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1.
Sci Rep ; 14(1): 9029, 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641657

RESUMEN

Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens. C16 suppressed the proliferation of CRC cells. Gene Ontology (GO) analysis revealed that the cell cycle-related GO category was substantially enriched in CRC cells treated with C16. C16 treatment resulted in G1 arrest and increased p21 protein and mRNA expression. Moreover, p21 expression was associated with CRC development as observed using immunohistochemical analysis of human CRC tissues. C16 upregulates p21 expression in CRC cells to regulate cell cycle and suppress tumor growth. Thus, PKR inhibitors may serve as a new treatment option for patients with CRC.


Asunto(s)
Neoplasias Colorrectales , Inhibidores de Proteínas Quinasas , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Ciclo Celular , Proliferación Celular , División Celular , Línea Celular Tumoral , Apoptosis , Regulación Neoplásica de la Expresión Génica
2.
Cureus ; 16(3): e55912, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38601382

RESUMEN

BACKGROUND: Constipation is a common gastrointestinal symptom in patients with ulcerative colitis (UC). Several studies on the general population have demonstrated a link between allergic diseases and constipation. However, evidence regarding the association between allergic diseases and constipation in UC is limited. This study aims to evaluate this issue in Japanese patients with UC. METHODS: This cross-sectional study recruited consecutive 387 patients with UC. We used a self-administered questionnaire to estimate the prevalence of physician-diagnosed allergic diseases. The definition of constipation was based on Rome I criteria and/or medication for constipation. RESULTS: The prevalence of constipation was 12.5%. The prevalence rates of asthma, atopic dermatitis, pollen allergy, food allergy, and drug allergy were 11.8%, 9.0%, 36.3%, 6.2%, and 8.3%, respectively. Allergic diseases were not associated with constipation (adjusted odds ratio [OR] with asthma (adjusted OR 0.98 [95% confidence interval [CI] 0.27-2.80]), atopic dermatitis (adjusted OR 0.67 [95% CI 0.10-2.56]), pollen allergy (adjusted OR 0.92 [95% CI 0.41-1.97]), food allergy (adjusted OR 0.76 [95% CI 0.11-2.95]), and drug allergy (adjusted OR 1.06 [95% CI 0.28-3.24]). Additionally, the number of allergic diseases was not associated with the prevalence of constipation. CONCLUSIONS: In Japanese UC patients, no association between allergic diseases and constipation was found.

3.
Int J Impot Res ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589515

RESUMEN

The association between ulcerative colitis (UC) and erectile dysfunction (ED) has been previously reported. Numerous previous studies have also reported an association between gastrointestinal symptoms and ED. Constipation and diarrhea are common in patients with UC. However, the specific association between bowel movement frequency and ED remains unclear. The aim of this study is to investigate the association between bowel movement frequency and ED in 164 patients with UC. The definition of ED, moderate to severe ED, and severe ED was the Sexual Health Inventory for Men score <22, <12, and <8, respectively. Bowel movement frequency was divided into three categories: (1) high (More than once a day), (2) normal (once a day, reference), and low (less than one time/day). The definition of constipation was based on the Rome I criteria and/or medication for constipation. The prevalence of constipation and ED was 10.4% and 86.0%, respectively. The rate of high, normal, and low bowel movement frequency was 56.1%, 25.0%, and 18.9%, respectively. High bowel movement frequency was independently and positively associated with ED and moderate to severe ED (ED: adjusted odds ratio [OR] 4.42, 95% confidence interval [CI] 1.35-15.98; moderate to severe: adjusted OR 2.98, 95% CI 1.22-7.61). Low bowel movement frequency was independently and positively associated with moderate to severe ED and severe ED (moderate to severe: adjusted OR 3.96, 95% CI 1.27-13.08; severe: adjusted OR 3.20, 95% CI 1.08-9.86). No association between constipation and ED was found. In conclusion, in Japanese patients with UC, both high and low bowel movement frequency were independently and positively associated with ED.

