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1.
Bioorg Med Chem Lett ; 113: 129947, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39245150

RESUMO

Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp. KTF-0504 strain. We revealed that 1 showed anti-malarial activity against Plasmodium falciparum parasite strains. On the other hands, 1 showed no anti-fungal activity against multidrug-sensitive budding yeast. Our study implies that the utilization of the laeA gene in fungi is a versatile method for the discovery of drug candidates.


Assuntos
Antimaláricos , Plasmodium falciparum , Antimaláricos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Metabolismo Secundário , Estrutura Molecular , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Testes de Sensibilidade Parasitária , Hypocreales/metabolismo , Hypocreales/química , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade
2.
Biochem Biophys Res Commun ; 728: 150345, 2024 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-38971001

RESUMO

The transfer of nitrogen fixation (nif) genes from diazotrophs to non-diazotrophic hosts is of increasing interest for engineering biological nitrogen fixation. A recombinant Escherichia coli strain expressing Azotobacter vinelandii 18 nif genes (nifHDKBUSVQENXYWZMF, nifiscA, and nafU) were previously constructed and showed nitrogenase activity. In the present study, we constructed several E. coli strain derivatives in which all or some of the 18 nif genes were additionally integrated into the fliK locus of the chromosome in various combinations. E. coli derivatives with the chromosomal integration of nifiscA, nifU, and nifS, which are involved in the biosynthesis of the [4Fe-4S] cluster of dinitrogenase reductase, exhibited enhanced nitrogenase activity. We also revealed that overexpression of E. coli fldA and ydbK, which encode flavodoxin and flavodoxin-reducing enzyme, respectively, enhanced nitrogenase activity, likely by facilitating electron transfer to dinitrogenase reductase. The additional expression of nifM, putatively involved in maturation of dinitrogenase reductase, further enhanced nitrogenase activity and the amount of soluble NifH. By combining these factors, we successfully improved nitrogenase activity 10-fold.


Assuntos
Azotobacter vinelandii , Escherichia coli , Fixação de Nitrogênio , Nitrogenase , Azotobacter vinelandii/genética , Azotobacter vinelandii/enzimologia , Azotobacter vinelandii/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Nitrogenase/metabolismo , Nitrogenase/genética , Fixação de Nitrogênio/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
3.
J Dermatol ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031284

RESUMO

Clinical trials of biologics have frequently excluded elderly patients, resulting in inadequate data on their safety and efficacy. Additionally, evidence of their safety and efficacy remains limited, despite some real-world studies. To assess the safety and efficacy of biologics in elderly patients with psoriasis, we compared these outcomes in younger patients using data from the West Japan Psoriasis Registry (WJPR). The WJPR consists of approximately 30 facilities in Western Japan, including various healthcare settings. This study enrolled 1395 patients who participated in the 2022 follow-up survey of the WJPR and were either using or had used biologics during the survey. These included 456 patients in the elderly group (≥65 years) and 939 patients in the younger group (<65 years). Treatment-ending adverse events (TEAEs) occurred in 15.8% and 11.3% of elderly and younger patients, respectively. The incidence rate per 1000 patient-years (PY) for TEAEs was significantly higher in elderly patients than in younger patients (32.9 vs 23.2, p = 0.0234). Infectious diseases were more prevalent in the elderly group than the younger group; however, no significant difference in the frequency of infectious diseases was found between the two groups (p = 0.0807). Malignant neoplasms occurred significantly more frequently in the elderly group than in the younger group (p = 0.0169). Our results indicate a few concerns about infection when prescribing biologics to elderly patients. Biologics were effective for both elderly and younger patients. We found no significant differences in the proportion of patients with a body surface area score ≤3%, Physician's Global Assessment score 0/1, or Patient's Global Assessment score 0/1, as well as in the mean Dermatology Life Quality Index and the Itch Numerical Rating Scale between the younger and the elderly groups. Overall, our results confirm the appropriateness of using biologics in elderly patients with regard to safety and efficacy.

