly differ between the groups. Collectively, the present results indicate that the presence of erythroid dysplasia did not significantly affect clinical characteristics or outcomes in AA patients, suggesting that its presence in AA is acceptable. Therefore, erythroid dysplasia should not exclude an AA diagnosis.


Assuntos
Anemia Aplástica , Sistema de Registros , Humanos , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , Anemia Aplástica/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Células Eritroides/patologia , Adolescente , Idoso de 80 Anos ou mais
5.
Biochem Biophys Res Commun ; 696: 149488, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38219485

RESUMO

Enzymatic methyl-seq (EM-seq), an enzyme-based method, identifies genome-wide DNA methylation, which enables us to obtain reliable methylome data from purified genomic DNA by avoiding bisulfite-induced DNA damage. However, the loss of DNA during purification hinders the methylome analysis of limited samples. The crude DNA extraction method is the quickest and minimal sample loss approach for obtaining useable DNA without requiring additional dissolution and purification. However, it remains unclear whether crude DNA can be used directly for EM-seq library construction. In this study, we aimed to assess the quality of EM-seq libraries prepared directly using crude DNA. The crude DNA-derived libraries provided appropriate fragment sizes and concentrations for sequencing similar to those of the purified DNA-derived libraries. However, the sequencing results of crude samples exhibited lower reference sequence mapping efficiencies than those of the purified samples. Additionally, the lower-input crude DNA-derived sample exhibited a marginally lower cytosine-to-thymine conversion efficiency and hypermethylated pattern around gene regulatory elements than the higher-input crude DNA- or purified DNA-derived samples. In contrast, the methylation profiles of the crude and purified samples exhibited a significant correlation. Our findings indicate that crude DNA can be used as a raw material for EM-seq library construction.


Assuntos
Metilação de DNA , DNA , Biblioteca Gênica , Sequência de Bases , DNA/genética , DNA/análise , Clonagem Molecular , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sulfitos
6.
Am J Pathol ; 193(5): 591-607, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36773783

RESUMO

α-Klotho is a longevity-related protein. Its deficiency shortens lifespan with prominent senescent phenotypes, including muscle atrophy and weakness in mice. α-Klotho has two forms: membrane α-Klotho and circulating α-Klotho (c-α-Klotho). Loss of membrane α-Klotho impairs a phosphaturic effect, thereby accelerating phosphate-induced aging. However, the mechanisms of senescence on c-α-Klotho loss remain largely unknown. Herein, with the aging of wild-type mice, c-α-Klotho declined, whereas Smad2, an intracellular transforming growth factor (TGF)-ß effector, became activated in skeletal muscle. Moreover, c-α-Klotho suppressed muscle-wasting TGF-ß molecules, including myostatin, growth and differentiation factor 11, activin, and TGF-ß1, through binding to ligands as well as type I and type II serine/threonine kinase receptors. Indeed, c-α-Klotho reversed impaired in vitro myogenesis caused by these TGF-ßs. Oral administration of Ki26894, a small-molecule inhibitor of type I receptors for these TGF-ßs, restored muscle atrophy and weakness in α-Klotho (-/-) mice and in elderly wild-type mice by suppression of activated Smad2 and up-regulated Cdkn1a (p21) transcript, a target of phosphorylated Smad2. Ki26894 also induced the slow to fast myofiber switch. These findings show c-α-Klotho's potential as a circulating inhibitor counteracting TGF-ß-induced sarcopenia. These data highlight the potential of a novel therapy involving TGF-ß blockade to prevent sarcopenia.