4.
Clin Neurol Neurosurg ; 240: 108261, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38599043

RESUMEN

This report presents a case of Alexander disease showing clinical characteristics mimicking progressive supranuclear palsy (PSP). A 67-year-old woman complaining of motor disturbance exhibited severe atrophy of medulla, spinal cord, and midbrain tegmentum, as well as periventricular hyperintensity on cerebral MRI. Genetic analysis identified a novel in-frame deletion/insertion mutation in the exon 3 of the GFAP gene. Interestingly, neurological findings and decreased striatal uptake in dopamine transporter SPECT were suggestive of PSP. A novel GFAP gene mutation found in the present case may cause the unique clinical phenotype, which should be differentiated from PSP.

5.
J Neurogastroenterol Motil ; 30(2): 229-235, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38576372

RESUMEN

Background/Aims: Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people. Methods: A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire. Results: The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018). Conclusion: Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.

6.
Clin J Gastroenterol ; 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38460085

RESUMEN

Pancreas divisum (PD) represents a prevalent congenital pancreatic variant, typically arising from the failure of fusion between the ventral and dorsal pancreatic ducts. This condition is frequently associated with recurrent pancreatitis. We herein present a case involving an incomplete PD diagnosis following the identification of a refractory postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (DP) for pancreatic cancer. A 74-year-old female patient, who had undergone laparoscopic DP for pancreatic cancer, developed a POPF accompanied by intraabdominal bleeding, necessitating urgent intervention radiology to avert life-threatening complications. Following this, intraabdominal drainage was performed through an intraoperative drainage root. Subsequent fistulography and endoscopic retrograde pancreatography unveiled the presence of an incomplete PD for the first time. Consequently, a stent was placed in the Santorini duct. However, the volume of pancreatic juice from the intraabdominal drainage tube exhibited no reduction. Despite repeated attempts to access the pancreatic duct via a guidewire through the drainage tube, these endeavors proved futile. Paradoxically, the removal of the external drainage tube led to a recurrence of intraabdominal abscess formation. Consequently, reinsertion of the drainage tube became imperative. Consideration was given to draining the abscess under endoscopic ultrasonography and performing pancreatic duct drainage. However, due to the diminution of the abscess cavity through the external fistula drainage procedure, coupled with the absence of pancreatic duct dilation and its tortuous course, it was deemed a formidable challenge. the patient necessitated a lifestyle adaptation with a permanently placed percutaneous drainage tube.

7.
Diabetes Metab J ; 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38310878

RESUMEN

Background: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%. Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. Conclusion: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

8.
Neurosci Lett ; 822: 137642, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38228218

RESUMEN

Multiple system atrophy (MSA) is a progressive and sporadic neurodegenerative disorder characterized by the histological appearance of glial cytoplasmic inclusions primarily composed of α-synuclein. Recently, complement-mediated neuroinflammation has been proposed as a key factor in the pathogenesis of numerous neurodegenerative disorders. We conducted immunohistochemical/immunofluorescent assays targeting a number of complements to explore the role of complements in MSA pathogenesis using brain samples from deceased patients and controls. Complement deposition was notably increased in the cerebral vasculature and myelin sheath in the MSA brains. Furthermore, fibrinogen leakage resulting from the disruption of the blood-brain barrier (BBB) was observed, along with the presence of C1q-positive microglia clusters surrounding the MSA brain vessels. These immunohistochemical/immunofluorescent findings suggest that complement activation and BBB disruption play critical roles in MSA progression.


Asunto(s)
Atrofia de Múltiples Sistemas , Humanos , Atrofia de Múltiples Sistemas/patología , Barrera Hematoencefálica/metabolismo , alfa-Sinucleína/metabolismo , Encéfalo/metabolismo , Microglía/metabolismo , Activación de Complemento
9.
Int J Urol ; 31(2): 154-159, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37861245

RESUMEN

OBJECTIVE: Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC. METHODS: One hundred and thirty-six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self-administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self-administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C-reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression. RESULTS: The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03-7.48, p for trend =0.044). No association between other marker and ED was found. CONCLUSION: Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC patients.


Asunto(s)
Colitis Ulcerosa , Disfunción Eréctil , Masculino , Humanos , Disfunción Eréctil/diagnóstico , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Estudios Transversales , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Encuestas y Cuestionarios , Albúmina Sérica
10.
J Gastroenterol Hepatol ; 39(3): 512-518, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38073066

RESUMEN

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.