4.
Sci Rep ; 14(1): 7699, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565866

RESUMO

Nasopalatine duct cysts are difficult to detect on panoramic radiographs due to obstructive shadows and are often overlooked. Therefore, sensitive detection using panoramic radiography is clinically important. This study aimed to create a trained model to detect nasopalatine duct cysts from panoramic radiographs in a graphical user interface-based environment. This study was conducted on panoramic radiographs and CT images of 115 patients with nasopalatine duct cysts. As controls, 230 age- and sex-matched patients without cysts were selected from the same database. The 345 pre-processed panoramic radiographs were divided into 216 training data sets, 54 validation data sets, and 75 test data sets. Deep learning was performed for 400 epochs using pretrained-LeNet and pretrained-VGG16 as the convolutional neural networks to classify the cysts. The deep learning system's accuracy, sensitivity, and specificity using LeNet and VGG16 were calculated. LeNet and VGG16 showed an accuracy rate of 85.3% and 88.0%, respectively. A simple deep learning method using a graphical user interface-based Windows machine was able to create a trained model to detect nasopalatine duct cysts from panoramic radiographs, and may be used to prevent such cysts being overlooked during imaging.


Assuntos
Cistos , Aprendizado Profundo , Humanos , Radiografia Panorâmica , Redes Neurais de Computação , Cistos/diagnóstico por imagem , Bases de Dados Factuais
5.
Clin J Gastroenterol ; 17(4): 671-676, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38642275

RESUMO

A 75-year-old man was referred to our department because of an enlarging intrahepatic mass detected on magnetic resonance imaging (MRI) follow-up for another disease. MRI showed hypointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging in liver segment 4. Abdominal plain computed tomography (CT) indicated a low-density lesion with an unclear boundary, measuring approximately 4 cm × 3 cm in liver segment 4. Dynamic CT showed early rim enhancement and gradual central enhancement. Contrast-enhanced CT also showed occlusion of the portal vein in segment 4. As the possibility of intrahepatic cholangiocarcinoma could not be excluded on imaging studies, we performed laparoscopic left medial sectionectomy. Histologically, the lesion showed diminished numbers of hepatocytes with increased collagen fibers compared with normal, with no patent portal vein. We considered this lesion a reactive lesion caused by collapse of the liver parenchyma owing to localized obstruction and loss of the portal vein. This lesion was pathologically diagnosed as portal biliopathy. We experienced an extremely rare case of intrahepatic mass-forming portal biliopathy that mimicked a hepatic tumor, which was diagnosed by laparoscopic resection. Portal biliopathy rarely forms intrahepatic mass lesions and must be distinguished from a malignant hepatic tumor.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Veia Porta , Humanos , Masculino , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/diagnóstico , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Diagnóstico Diferencial , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Tomografia Computadorizada por Raios X , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética
6.
Biosci Biotechnol Biochem ; 88(7): 824-829, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38664007

RESUMO

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillus sp. FKI-5362. Compound 1 was not effective against Candida albicans and the detailed anti-fungal activity of 1 remains unverified. After our anti-fungal activity screening, 1 was found to inhibit the growth of broad plant pathogenic fungal species belonging to the Ascomycota. It is noteworthy that 1 showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeA is useful for new anti-fungal drug discovery.


Assuntos
Descoberta de Drogas , Saccharomyces cerevisiae , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Descoberta de Drogas/métodos , Candida albicans/efeitos dos fármacos , Metabolismo Secundário , Fungicidas Industriais/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Testes de Sensibilidade Microbiana , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Aspergillus/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
7.
Surg Case Rep ; 10(1): 22, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38233726