Assuntos
Sarcopenia , Fator de Crescimento Transformador beta , Camundongos , Animais , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Sarcopenia/prevenção & controle , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fatores de Crescimento Transformadores
7.
Cell Tissue Res ; 396(2): 231-243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438567

RESUMO

C-C motif chemokine ligand 2 (CCL2) has been reported to be expressed in the bovine endometrium during pregnancy. However, the details of its functions involved in the implantation mechanism are still not clear. The purpose of this study is to analyze the functional properties of CCL2 in the bovine endometrium and embryos. The expression of CCR2 was not different between the luteal phase and implantation phase of their endometrial tissues, but was significantly high in IFNa treated bovine endometrial stromal (BES) cells in vitro. The expressions of PGES1, PGES2, AKR1C4, and AKR1C4 were high at the implantation stage compared with the luteal stage. On the other hand, PGES2 and AKR1B1 in BEE and PGES3 and AKR1A1 in BES were significantly increased by CCL2 treatment, respectively. The expressions of PCNA and IFNt were found significantly high in the bovine trophoblastic cells (BT) treated with CCL2 compared to the control. CCL2 significantly increased the attachment rate of BT vesicles to BEE in in vitro co-culture system. The expression of OPN and ICAM-1 increased in BEE, and ICAM-1 increased in BT by CCL2 treatment, respectively. The present results indicate that CCL2 has the potential to regulate the synthesis of PGs in the endometrium and the embryo growth. In addition, CCL2 has the possibility to regulate the process of bovine embryo attachment to the endometrium by modulation of binding molecules expression.


Assuntos
Quimiocina CCL2 , Implantação do Embrião , Endométrio , Prostaglandinas , Animais , Bovinos , Feminino , Gravidez , Quimiocina CCL2/metabolismo , Implantação do Embrião/genética , Endométrio/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interferon Tipo I , Proteínas da Gravidez , Prostaglandinas/metabolismo , Receptores CCR2/metabolismo , Células Estromais/metabolismo , Trofoblastos/metabolismo , Trofoblastos/citologia
8.
J Autoimmun ; 145: 103217, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581915

RESUMO

The autoimmunity-promoting cytokine, Interleukin-15 (IL-15), is often claimed to be a key pathogenic cytokine in alopecia areata (AA). Yet, rhIL-15 promotes human hair follicle (HF) growth ex vivo. We have asked whether the expression of IL-15 and its receptor (IL-15R) isoforms is altered in human AA and how IL-15 impacts on human HF immune privilege (HF-IP) in the presence/absence of interferon-γ (IFNγ), the well-documented key AA-pathogenic cytokine, as well as on hair regrowth after experimental AA induction in vivo. Quantitative immunohistomorphometry showed the number of perifollicular IL-15+ T cells in AA skin biopsies to be significantly increased compared to healthy control skin, while IL-15, IL-15Rα, and IL-15Rγ protein expression within the hair bulb were significantly down-regulated in AA HFs. In organ-cultured human scalp HFs, rhIL-15 significantly reduced hair bulb expression of MICA, the key "danger" signal in AA pathogenesis, and increased production of the HF-IP guardian, α-MSH. Crucially, ex vivo, rhIL-15 prevented IFNγ-induced HF-IP collapse, restored a collapsed HF-IP by IL-15Rα-dependent signaling (as documented by IL-15Rα-silencing), and protected AA-preventive immunoinhibitory iNKT10 cells from IFNγ-induced apoptosis. rhIL-15 even promoted hair regrowth after experimental AA induction in human scalp skin xenotransplants on SCID/beige mice in vivo. Our data introduce IL-15 as a novel, functionally important HF-IP guardian whose signaling is constitutively defective in scalp HFs of AA patients. Our data suggest that selective stimulation of intrafollicular IL-15Rα signaling could become a novel therapeutic approach in AA management, while blocking it pharmacologically may hinder both HF-IP restoration and hair re-growth and may thus make HFs more vulnerable to AA relapse.


Assuntos
Alopecia em Áreas , Folículo Piloso , Privilégio Imunológico , Interferon gama , Interleucina-15 , Interleucina-15/metabolismo , Interleucina-15/imunologia , Folículo Piloso/imunologia , Folículo Piloso/metabolismo , Humanos , Animais , Alopecia em Áreas/imunologia , Alopecia em Áreas/metabolismo , Camundongos , Interferon gama/metabolismo , Feminino , Receptores de Interleucina-15/metabolismo , Receptores de Interleucina-15/imunologia , Masculino , Adulto , Pessoa de Meia-Idade , Subunidade alfa de Receptor de Interleucina-15/metabolismo , Subunidade alfa de Receptor de Interleucina-15/imunologia , Pele/imunologia , Pele/metabolismo , Pele/patologia , Modelos Animais de Doenças
9.
Chemistry ; : e202401908, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770667

