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1.
World J Gastroenterol ; 30(18): 2402-2417, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764770

RESUMO

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.


Assuntos
Antivirais , Hepatite Viral Humana , Humanos , Antivirais/uso terapêutico , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/virologia , Hepatite Viral Humana/terapia , Hepatite Viral Humana/diagnóstico , Vírus de Hepatite/patogenicidade , Vírus de Hepatite/efeitos dos fármacos , Vírus de Hepatite/genética , Prevalência , Fígado/virologia , Fígado/patologia
2.
Respirol Case Rep ; 12(5): e01392, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799121

RESUMO

Cavitary lung lesions are uncommon radiological findings in cytomegalovirus pneumonia, and tissue biopsy is rarely performed for diagnosis. A 67-year-old man presented with a wet cough. Extensive white moss in the oral cavity was found on physical examination, and chest computed tomography revealed an approximately 4 cm cavitary lesion in the upper lobe of the right lung. Blood tests showed a critically low CD4+ T lymphocyte count and positivity for human immunodeficiency virus type 1 antibodies. A transbronchial biopsy of the cavitary lung lesion was performed, and inclusion bodies in the nuclei of enlarged alveolar epithelial cells were seen in the histopathological findings. Immunohistochemistry staining for cytomegalovirus was positive, and cytomegalovirus pneumonia was diagnosed. Ganciclovir treatment was initiated, and the symptoms and imaging findings resolved. Cytomegalovirus pneumonia can present as cavitary lung lesions in patients with acquired immunodeficiency syndrome, and a transbronchial biopsy is essentially useful for a definitive diagnosis.

3.
Respir Med Case Rep ; 50: 102037, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803367

RESUMO

A 65-year-old man with dyspnea and hemoptysis presented with a right upper lobe mass associated with enlarged mediastinal lymph nodes and bilateral pulmonary nodules on chest computed tomography (CT), suspected lung cancer. Bronchial and CT-guided biopsies revealed poorly differentiated carcinoma. His condition deteriorated rapidly before a definitive diagnosis could be made. Autopsy revealed primary mediastinal choriocarcinoma. Primary mediastinal choriocarcinomas are rare, difficult to diagnose early and have a poor prognosis. In patients with a tumor expanding across the lung and mediastinum and exhibiting pathologic findings of a pooly differentiated carcinoma, we should consider choriocarcinoma, evaluating the serum ß-human chorionic gonadotropin levels.

4.
Microbiologyopen ; 13(2): e1399, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38436548

RESUMO

Gene sequence has been widely used in molecular ecology. For instance, the ribosomal RNA (rRNA) gene has been widely used as a biological marker to understand microbial communities. The variety of the detected rRNA gene sequences reflects the diversity of the microorganisms existing in the analyzed sample. Their biomass can also be estimated by applying quantitative sequencing with information on rRNA gene copy numbers in genomes; however, information on rRNA gene copy numbers is still limited. Especially, the copy number in microbial eukaryotes is much less understood than that of prokaryotes, possibly because of the large and complex structure of eukaryotic genomes. In this study, we report an alternative approach that is more appropriate than the existing method of quantitative sequencing and demonstrate that the copy number of eukaryotic rRNA can be measured efficiently and comprehensively. By applying this approach widely, information on the eukaryotic rRNA copy number can be determined, and their community structures can be depicted and compared more efficiently.


Assuntos
Variações do Número de Cópias de DNA , Microbiota , Genes de RNAr , Biomassa , Dosagem de Genes , RNA Ribossômico/genética
5.
Respir Investig ; 62(1): 13-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37925883

RESUMO

Osimertinib has demonstrated efficacy as the first- and second-line treatment for advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. However, EGFR-mutant NSCLC cells often acquire resistance to osimertinib. V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (BRAF V600E) was detected in a re-biopsy (LC-SCRUM-TRY testing) of a patient with advanced lung adenocarcinoma who was resistant to osimertinib treatment. Currently, the patient is receiving dabrafenib/trametinib combination therapy and is under observation; a slight shrinking effect of cancer has been observed.