RESUMO

BACKGROUND: Robotic pancreatectomy has been performed worldwide mainly using the da Vinci® Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Recently, because of the death of some patents related to the da Vinci® system, new surgical robot systems have been introduced that are characterized by unique technical refinements. In Japan, the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan) was approved for use in gastroenterological surgery in October 2022. Since then, we have attempted complicated procedures using this robot. In this report, we report our first experience performing spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein using this first Japanese domestic surgical robot. CASE PRESENTATION: The patient was a 58-year-old woman with a mass in the pancreatic tail identified during medical screening. Further examinations resulted in a diagnosis of a pancreatic neuroendocrine tumor. The patient consented to surgical resection, and we planned robotic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein, using the hinotori™. Five trocars, including one port for the assistant surgeon, were placed in the upper abdomen. The operating unit was rolled in from the patient's right side. The pivot position was set for each robotic arm, and this setting was specific to the hinotori™. The cockpit surgeon performed all surgical procedures, excluding port placement and pancreatic transection. There were no unrecoverable device errors during the operation. The operation time was 531 min, and blood loss was 192 ml. The postoperative course was uneventful. We were able to safely perform this highly complicated surgery for a pancreatic tumor using the first Japanese domestic surgical robot platform. CONCLUSIONS: The first Japanese domestic surgical robot platform, hinotori™, has different features from those of the da Vinci® and performed sufficiently as a surgical robot system in highly advanced pancreatic surgery.

8.
Oral Radiol ; 40(2): 219-225, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38060046

RESUMO

OBJECTIVES: Despite the difficulty in distinguishing between squamous cell carcinoma (SCC) and medication-related osteonecrosis of the jaw (MRONJ) on the basis of medical imaging examinations, the two conditions have completely different treatment methods and prognoses. Therefore, differentiation of SCC from MRONJ on imaging examinations is very important. This study aimed to distinguish SCC from MRONJ by performing texture analysis using magnetic resonance imaging (MRI) short-tau inversion recovery images. METHODS: This retrospective case-control study included 14 patients with SCC of the lower gingiva and 35 with MRONJ of the mandible who underwent MRI and computed tomography (CT) for suspected SCC or MRONJ. SCC was identified by histopathological examination of tissues excised during surgery. The radiomics features of SCC and MRONJ were analyzed using the open-access software MaZda version 3.3 (Technical University of Lodz, Institute of Electronics, Poland). CT was used to evaluate the presence or absence of qualitative findings (sclerosis, sequestrum, osteolysis, periosteal reaction, and cellulitis) of SCC and MRONJ. RESULTS: Among the 19 texture features selected using MaZda feature-reduction methods, SCC of the gingiva and MRONJ of the mandible revealed differences in two histogram features, one absolute gradient feature, and 16 Gy level co-occurrence matrix features. In particular, the percentile, angular second moment, entropy, and difference entropy exhibited excellent diagnostic performance. CONCLUSION: Non-contrast-enhanced MRI texture analysis revealed differences in texture parameters between mandibular SCC and mandibular MRONJ. MRI texture analysis can be a new noninvasive quantitative method for distinguishing between SCC and MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Carcinoma de Células Escamosas , Humanos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Estudos Retrospectivos , Estudos de Casos e Controles , Gengiva/patologia , Imageamento por Ressonância Magnética , Carcinoma de Células Escamosas/diagnóstico por imagem
9.
Clin J Gastroenterol ; 17(1): 143-147, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38085443

RESUMO

Anisakiasis is a parasitic infection caused by the ingestion of raw or undercooked seafood infected with Anisakis larvae. It generally affects the gastrointestinal tract, particularly the stomach, but very rare cases have been reported in which infection of the liver leads to the formation of inflammatory pseudotumors. We herein report an extremely rare case of an inflammatory pseudotumor induced by hepatic anisakiasis that was laparoscopically resected for the purpose of both diagnosis and treatment. A 51-year-old woman underwent a routine medical checkup by ultrasound examination, which incidentally detected a 15-mm mass on the surface of S6 of the liver. Because a malignant tumor could not be ruled out on several preoperative imaging studies, laparoscopic partial resection of the liver was performed. Histopathological examination revealed Anisakis larva in the inflammatory pseudotumor, suggesting hepatic anisakiasis. This report describes an extremely rare case of an inflammatory pseudotumor induced by hepatic anisakiasis. Because the preoperative diagnosis could not be obtained by several imaging modalities, laparoscopic liver resection with a sufficient margin might be suitable for diagnosis and treatment of this disease.