RESUMO

We describe a method for the synthesis of various 2-silyloxy-2-norbornen-7-ones by exploiting the specific reactivity of the 1,4-bis(silyloxy)-1,3-cyclopentadiene framework, which is generated by the silylation of a 2,2-disubstituted-1,3-cyclopentanedione bearing a picolinoyloxy group at the 2' position of its C-2 side chain. The release of the acyloxy group during the reaction generates carbocations that are then attacked by silyloxy-substituted carbons in the 1,4-bis(silyloxy)-1,3-cyclopentadiene moiety skeleton, forming a 4,5-cis-fused ring skeleton. Skeletal rearrangement of the bicyclic core results in the formation of the corresponding 2-silyloxy-2-norbornen-7-one. This novel transformation of 1,3-cyclopentanedione moieties can be used to synthesise other cyclopentenone-fused bicyclic frameworks.

10.
Org Biomol Chem ; 22(7): 1369-1373, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38232248

RESUMO

A convenient method has been developed for transforming alkyl halides into the corresponding alcohols via an SN2 reaction. Treatment of an alkyl halide with the squarate dianion at high temperature produces mono-alkyl squarate, and a one-pot basic hydrolysis of the intermediate affords the alcohol in good yield.

11.
Org Biomol Chem ; 22(23): 4637-4640, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38716558

RESUMO

Jamaicamide B was isolated from the cyanobacterium Moorea producens in Jamaica and shows neurotoxicity. This unique mixed peptide-polyketide structure contains a pyrrolinone ring, a ß-methoxy enone, an (E)-olefin, an undetermined stereocenter at C9, an (E)-chloroolefin, and a terminal alkyne. We report herein the first total synthesis and structural confirmation of the marine natural product (9R)-jamaicamide B.


Assuntos
Cianobactérias , Cianobactérias/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Estereoisomerismo , Estrutura Molecular
12.
Circ J ; 88(3): 390-407, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38072415

RESUMO

BACKGROUND: Despite the importance of implementing the concept of social determinants of health (SDOH) in the clinical practice of cardiovascular disease (CVD), the tools available to assess SDOH have not been systematically investigated. We conducted a scoping review for tools to assess SDOH and comprehensively evaluated how these tools could be applied in the field of CVD.Methods and Results: We conducted a systematic literature search of PubMed and Embase databases on July 25, 2023. Studies that evaluated an SDOH screening tool with CVD as an outcome or those that explicitly sampled or included participants based on their having CVD were eligible for inclusion. In addition, studies had to have focused on at least one SDOH domain defined by Healthy People 2030. After screening 1984 articles, 58 articles that evaluated 41 distinct screening tools were selected. Of the 58 articles, 39 (67.2%) targeted populations with CVD, whereas 16 (27.6%) evaluated CVD outcome in non-CVD populations. Three (5.2%) compared SDOH differences between CVD and non-CVD populations. Of 41 screening tools, 24 evaluated multiple SDOH domains and 17 evaluated only 1 domain. CONCLUSIONS: Our review revealed recent interest in SDOH in the field of CVD, with many useful screening tools that can evaluate SDOH. Future studies are needed to clarify the importance of the intervention in SDOH regarding CVD.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Determinantes Sociais da Saúde , Bases de Dados Factuais , Nível de Saúde
13.
J Gastroenterol Hepatol ; 39(3): 480-488, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38149305