Assuntos
Acrilamidas , Adenocarcinoma de Pulmão , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética , Mutação , Oncogenes , Inibidores de Proteínas Quinases
6.
Vaccine ; 42(3): 677-688, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38114409

RESUMO

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Oxigênio/uso terapêutico , Japão/epidemiologia , Respiração Artificial , Estudos de Casos e Controles , Eficácia de Vacinas , SARS-CoV-2
7.
Ann Thorac Cardiovasc Surg ; 30(1)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38105006

RESUMO

PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Tegafur/efeitos adversos , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Adenocarcinoma/patologia , Genes erbB-1 , Resultado do Tratamento , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Prognóstico , Mutação , Receptores ErbB/genética , Estadiamento de Neoplasias , Quimioterapia Adjuvante
8.
Cancers (Basel) ; 15(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38067275

RESUMO

Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.

9.
World J Clin Cases ; 11(24): 5811-5816, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37727727

RESUMO

BACKGROUND: Penoscrotal constriction devices are either used as autoerotic stimuli or to increase sexual pleasure or performance by maintaining an erection for a longer period, and a variety of metallic and non-metallic objects are used. On the other hand, penile strangulation is a rare urologic emergency that requires prompt evaluation and intervention to prevent long-term complications. The goal of treating penile incarceration is to remove the foreign object as soon as possible. On the other hand, removal can be very challenging, and often requires resourcefulness and a multidisciplinary approach. CASE SUMMARY: A 47-year-old man who has sex with men was transferred to our hospital for persistent phallodynia and scrotal pain, accompanying swelling due to strangulation by stainless steel rings. His medical history included acquired immunodeficiency syndrome. One day prior, he had put three stainless steel rings on his penis and scrotum before sexual intercourse. After sexual intercourse, he was unable to remove them, due to swelling of his penis and scrotum. The swelling persisted, and he felt pain in the affected area the next day, then he was transferred to our hospital by ambulance. The emergency department found that his penis and scrotum were markedly engorged and swollen. We established a diagnosis of penile and scrotal strangulation by stainless steel rings. We unsuccessfully attempted to cut the rings using a cutter, then requested a rescue team via emergency medical service. They cut through each ring in two places, using an electric-powered angle grinder, and successfully removed all of the pieces. Finally, he was discharged and went home. CONCLUSION: We report the first case of penile and scrotal strangulation by stainless steel rings in an human immunodeficiency virus positive person.

10.
World J Clin Cases ; 11(26): 6280-6288, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37731582

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated invasive pulmonary aspergillosis presents a diagnostic challenge due to its non-specific clinical/ imaging features, as well as the fact that the proposed clinically diagnostic algorithms do not necessarily apply to COVID-19 patients. In addition, Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. Disseminated Fusarium infection in an immunocompromised host is intractable, with a high likelihood of resulting mortality. To our knowledge, this is the first case of secondary pulmonary infection by Fusarium solani (F. solani) and Aspergillus niger (A. niger) during systemic steroid treatment for COVID-19. CASE SUMMARY: A 62-year-old male was transported to our hospital by ambulance with a complaint of fever and dyspnea. We established a diagnosis of pneumococcal pneumonia, complicated with COVID-19 and septic shock, together with acute renal failure. He was admitted to the intensive care unit, to be treated with piperacillin/tazobactam, vancomycin, and 6.6 mg per day of dexamethasone sodium phosphate, along with noradrenaline as a vasopressor, ventilator management, and continuous hemodiafiltration. His condition improved, and we finished the vasopressor on the fifth hospital day. We administered dexamethasone for ten days, and finished the course of treatment. On the eleventh day, patient respiratory deterioration was observed, and a computed tomography scan showed an exacerbation of bilateral ground-glass-opacity-like consolidation, together with newly appeared cavitary lesions in the lung. we changed antibiotics to meropenem plus vancomycin. In addition, a fungal infection was considered as a possibility based on microscopic findings of sputum, and we began coadministration of voriconazole. However, the pneumonia worsened, and the patient died on the seventeenth day of illness. Later, F. solani and A. niger were identified from sputum collected on the twelfth day. It was believed that he developed a cell-mediated immune deficiency during COVID-19 treatment, which led to the complication of pneumonia caused by the above-mentioned fungi, contributing to his death. CONCLUSION: Because early initiation of intense antifungal therapy offers the best chance for survival in pulmonary fusariosis, computed tomography scans and appropriate microbiologic investigations should be obtained for severely immunocompromised patients.