Assuntos
Anisaquíase , Anisakis , Granuloma de Células Plasmáticas , Animais , Feminino , Humanos , Pessoa de Meia-Idade , Anisaquíase/diagnóstico , Anisaquíase/cirurgia , Anisaquíase/parasitologia , Granuloma de Células Plasmáticas/diagnóstico por imagem , Granuloma de Células Plasmáticas/cirurgia , Estômago/patologia , Larva , Fígado/cirurgia , Fígado/patologia
10.
Surg Case Rep ; 9(1): 211, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38047972

RESUMO

BACKGROUND: Since indocyanine green (ICG) accumulates selectively in hepatocellular carcinoma (HCC) cells, it can be used to detect metastatic lesions. Lymph node metastasis of HCC is rarely observed, both simultaneously and metachronously. Therefore, it is sometimes difficult to identify metachronous lymph nodes during salvage surgery because of prior surgery. Herein, we report a case in which lymph node metastasis of HCC was successfully resected using an ICG navigation system. CASE PRESENTATION: The patient was a 62-year-old man who had undergone radical liver resection for HCC 8 years ago. During surveillance, contrast-enhanced computed tomography (CT) revealed a mass in the hepatic hilum. Various diagnostic modalities suggested that the patient had a solitary metastatic lymph node of HCC, and extirpation of the tumor was planned. Intraoperative ICG fluorescence imaging allowed surgeons to clearly identify the target lesion. Histopathologically, the tumor was confirmed to be a lymph node metastasis of HCC. The patient's postoperative course was uneventful, and he remains alive without recurrence 2 years after the second surgery. CONCLUSION: Intraoperative navigation surgery by ICG fluorescence imaging was useful for the safe resection of extrahepatic metastasis of HCC in a complicated situation.

11.
AMB Express ; 13(1): 137, 2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38044351

RESUMO

Enzymatic detection of citrulline, a potential biomarker for various diseases, is beneficial. However, determining citrulline levels requires expensive instrumental analyses and complicated colorimetric assays. Although L-amino acid oxidase/dehydrogenase is widely used to detect L-amino acids, an L-citrulline-specific oxidase/dehydrogenase has not been reported. Therefore, in this study, we aimed to develop an L-citrulline-specific enzyme by introducing a mutation into L-arginine oxidase (ArgOX) derived from Pseudomonas sp. TPU 7192 to provide a simple enzymatic L-citrulline detection system. The ratio of the oxidase activity against L-arginine to that against L-citrulline (Cit/Arg) was 1.2%, indicating that ArgOX could recognize L-citrulline as a substrate. In the dehydrogenase assay, the specific dehydrogenase activity towards L-arginine was considerably lower than the specific oxidase activity. However, the specific dehydrogenase activity towards L-citrulline was only slightly lower than the oxidase activity, resulting in improved substrate specificity with a Cit/Arg ratio of 49.5%. To enhance the substrate specificity of ArgOX, we performed site-directed mutagenesis using structure-based engineering. The 3D model structure indicated that E486 interacted with the L-arginine side chain. By introducing the E486 mutation, the specific dehydrogenase activity of ArgOX/E486Q for L-citrulline was 3.25 ± 0.50 U/mg, which was 3.8-fold higher than that of ArgOX. The Cit/Arg ratio of ArgOX/E486Q was 150%, which was higher than that of ArgOX. Using ArgOX/E486Q, linear relationships were observed within the range of 10-500 µM L-citrulline, demonstrating its suitability for detecting citrulline in human blood. Consequently, ArgOX/E486Q can be adapted as an enzymatic sensor in the dehydrogenase system.