RESUMO

BACKGROUND AND AIM: Potassium-competitive acid blockers more strongly suppress the gastric acid barrier than proton pump inhibitors and cause dysbiosis. However, preventive measures in this regard have not been established. We aimed to evaluate whether 1-kestose, a known prebiotic, was effective at alleviating dysbiosis caused by potassium-competitive acid blockers. METHODS: Patients scheduled to undergo endoscopic resection for superficial gastroduodenal tumors were enrolled and randomized 1:1 to receive either 1-kestose or placebo. All patients were started on potassium-competitive acid blocker (vonoprazan 20 mg/day) and took 1-kestose 10 g/day or placebo (maltose) 5 g/day for 8 weeks. The primary outcome was the effect of 1-kestose on potassium-competitive acid blocker-induced alterations in the microbiome. The fecal microbiome was analyzed before and after potassium-competitive acid blocker treatment via MiSeq (16S rRNA gene V3-V4 region). RESULTS: Forty patients were enrolled, and 16 in each group were analyzed. In the placebo group, the Simpson index, an alpha diversity, was significantly decreased and relative abundance of Streptococcus was significantly increased by 1.9-fold. In the kestose group, the Simpson index did not change significantly and relative abundance of Streptococcus increased 1.3-fold, but this was not a significant change. In both groups, no adverse events occurred, ulcers were well healed, and pretreatment and posttreatment short-chain fatty acid levels did not differ. CONCLUSIONS: The potassium-competitive acid blocker caused dysbiosis in the placebo group; this effect was prevented by 1-kestose. Thus, 1-kestose may be useful in dysbiosis treatment.


Assuntos
Disbiose , Microbiota , Pirróis , Sulfonamidas , Trissacarídeos , Humanos , Disbiose/etiologia , RNA Ribossômico 16S , Projetos Piloto , Inibidores da Bomba de Prótons/efeitos adversos , Potássio
14.
Exp Cell Res ; 430(1): 113698, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37437770

RESUMO

Satellite cells are indispensable for skeletal muscle regeneration and hypertrophy by forming nascent myofibers (myotubes). They synthesize multi-potent modulator netrins (secreted subtypes: netrin-1, -3, and -4), originally found as classical neural axon guidance molecules. While netrin-1 and -3 have key roles in myogenic differentiation, the physiological significance of netrin-4 is still unclear. This study examined whether netrin-4 regulates myofiber type commitment and myotube formation. Initially, the expression profiles indicated that satellite cells isolated from the extensor digitorum longus muscle (EDL muscle: fast-twitch myofiber-abundant) expressed slightly more netrin-4 than the soleus muscle (slow-type abundant) cells. As netrin-4 knockdown inhibited both slow- and fast-type myotube formation, netrin-4 may not directly regulate myofiber type commitment. However, netrin-4 knockdown in satellite cell-derived myoblasts reduced the myotube fusion index, while exogenous netrin-4 promoted myotube formation, even though netrin-4 expression level was maximum during the initiation stage of myogenic differentiation. Furthermore, netrin-4 knockdown also inhibited MyoD (a master transcriptional factor of myogenesis) and Myomixer (a myoblast fusogenic molecule) expression. These data suggest that satellite cells synthesize netrin-4 during myogenic differentiation initiation to promote their own fusion, stimulating the MyoD-Myomixer signaling axis.


Assuntos
Fibras Musculares Esqueléticas , Células Satélites de Músculo Esquelético , Netrina-1/metabolismo , Células Cultivadas , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Diferenciação Celular/fisiologia , Células Satélites de Músculo Esquelético/metabolismo
15.
Biosci Biotechnol Biochem ; 88(5): 509-516, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38425056

RESUMO

Nutrient availability in hydroponic solutions must be accurately monitored to maintain crop productivity; however, few cost-effective, accurate, real-time, and long-term monitoring technologies have been developed. In this study, we describe the development and application of cation-/anion-exchange chromatography with a neutral eluent (20-mmol/L sodium formate, pH 7.87) for the simultaneous separation (within 50 min) of ionic nutrients, including K+, NH4+, NO2-, NO3-, and phosphate ion, in a hydroponic fertilizer solution. Using the neutral eluent avoided degradation of the separation column during precipitation of metal ion species, such as hydroxides, with an alkaline eluent and oxidation of NO2- to NO3- with an acidic eluent. The suitability of the current method for monitoring ionic components in a hydroponic fertilizer solution was confirmed. Based on our data, we propose a controlled fertilizer strategy to optimize fertilizer consumption and reduce the chemical load of drained fertilizer solutions.