Asunto(s)
Café , Colitis Ulcerosa , Humanos , Cafeína/efectos adversos , Cafeína/análisis , Japón/epidemiología , Estudios de Casos y Controles , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/etiología , Colitis Ulcerosa/prevención & control , Factores de Riesgo , Té/efectos adversos
12.
Gerontol Geriatr Med ; 9: 23337214231215637, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38035264

RESUMEN

Aim: Age is a risk factor for constipation. Constipation is common in patients with ulcerative colitis (UC) and has been positively associated with disease activity, but evidence is limited. This study aimed to assess the association between disease activity and constipation in patients with UC. Methods: The study subjects consisted of 290 Japanese UC patients. The definition of constipation was based on Rome I criteria and/or medication for constipation. Information on and lifestyle habits was obtained from a self-administered questionnaire. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0. Clinical remission (CR) was defined as both the absence of rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The prevalence of constipation is not associated with MH, CR, duration of UC and disease extent of UC. The prevalence of constipation among age groups, <40, 40-49 years, 50-59 years, 60-69 years, and >70 years was 10.0%, 5.8%, 15.7%, 11.8%, and 25.6%, respectively. >70 years was independently and positively associated with the prevalence of constipation (adjusted odds ratio 3.64 [95% confidence interval 1.26, 10.95], p for trend: .001). Conclusions: Aging was independently and positively associated with the prevalence of constipation in UC.

13.
J Alzheimers Dis ; 96(4): 1623-1638, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38007650

RESUMEN

BACKGROUND: The cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 217 (p217tau) or 181 (p181tau), and neurofilament light chain (NfL) are definite biomarkers of tauopathy and neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: To validate their utility in excluding other neurological diseases and age-related changes in clinical settings. METHODS: We developed monoclonal antibodies against p217tau and NfL, established novel ELISAs, and analyzed 170 CSF samples from patients with AD or other neurological diseases. RESULTS: In AD, p217tau is a more specific and abundant CSF component than p181tau. However, CSF NfL levels increase age-dependently and to a greater extent in central and peripheral nervous diseases than in AD. CONCLUSIONS: CSF p217tau correlates better with AD neurodegeneration than other tau-related biomarkers and the major phosphorylated tau species. The clinical usage of NfL as a neurodegeneration biomarker in AD requires exclusion of various central and peripheral neurological diseases.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Filamentos Intermedios , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo
14.
Dig Dis ; 41(6): 845-851, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37708872

RESUMEN

INTRODUCTION: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. METHODS: Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. RESULTS: The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27-2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. CONCLUSION: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.


Asunto(s)
Síndrome del Colon Irritable , Humanos , Femenino , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/epidemiología , Estudios Transversales , Prevalencia , Japón/epidemiología , Dismenorrea/complicaciones
15.
Urology ; 181: 119-123, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37579856

RESUMEN

OBJECTIVE: To investigate the association between nocturia and constipation in patients with ulcerative colitis (UC). Constipation has recently been recognized as an important symptom in patients with UC. Although nocturia has been associated with constipation in the general population, the association between nocturia and constipation in UC patients is uncertain. METHODS: Consecutive series of 290 Japanese patients with UC, Information on constipation, nocturia, and lifestyle habits was obtained using self-administered questionnaires. The definition of constipation was based on Rome I criteria and/or current medication for constipation. Patients were divided into three groups based on nighttime urination: (1) no nocturia, (2) mild nocturia (nocturnal urination - one), and (3) serious nocturia (nocturnal urination - two or more). Multivariate logistic regression was used to evaluate the association between nocturia and constipation. RESULTS: Among all of the UC patients, the prevalence of mild nocturia, serious nocturia, and constipation was 35.2%, 26.9%, and 12.4%, respectively. The prevalence of constipation in the none, mild, and serious nocturia groups was 8.2%, 10.8%, and 20.5%, respectively. After adjustment for confounders such as age, sex, current drinking, current smoking, body mass index, and steroid use, nocturia severity was independently and positively associated with constipation (adjusted odds ratio for mild nocturia: 1.55 [95% confidence interval: 0.57-4.28], serious nocturia: 3.19 [95% confidence interval: 1.09-9.81], P for trend=.035). CONCLUSION: The severity of nocturia is positively associated with constipation, and physicians should consider the interrelationships between nocturia and constipation in managing UC patients.