11.
Cells ; 12(14)2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37508549

RESUMO

The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downregulated in LUAD tissues. Ectopic expression of both miRNAs induced cell cycle arrest in LUAD cells, suggesting both strands of miRNAs derived from pre-miR-486 were tumor suppressive. Our in silico analysis showed a total of 99 genes may be under the control of both miRNAs in LUAD cells. Importantly, among these targets, the high expression of seven genes (MKI67, GINS4, RRM2, HELLS, MELK, TIMELESS, and SAPCD2) predicted a poorer prognosis of LUAD patients (p < 0.05). We focused on GINS4, a DNA replication complex GINS protein that plays an essential role in the initiation of DNA replication. Our functional assays showed that GINS4 was directly controlled by both strands of pre-miR-486, and its aberrant expression facilitated the aggressive behavior of LUAD cells. GINS4 is attractive as a therapeutic target for this disease. MiRNA analysis, including passenger strands, will further improve our understanding of the molecular pathogenesis of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Humanos , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Proliferação de Células/genética , Neoplasias Pulmonares/genética , Proteínas Serina-Treonina Quinases , Proteínas Cromossômicas não Histona/genética , Proteínas Nucleares
12.
FEBS Open Bio ; 13(9): 1737-1755, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37517032

RESUMO

Lung cancer is the most common cause of cancer-related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2-MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (P = 0.0032), MCM5 (P = 0.0032), and MCM7 (P = 0.0110) significantly predicted 5-year survival rates in patients with LUAD. Simurosertib (TAK-931) significantly suppressed the proliferation of LUAD cells by inhibiting cell division cycle 7-mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR-139-3p, miR-378a-5p, and miR-2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Humanos , Relevância Clínica , Epigênese Genética , Adenocarcinoma de Pulmão/metabolismo , Proteínas de Manutenção de Minicromossomo/genética , Proteínas de Manutenção de Minicromossomo/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo
13.
Int J Mol Sci ; 24(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37511342

RESUMO

Thallium (Tl), is a highly toxic heavy metal that exists in monovalent (Tl(I)) and trivalent (Tl(III)) ionic states. This study aimed to compare the toxicities of Tl(I) and Tl(III) in a mouse hypothalamic GT1-7 neuronal cell line. Decreased viability and increased cytotoxicity were observed in the GT1-7 cells 16 h after Tl(I) or Tl(III) treatment. Tl(III) was more cytotoxic, than Tl(I), as indicated by extracellular lactate dehydrogenase levels. Both treatments induced caspase 3 activity, DNA fragmentation, malondialdehyde (MDA) production, and superoxide dismutase activity in the cells. MDA production was higher after Tl(III) than after Tl(I) treatment. Moreover, co-treatment with antioxidants, such as mannitol, ascorbic acid, or tocopherol, significantly attenuated the Tl-induced decrease in GT1-7 cell numbers. Therefore, both treatments induced oxidative stress-related apoptosis. Furthermore, Tl(III) reduced the cell viability more subtly than Tl(I) after 1 and 3 h of treatment. This effect was enhanced by co-treatment with maltol or citric acid, which promoted the influx of metallic elements into the cells. Thus, Tl(III) entered GT1-7 cells later than Tl(I) and had a delayed onset of toxicity. However, Tl(III) likely produces more extracellular lipid peroxides, which may explain its stronger cytotoxicity.


Assuntos
Antioxidantes , Tálio , Animais , Camundongos , Tálio/farmacologia , Oxirredução , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Apoptose
14.
World J Clin Cases ; 11(16): 3870-3876, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37383112

RESUMO

BACKGROUND: Dextromethorphan is a prevalent antitussive agent that can be easily obtained as an over-the-counter medication. There has been a growing number of reported cases of toxicity in recent years. Generally, there are numerous instances of mild symptoms, with only a limited number of reports of severe cases necessitating intensive care. We presented the case of a female who ingested 111 tablets of dextromethorphan, leading to shock and convulsions and requiring intensive care that ultimately saved her life. CASE SUMMARY: A 19-year-old female was admitted to our hospital via ambulance, having overdosed on 111 tablets of dextromethorphan (15 mg) obtained through an online importer in a suicide attempt. The patient had a history of drug abuse and multiple self-inflicted injuries. At the time of admission, she exhibited symptoms of shock and altered consciousness. However, upon arrival at the hospital, the patient experienced recurrent generalized clonic convulsions and status epilepticus, necessitating tracheal intubation. The convulsions were determined to have been caused by decreased cerebral perfusion pressure secondary to shock, and noradrenaline was administered as a vasopressor. Gastric lavage and activated charcoal were also administered after intubation. Through systemic management in the intensive care unit, the patient's condition stabilized, and the need for vasopressors ceased. The patient regained consciousness and was extubated. The patient was subsequently transferred to a psychiatric facility, as suicidal ideation persisted. CONCLUSION: We report the first case of shock caused by an overdose of dextromethorphan.