Assuntos
Fertilizantes , Hidroponia , Soluções , Hidroponia/métodos , Cromatografia por Troca Iônica/métodos , Fertilizantes/análise , Nutrientes/análise , Cátions/análise , Fosfatos/análise , Concentração de Íons de Hidrogênio , Potássio/análise
16.
World J Surg Oncol ; 22(1): 160, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902721

RESUMO

BACKGROUND: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and is known to be associated with Sjögren's syndrome (SjS). SjS is rarely accompanied by serositis. Here, we describe the first case of postoperative cardiac tamponade and acute pleuritis in a patient with thymic MALT lymphoma associated with SjS. CASE PRESENTATION: A 33-year-old woman with SjS presented with an anterior mediastinal mass on chest computed tomography, which was performed for further examination of the condition. Suspecting a thymic MALT lymphoma or thymic epithelial tumor, total thymectomy was performed. The mediastinal mass was histopathologically diagnosed as a thymic MALT lymphoma. The patient was discharged with a good postoperative course but visited the hospital 30 days after surgery for dyspnea. Cardiac tamponade was observed and drainage was performed. Four days after pericardial drainage, chest radiography revealed massive left pleural effusion, and thoracic drainage was performed. The patient was diagnosed with serositis associated with SjS and treated with methylprednisolone, which relieved cardiac tamponade and pleuritis. CONCLUSIONS: Surgical invasion of thymic MALT lymphomas associated with SjS may cause serositis. Postoperative follow-up should be conducted, considering the possibility of cardiac tamponade or acute pleuritis due to serositis as postoperative complications.


Assuntos
Tamponamento Cardíaco , Linfoma de Zona Marginal Tipo Células B , Pleurisia , Complicações Pós-Operatórias , Síndrome de Sjogren , Neoplasias do Timo , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/cirurgia , Linfoma de Zona Marginal Tipo Células B/patologia , Feminino , Adulto , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/cirurgia , Tamponamento Cardíaco/diagnóstico , Síndrome de Sjogren/complicações , Pleurisia/etiologia , Neoplasias do Timo/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Complicações Pós-Operatórias/etiologia , Timectomia/efeitos adversos , Prognóstico , Tomografia Computadorizada por Raios X , Doença Aguda
17.
Tohoku J Exp Med ; 262(2): 105-113, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38092409

RESUMO

Parotid tumors present a wide range of histological features, from benign to malignant. Periostin, an extracellular matrix protein specifically expressed in the periosteum and periodontal ligament, is isolated from osteoblast cell lines. It regulates fibrosis and collagen deposition and plays an important role in myocardial repair after myocardial infarction. It is also known to be involved in otorhinolaryngological-diseases. This study included 36 patients [38 specimens; 16 men and 20 women, mean age 59.2 (range 26-82) years] who underwent parotid tumor resection at the Division of Otorhinolaryngology, Tohoku Medical and Pharmaceutical University, between April 2017 and March 2022 and were clinically and pathologically diagnosed as having benign parotid tumors. Formalin-fixed, paraffin-embedded sections from the surgical specimens were autoclaved and immunostained with anti-periostin antibodies to evaluate the expression and distribution of periostin. Histologically, the tumors were diagnosed as pleomorphic adenomas in 15 cases (15 specimens), Warthin's tumors in 13 cases (15 specimens), basal cell adenomas in 2 cases (2 specimens), oncocytomas in 4 cases (4 specimens), and myoepitheliomas in 2 cases (2 specimens). An increased expression of periostin was found in 32 of 38 samples (84.2%) in the stroma of benign parotid tumors. Four distinct patterns of periostin expression were observed in benign parotid gland tumors: negative, superficial, infiltrative, and diffuse. Statistically significant differences were found between periostin expression patterns and histological classification of the tumors. Our results suggest that periostin may be involved in the pathogenesis of benign parotid tumors and could serve as a new biomarker for these tumors.