Asunto(s)
Colitis Ulcerosa , Nocturia , Humanos , Colitis Ulcerosa/complicaciones , Nocturia/epidemiología , Nocturia/etiología , Índice de Masa Corporal , Estreñimiento/complicaciones , Estreñimiento/epidemiología , Estilo de Vida
16.
J Neurol Sci ; 451: 120713, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37441875

RESUMEN

123I-ioflupane single-photon emission computed tomography (SPECT) is a highly sensitive and established neuroimaging technique for parkinsonian syndromes (PS). However, differentiating PS by visual inspection or analysis of regions of interest is challenging. To date, image analysis has not been able to differentiate dementia with Lewy bodies (DLB) from Parkinson's disease with dementia (PDD). This study aimed to differentiate PS based on the characteristics of striatal dopamine transporter (DAT) binding using voxel-based analysis. We acquired 123I-ioflupane SPECT data from patients with DLB (n = 30), Parkinson's disease (PD; n = 122), PDD (n = 19), multiple system atrophy with predominant parkinsonism (MSA-P; n = 18), and progressive supranuclear palsy (PSP; n = 45). DAT binding was reduced in the posterior striatum of patients with PD and PDD, whereas it was similar in MSA-P, PSP, and DLB. Hippocampal atrophy, visually evaluated by cerebral magnetic resonance imaging, did not affect striatal DAT binding in DLB. DAT binding in the anterior striatum was inversely correlated with the severity of parkinsonism in PD and PDD but not in DLB. Thus, the appearance of striatal DAT binding might indicate different pathological processes in DLB and PDD.


Asunto(s)
Enfermedad por Cuerpos de Lewy , Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Trastornos Parkinsonianos , Humanos , Enfermedad de Parkinson/metabolismo , Enfermedad por Cuerpos de Lewy/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos
17.
J Neurol Neurosurg Psychiatry ; 94(10): 816-824, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37142397

RESUMEN

BACKGROUND: Several genetic factors are associated with the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) and its phenotypes, such as disease progression. Here, in this study, we aimed to identify the genes that affect the survival of patients with sporadic ALS. METHODS: We enrolled 1076 Japanese patients with sporadic ALS with imputed genotype data of 7 908 526 variants. We used Cox proportional hazards regression analysis with an additive model adjusted for sex, age at onset and the first two principal components calculated from genotyped data to conduct a genome-wide association study. We further analysed messenger RNA (mRNA) and phenotype expression in motor neurons derived from induced pluripotent stem cells (iPSC-MNs) of patients with ALS. RESULTS: Three novel loci were significantly associated with the survival of patients with sporadic ALS-FGF1 at 5q31.3 (rs11738209, HR=2.36 (95% CI, 1.77 to 3.15), p=4.85×10-9), THSD7A at 7p21.3 (rs2354952, 1.38 (95% CI, 1.24 to 1.55), p=1.61×10-8) and LRP1 at 12q13.3 (rs60565245, 2.18 (95% CI, 1.66 to 2.86), p=2.35×10-8). FGF1 and THSD7A variants were associated with decreased mRNA expression of each gene in iPSC-MNs and reduced in vitro survival of iPSC-MNs obtained from patients with ALS. The iPSC-MN in vitro survival was reduced when the expression of FGF1 and THSD7A was partially disrupted. The rs60565245 was not associated with LRP1 mRNA expression. CONCLUSIONS: We identified three loci associated with the survival of patients with sporadic ALS, decreased mRNA expression of FGF1 and THSD7A and the viability of iPSC-MNs from patients. The iPSC-MN model reflects the association between patient prognosis and genotype and can contribute to target screening and validation for therapeutic intervention.