12.
Cancer Metab ; 11(1): 25, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066600

RESUMO

BACKGROUND: A hypoxic environment often persists within solid tumors, including hepatocellular carcinoma (HCC). Hypoxia-inducible factor-1α (HIF-1α) can accelerate cancer malignancy by inducing hypoxia-dependent expression of various genes. Tumor hypoxia can also induce metabolic reprogramming of fatty acid (FA) metabolism, through which HIF-1α plays an essential role in diminishing fatty acid ß-oxidation (FAO) in hypoxic cancer cells. METHODS: We aimed to investigate potential new drug therapy options for targeting hypoxic cancer cells within HCC tumors, specifically through combining HIF-1α inhibition with palmitic acid (PA) + L-carnitine (LC) treatment to effectively induce apoptosis in hypoxic HCC cells. To test this hypothesis, in vitro and in vivo studies were performed. RESULTS: We first demonstrated that hypoxia-dependent apoptosis was induced by an overload of PA in two HCC cell lines (HepG2 and Hep3B) via excessive production of reactive oxygen species (ROS). Moreover, this observed PA-induced apoptosis was enhanced by HIF-1α knockdown (KD) in these cells under hypoxia. In addition, the combination of PA with FAO activator LC increased FAO activity and led to stronger cell death than PA alone in hypoxic HIF-1α KD cells, specifically through further ROS generation. To clarify the mechanism of hypoxia-induced FA metabolism reprogramming, expression levels of the genes encoding FAO enzymes CPT1A, ACSL1, MCAD, and LCAD, FA transporter CD36, and FA esterification enzymes DGAT and APGAT were analyzed using HIF-1α KD and scramble control (SC) cells. The results suggested that HIF-1α could repress mRNA expression of the FAO-related enzymes and CD36, while it upregulated FA esterification gene expression. This suggested a central role for HIF-1α in hypoxia-induced reprogramming of FA metabolism in HCC cells. Using a nude mouse model, PA administration was found to induce apoptosis from ROS overproduction in HIF-1α KD tumors compared with SC tumors. Additional LC treatment synergistically enhanced the PA-induced apoptosis in HIF-1α KD tumors. Finally, in vivo therapy composed of HIF-1α inhibitor YC-1 with PA + LC could induce ROS-mediated apoptosis in HepG2 tumors without significant toxicity. CONCLUSIONS: A combination therapy of YC-1 with PA + LC may be a unique anti-tumor therapy for targeting hypoxic HCC cells, specifically by ROS overproduction leading to forced FAO activation.

13.
Anticancer Res ; 43(11): 4887-4895, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37909947

RESUMO

BACKGROUND/AIM: P53 is the most frequently mutated tumor suppressor gene among all cancers. In human cancers, specific residues of p53 are mutated at a high frequency, and those mutations are known as hotspot mutations. Mutant p53 promotes tumor progression through the gain-of-function (GOF) mechanism. However, its biological characteristics, especially its metastatic potential, owing to different hotspot mutations in gastric cancer remain unclear. In the present study, we investigated the p53-depended metastatic phenotype. MATERIALS AND METHODS: This study examined the differences in the metastatic potential of wild-type, mutant-p53-R175H, and mutant-p53-R273H NUGC-4 gastric cancer cells in vitro and in vivo. RESULTS: NUGC-4-mutant-p53-R175H cells showed significant cell proliferation, healing and invasive abilities in proliferation, wound healing and invasion assay, respectively, compared to wild-type and mutant-p53-R273H cells. Both NUGC-4-mutant-p53 cell types expressed epithelial-mesenchymal transition (EMT)-related proteins. Furthermore, NUGC-4-mutant-p53-R175H cells showed less attachment to the extracellular matrix and greater expression of EMT-related proteins than NUGC-4-mutant-p53-R273H cells. Regarding the peritoneal dissemination model, NUCG-4-mutant-p53-R175H and NUCG-4-mutant-p53-R273H cells demonstrated less frequent formation of dissemination nodules than NUGC-4-empty cells. In contrast, liver metastases were more frequent and greater in number in NUCG3-mutant-p53-R175H than in the other cell lines. CONCLUSION: Our results suggest that differences in the p53 status, even in the hotspot mutation site, affect not only the characteristics of the cells but also the metastatic ability of gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Oncologia , Fenótipo , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética
14.
Surg Oncol ; 50: 101974, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37459677