Assuntos
Adenoma Pleomorfo , Adenoma , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/metabolismo , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Neoplasias Parotídeas/metabolismo , Neoplasias Parotídeas/patologia , Periostina , Neoplasias das Glândulas Salivares/metabolismo
18.
Surg Today ; 54(7): 787-794, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38416144

RESUMO

PURPOSE: Surgical patients with thymoma and myasthenia gravis (MG) must have their MG status and oncological outcomes critically monitored. We aimed to identify clinicopathological predictors of the postoperative MG status. METHODS: We conducted a retrospective review of 40 consecutive surgical patients with MG-related thymomas between 2002 and 2020. The quantitative myasthenia gravis score (QMGS) and Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS) were used to evaluate postoperative MG status. RESULTS: All patients underwent extended total thymectomy. The most common WHO type was type B2 (32%), while 65% of patients had type B1-B3 and 35% had type A-AB thymomas. Eleven patients (28%) achieved controlled MG status in MGFA-PIS 6 months after surgery. This controlled status was observed more frequently in type A-AB than in B1-B3 (57% vs. 12%, p = 0.007). In a multivariate analysis, WHO type (A-AB or B1-B3) was an independent predictor of worsening episodes of MG based on the QMGS (Type B1-B3, hazard ratio: 3.23, 95% confidence interval: 1.12-9.25). At the last follow-up, 23 patients (58%) achieved controlled MG status. The 5-year overall survival rate of all patients was 93.7%. CONCLUSION: The WHO type of thymoma is an informative predictor of postoperative MG status in patients with MG-related thymoma.


Assuntos
Miastenia Gravis , Timectomia , Timoma , Neoplasias do Timo , Humanos , Miastenia Gravis/cirurgia , Miastenia Gravis/complicações , Timoma/cirurgia , Timoma/complicações , Timoma/patologia , Timoma/mortalidade , Timectomia/métodos , Estudos Retrospectivos , Neoplasias do Timo/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Neoplasias do Timo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Tempo , Idoso , Período Pós-Operatório , Adulto , Resultado do Tratamento
19.
Int Heart J ; 65(1): 100-108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38296562

RESUMO

The effectiveness of gamification-based feedback systems that utilize non-monetary points to promote exercise among cardiovascular disease (CVD) patients has not been fully evaluated. This study aimed to evaluate the effectiveness of a gamification program using non-monetary points on the daily step counts in CVD patients. We collected 30 patients with a history of heart failure or myocardial infarction at a single tertiary center between January 9, 2023, and April 13, 2023. The primary outcome was the change in daily step counts. The baseline step counts were compared with those during the 4-week gamification and the 1-week follow-up period. A total of 29 participants with a mean age of 64.6 years were finally enrolled, and 8 (27.6%) were female. Among them, 23 (79.3%) had a history of old myocardial infarction, and 9 (31.0%) had a history of chronic heart failure. During the intervention period, the average daily step counts increased significantly from baseline in weeks 1-5 (week 1: 1165 steps; 95% CI, 319-2011; P = 0.009, week 2: 1508; 635-2382; P = 0.001, week 3: 1321; 646-1996; P < 0.001, week 4: 1436; 791-2081; P < 0.001, week 5:1148; 436-1860; P < 0.001). Higher body mass index was statistically associated with the smaller difference in step counts from the baseline, and the lower proportion of achievement of step count goals. Female sex was significantly associated with the higher proportion of achievement of step count goals. In conclusion, this pilot prospective interventional study demonstrated the effectiveness of gamification-based feedback systems that utilize non-monetary points to increase daily step counts in CVD patients.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Retroalimentação , Economia Comportamental , Estudos Prospectivos
20.
Rev Esp Enferm Dig ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450507

RESUMO

Ectopic pancreas (EP) is defined as pancreatic tissue that lacks anatomical or vascular connections to the normal pancreas. EP is generally asymptomatic and is detected incidentally during endoscopy. However, due to pseudocyst formation, inflammation, or malignant transformation, it may cause non-specific gastrointestinal symptoms, such as abdominal pain, abdominal discomfort, nausea, vomiting, and bleeding. Pseudocyst formation in EP may result from the retention of exocrine secretions in the absence of connections between the glandular epithelium and gastric lumen. We herein report a case of EP with a pseudocyst associated with epigastric pain. EP with a pseudocyst, although rare, needs to be considered in a differential diagnosis of cystic lesions of the stomach.

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