15.
Biomolecules ; 13(6)2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37371472

RESUMO

Asthma is a heterogeneous disease characterized by chronic airway inflammation. Group 2 innate lymphoid cells (ILC2) play an important role in the pathogenesis of asthma. ILC2s lack antigen-specific receptors and respond to epithelial-derived cytokines, leading to the induction of airway eosinophilic inflammation in an antigen-independent manner. Additionally, ILC2s might be involved in the mechanism of steroid resistance. Numerous studies in both mice and humans have shown that ILC2s induce airway inflammation through inflammatory signals, including cytokines and other mediators derived from immune or non-immune cells. ILC2s and T helper type 2 (Th2) cells collaborate through direct and indirect interactions to organize type 2 immune responses. Interestingly, the frequencies or numbers of ILC2 are increased in the blood and bronchoalveolar lavage fluid of asthma patients, and the numbers of ILC2s in the blood and sputum of severe asthmatics are significantly larger than those of mild asthmatics. These findings may contribute to the regulation of the immune response in asthma. This review article highlights our current understanding of the functional role of ILC2s in asthma.


Assuntos
Asma , Imunidade Inata , Humanos , Camundongos , Animais , Linfócitos , Citocinas , Inflamação
16.
Diagn Cytopathol ; 51(6): E199-E203, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36916714

RESUMO

Syphilis is a sexually transmitted infection that causes serious health problems without treatment. Detection of syphilis is necessary to stop the spread of the infection. Cytological screeners and pathologists may experience fine-needle aspiration cytology (FNAC) for syphilitic lymphadenitis; however, its characteristic cytological features are rarely reported. We present FNAC cytological features of syphilitic lymphadenitis in a case of a 21-year-old man. He presented with a sore throat and painful neck lymphadenopathy. His swollen and painful neck persisted even with antibiotic treatment. Necrotizing lymphadenitis and lymphoma were clinically suspected. FNAC was taken from the swollen lymph node. Cytologic findings of the specimen showed various inflammatory cells with small-sized vessels arranged in a branching/arborizing fashion. The vessels were surrounded by inflammatory cells, including plasma cells, neutrophils, and macrophages. Perivascular plasma cell cuffing was focally seen along with inconspicuous granulomas. Neutrophils appeared to involve the vascular wall. The cytological findings suggested syphilitic lymphadenitis, and clinical findings and serological tests confirmed primary syphilis with concomitant human immunodeficiency virus infection. Branching/arborizing vessels associated with many plasma cells, vascular involvement of neutrophils, and granulomas may suggest syphilitic infection if the specimen is obtained via FNAC. (189 words).


Assuntos
Linfadenite , Sífilis , Masculino , Humanos , Adulto Jovem , Adulto , Biópsia por Agulha Fina , Sífilis/diagnóstico , Sífilis/patologia , Sífilis/terapia , Linfadenite/patologia , Granuloma/patologia , Linfonodos/patologia
17.
FEBS Lett ; 597(8): 1164-1175, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36754848

RESUMO

Cholinergic receptor muscarinic 3 (CHRM3)-mediated focal adhesion kinase/YES-associated protein (YAP) signalling is essential for the growth of castration-resistant prostate cancer (CRPC) cells. Here, we evaluated the molecular mechanisms through which CHRM3 overexpression facilitates castration-resistant growth. Small RNA sequencing combined with in silico analyses revealed that CHRM3 was a putative target of miR-15b-5p. Notably, androgen deprivation suppressed miR-15b-5p expression and increased CHRM3 expression. Moreover, miR-15b-5p bound directly to CHRM3 and inhibited YAP activation induced by CHRM3 stimulation. Furthermore, miR-15b-5p abolished the growth of CRPC cells induced by CHRM3 stimulation. We conclude that the miR-15b-5p/CHRM3/YAP signalling axis promotes the castration-resistant growth of prostate cancer.