RESUMO

BACKGROUND: Although robotic surgery has rapidly spread in pancreatectomy [1], the procedure is performed by the da Vinci™ Surgical System (Intuitive Surgical Inc., CA), the most common surgical robot in the world [2]. We herein present our first experience of robotic distal pancreatectomy using a new Japanese surgical robot named the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan). METHODS: A 68-year-old man who was found to have the mass lesion in the pancreatic tail in a medical examination. Investigations, including various imaging studies suggested a diagnosis of pancreatic cancer (Fig. 1). The patient was considered for robotic pancreatectomy. RESULTS: Five trocars, including one port for the assistant surgeon, were placed at the upper abdomen. The operation unit was rolled in from the right side (Fig. 2). The patient successfully underwent robotic distal pancreatectomy combined with dissection of the regional lymph nodes using the hinotori™ system. The cockpit surgeon performed all procedures, excluding port placement, vessel clipping, and transection of the pancreas. There were no unrecoverable device errors in this operation. The total operation time was 473 minutes, and the estimated blood loss was 182 ml. The postoperative course was uneventful, and hospital length of stay was 10 days. Pathological diagnosis was pancreatic cancer, T1N1M0, Stage ⅡB. Adjuvant chemotherapy using S-1 was administered, and he has survived without recurrence for 3 months after the curative resection. CONCLUSIONS: This is the first report of robotic pancreatectomy using the hinotori™ system, which showed the favorable perioperative results. The accumulation of experience and further studies are required to confirm its clinical benefits.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Robótica , Masculino , Humanos , Idoso , Procedimentos Cirúrgicos Robóticos/métodos , Pancreatectomia/métodos , Pâncreas/cirurgia , Neoplasias Pancreáticas/cirurgia , Laparoscopia/métodos , Neoplasias Pancreáticas
15.
Int J Mol Sci ; 24(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37511305

RESUMO

Inflammatory processes play major roles in carcinogenesis and the progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But, there are no therapies for NASH-related HCC, especially focusing on these critical steps. Previous studies have reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In hepatoblastoma and HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed the expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed the expression of phosphorylated nuclear factor-κB and transforming growth factor-ß. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high-fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Carcinoma Hepatocelular/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Farnesiltranstransferase , Interleucina-6 , Subunidade alfa do Fator 1 Induzível por Hipóxia , Inibidores Enzimáticos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Linhagem Celular Tumoral
16.
J Dermatol ; 50(6): 753-765, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36786158

RESUMO

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA.


Assuntos
Artrite Psoriásica , Produtos Biológicos , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Estudos Retrospectivos , Taxa de Sobrevida , Japão/epidemiologia , Psoríase/tratamento farmacológico , Psoríase/diagnóstico , Produtos Biológicos/uso terapêutico , Ciclosporina/uso terapêutico , Sistema de Registros
17.
J Dermatol ; 50(6): 746-752, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36694440

RESUMO

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.


Assuntos
Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/genética , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/genética , Anamnese , Japão/epidemiologia
18.
Dentomaxillofac Radiol ; 52(3): 20220321, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36594821

RESUMO

OBJECTIVES: The aim of this study was to assess whether magnetic resonance imaging (MRI) texture features of the lateral pterygoid muscle can distinguish between rheumatoid arthritis (RA) and osteoarthritis (OA) of the temporomandibular joint (TMJ). METHODS: The authors extracted 279 texture features from 36 patients with RA and OA from the region of interest set for the lateral pterygoid muscle on short tau inversion recovery (STIR) images using MaZda Ver.3.3. A total of 10 texture features were selected using Fisher's coefficients, as well as probability of error and average correlation coefficients. Data observed to have a non-normal distribution using the Kolmogorov-Smirnov test were compared using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves were used to assess the ability of the 10 texture features to distinguish RA and OA of the TMJ. RESULTS: A total of 10 features (5 Correlation, 3 Run Length Nonuniformity, 1 Sigma, and 1 Teta) were selected from 279 texture features. These texture features revealed significant differences between the RA and OA groups (p < 0.01). The sensitivity, specificity, accuracy, and area under the ROC curve of the texture features for distinguishing RA from OA were 0.78-0.94, 0.89-1.0, 0.86-0.92, and 0.89-0.95, respectively. CONCLUSION: MRI texture analysis of the lateral pterygoid muscle may be useful for distinguishing between RA and OA of the TMJ.