Asunto(s)
Esclerosis Amiotrófica Lateral , Células Madre Pluripotentes Inducidas , Humanos , Esclerosis Amiotrófica Lateral/patología , Células Madre Pluripotentes Inducidas/metabolismo , Estudio de Asociación del Genoma Completo , Pueblos del Este de Asia , Factor 1 de Crecimiento de Fibroblastos/genética , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Neuronas Motoras/patología
18.
World J Gastroenterol ; 29(17): 2657-2665, 2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37213405

RESUMEN

BACKGROUND: Mucosal patterns (MPs) observed on blue laser imaging in patients with atrophic gastritis can be classified as spotty, cracked, and mottled. Furthermore, we hypothesized that the spotty pattern may change to the cracked pattern after Helicobacter pylori (H. pylori) eradication. AIM: To further substantiate and comprehensively investigate MP changes after H. pylori eradication in a larger number of patients. METHODS: We included 768 patients who were diagnosed with atrophic gastritis with evaluable MP using upper gastrointestinal endoscopy at the Nishikawa Gas-trointestinal Clinic, Japan. Among them, 325 patients were H. pylori-positive, and of them, 101 patients who underwent upper gastrointestinal endoscopy before and after H. pylori eradication were evaluated for post-eradication MP changes. The patients' MPs were interpreted by three experienced endoscopists who were blinded to their clinical features. RESULTS: Among 76 patients with the spotty pattern before or after H. pylori eradication, the pattern disappeared or decreased in 67 patients [88.2%, 95% confidence interval (CI): 79.0%-93.6%), appeared or increased in 8 patients (10.5%, 95%CI: 5.4%-19.4%), and showed no change in 1 patient (1.3%, 95%CI: 0.2%-7.1%). In 90 patients with the cracked pattern before or after H. pylori eradication, the pattern disappeared or decreased in 7 patients (7.8%, 95%CI: 3.8%-15.2%), appeared or increased in 79 patients (87.8%, 95%CI: 79.4%-93.0%), and showed no change in 4 patients (4.4%, 95%CI: 1.7%-10.9%). In 70 patients with the mottled pattern before or after H. pylori eradication, the pattern disappeared or decreased in 28 patients (40.0%, 95%CI: 29.3%-51.7%), appeared or increased in 35 patients (50.0%, 95%CI: 38.6%-61.4%), and showed no change in 7 patients (10.0%, 95%CI: 4.9%-19.2%). CONCLUSION: After H. pylori eradication, MPs changed from spotty to cracked in most patients, which may help endoscopists easily and precisely evaluate H. pylori-related gastritis status.


Asunto(s)
Gastritis Atrófica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Gastritis Atrófica/diagnóstico por imagen , Mucosa Gástrica/diagnóstico por imagen , Gastritis/diagnóstico por imagen , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/diagnóstico por imagen , Infecciones por Helicobacter/tratamiento farmacológico , Rayos Láser
19.
Hepatol Res ; 53(9): 806-814, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37183992

RESUMEN

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

20.
Sex Med ; 11(2): qfad024, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37256220

RESUMEN

Background: The association between disease activity and erectile dysfunction (ED) in patients with inflammatory bowel disease (IBD) is inconsistent, although IBD, including ulcerative colitis (UC), is reported as a risk factor for ED. Aim: The purpose of this study was to explore this association in Japanese patients with UC. Methods: In this study, we enrolled 165 Japanese male patients with UC. Information regarding the Sexual Health Inventory for Men (SHIM) score, medication, and severity of UC was obtained from medical records, self-administered questionnaires, and reports from physicians. The definition of ED and severe ED is a SHIM score <17 and <8, respectively. Outcomes: No association between severity of UC and ED was found in Japanese patients. Aging is independently positively associated with ED in patients with UC. Results: The prevalence of severe ED and ED was 47.9% and 64.9%, respectively. In this study, mucosal healing, clinical remission, duration of UC, disease extent, and medication were not associated with the prevalence of ED. Older age (≥63 years of age) was independently positively associated with ED (adjusted odds ratio, 12.93; 95% CI: 4.51-43.00) and severe ED (adjusted odds ratio, 9.02; 95% CI: 3.66-23.91). Clinical Implications: Disease severity of UC might not be associated with the prevalence of ED in patients with UC. Strengths and Limitations: This is the first study to investigate the association between several factors regarding UC activity and ED. The limitation of this study is the definition of ED based on SHIM scores. Conclusion: No association between severity of UC and ED was found in Japanese patients. As expected, aging may be independently positively associated with ED in patients with UC.

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