Assuntos
MicroRNAs , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios , Proliferação de Células/fisiologia , Castração , Linhagem Celular Tumoral , Receptores Colinérgicos/metabolismo , Colinérgicos , Regulação Neoplásica da Expressão Gênica , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo
18.
Adv Clin Chem ; 112: 155-204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36642483

RESUMO

Immune checkpoint inhibitors (ICI) are key drugs in systemic therapy for advanced non-small-cell lung cancer (NSCLC) and have recently been incorporated into neoadjuvant and adjuvant settings for surgical resection. Currently, ICI combinations with cytotoxic agents are frequently used in clinical practice, although several ICI clinical trials have failed to produce long-term clinical benefits. Unfortunately, clinical benefit is moderate and limited considering physical and financial burden. Therefore, selecting appropriate patients and regimens for ICI therapy is important, and biomarkers are necessary for their selection. Tumor PD-L1 expression is universally used as a biomarker; however, PD-L1 assays show low analytical validity and reproducibility due to the visual-scoring system by pathologists. Recent tumor immunology studies explore that neoantigens derived from somatic mutations and the collaboration between T and B cells efficiently elicit antitumor responses. This suggests that high tumor mutational burden and T-cell infiltration are predictive biomarkers. However, B cells producing antibody (Ab) remain poorly understood and analyzed as biomarkers. We found that NY-ESO-1 and XAGE1 of cancer-testis antigen frequently elicit spontaneous humoral and cellular immune responses in NSCLC. Serum Ab against these antigens were detected in approximately 25% of NSCLC patients and predicted ICI monotherapy responses. In addition, the Ab levels were decreased with tumor shrinkage after ICI therapy. Thus, NY-ESO-1 and XAGE1 Ab are potentially biomarkers predicting and monitoring response to ICI therapy. For clinical applications, a fully-automated assay system measuring the Ab was developed. Here, we review current ICI therapy, tumor immunology, and biomarkers in NSCLC, and discuss the applicability of the serum biomarkers NY-ESO-1 and XAGE1 Ab.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Masculino , Anticorpos , Antígenos de Neoplasias , Antígeno B7-H1 , Biomarcadores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Reprodutibilidade dos Testes , Inibidores de Checkpoint Imunológico/uso terapêutico
19.
J Eukaryot Microbiol ; 70(2): e12946, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36047902

RESUMO

Apusomonadida (apusomonads) is a group of heterotrophic biflagellates that feed on bacteria and small protists. Their diversity is not fully understood, and several major lineages remain to be identified in natural environments. Here, we report Podomonas kaiyoae n. sp., which was isolated from deep-sea sediment and can be maintained as an axenic culture. While P. kaiyoae branched within one of the major unidentified lineages, the combination of the morphological characteristics is generally similar to that of Podomonas species, but can be distinguished from that of other Podomonas species based on the cell sizes.


Assuntos
Eucariotos , Água do Mar , RNA Ribossômico 18S , Filogenia , Eucariotos/genética , Processos Heterotróficos , Análise de Sequência de DNA
20.
Mol Oncol ; 17(2): 328-343, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36345848

RESUMO

Small-cell lung cancer (SCLC) is associated with a high mortality rate and limited treatment efficacy. We created a microRNA (miRNA) expression signature by RNA sequencing using specimens from patients with SCLC who had failed treatment. Forty-nine miRNAs were downregulated in SCLC tissues and were candidate tumor-suppressive miRNAs. In this signature, both guide and passenger strands were downregulated for five miRNAs (miR-30a, miR-34b, miR-34c, miR-223, and miR-4529). Recent studies have revealed that passenger strands of miRNAs are involved in the molecular pathogenesis of human cancer. Although miR-30a-5p (the guide strand) has been shown to be a tumor-suppressive miRNA in various types of cancers, miR-30a-3p (the passenger strand) function is not well characterized in SCLC cells. We investigated the functional significance of miR-30a-3p and oncogenic genes regulated by miR-30a-3p in SCLC cells. Ectopic expression assays showed that miR-30a-3p expression inhibited cell proliferation and induced cell cycle arrest and apoptosis in two SCLC cell lines. Furthermore, in silico database searches and gene expression assays identified 25 genes as putative targets of miR-30a-3p in SCLC cells. Luciferase reporter assays revealed that downstream neighbor of SON (DONSON) was directly regulated by miR-30a-3p in SCLC cells. Knockdown of DONSON induced cell cycle arrest in SCLC cells and DONSON overexpression were detected in SCLC clinical samples. Analyzing the regulatory networks of tumor-suppressive miRNAs may lead to the identification of therapeutic targets in SCLC.


Assuntos
Neoplasias Pulmonares , MicroRNAs , Carcinoma de Pequenas Células do Pulmão , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Falha de Tratamento , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
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