Assuntos
Artrite Reumatoide , Osteoartrite , Transtornos da Articulação Temporomandibular , Humanos , Músculos Pterigoides/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia , Articulação Temporomandibular , Imageamento por Ressonância Magnética/métodos , Artrite Reumatoide/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem
19.
Magn Reson Med Sci ; 22(3): 283-288, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35283395

RESUMO

PURPOSE: Chronic diffuse sclerosing osteomyelitis (CDSO) is a non-suppurative inflammatory bone disease diagnosed based on combined clinical, histopathological, and radiological findings. Accurate diagnosis is important since CDSO is more refractory to treatment than suppurative osteomyelitis. The purpose of this study was to determine the diagnostic efficacy of diffusion-weighted imaging (DWI) in the quantitative assessment of CDSO to distinguish it from acute suppurative osteomyelitis (ASO) and chronic suppurative osteomyelitis (CSO) of the mandible. METHODS: Using a retrospective cohort study design, we analyzed MRI data of 6 patients with CDSO and 34 patients with ASO and CSO. The mean apparent diffusion coefficient (ADC) values of the three groups (CDSO, ASO, and CSO groups) were calculated, and differences were analyzed using Kruskal-Wallis and post-hoc Mann-Whitney tests with Bonferroni adjustments. We performed a receiver operating characteristic (ROC) curve analysis to evaluate the ability of the ADC to predict CDSO. P < 0.05 was considered statistically significant. RESULTS: The mean ADCs in the CDSO, ASO, and CSO groups were 1.22 ± 0.04 × 10-3 mm2/s, 1.28 ± 0.08 × 10-3 mm2/s, and 1.06 ± 0.09 × 10-3 mm2/s, respectively. Significant differences were observed between the ASO and CSO groups (P < 0.001) and CSO and CDSO groups (P < 0.01). However, there was no significant difference between the ASO and CDSO groups (P = 0.21). The ROC analysis revealed a cut-off ADC value of 1.19 for distinguishing the CSO group from the CDSO group. Sensitivity, specificity, accuracy, and area under the ROC curve were 1.0, 0.92, 0, 95, and 0.94, respectively. CONCLUSION: The results suggest that ADC may be useful in distinguishing CDSO from mandibular suppurative osteomyelitis.


Assuntos
Imagem de Difusão por Ressonância Magnética , Osteomielite , Humanos , Sensibilidade e Especificidade , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Osteomielite/diagnóstico por imagem , Curva ROC , Diagnóstico Diferencial , Mandíbula
20.
Oral Radiol ; 39(1): 75-82, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35303210

RESUMO

OBJECTIVES: This study aimed to quantitatively assess maxillary central incisor roots using pre-orthodontics computed tomography (CT) texture analysis as part of a radiomics quantitative analysis. METHODS: This retrospective case-control study included 16 patients with external apical root resorption (EARR) and 16 age- and sex-matched patients without EARR, after orthodontic treatment who underwent pre-orthodontics CT for jaw deformities. All patients were treated with a fixed orthodontic appliance before and after surgical orthodontic treatment. EARR was defined as root resorption ≥ 2 mm of the left and right maxillary central incisors on CT images more than 2 years after the start of orthodontic treatment. Texture features of the maxillary central incisor with and without EARR after orthodontic treatment were analyzed using the open-access software, MaZda Ver. 3.3. Ten texture features were selected using the Fisher method in MaZda from 279 original parameters, which were calculated for each of the maxillary central incisors with and without EARR. The results were tested using the Student's t test, Welch's t test, or Mann-Whitney U test. RESULTS: Four gray-level run length matrix features and six gray-level co-occurrence matrix features displayed significant differences between both the groups (p < 0.01). CONCLUSIONS: CT texture analysis was able to quantitatively assess maxillary central incisor roots and distinguish between maxillary central incisor roots with and without EARR. CT texture analysis may be a useful method for predicting EARR after orthodontic treatment.


Assuntos
Reabsorção da Raiz , Humanos , Reabsorção da Raiz/diagnóstico por imagem , Reabsorção da Raiz/etiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Tomografia Computadorizada por Raios X , Medição de Risco , Tomografia
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