RESUMEN
OBJECTIVES: We report a case of bacteremia with pyelonephritis in an adult male with an underlying disease caused by α-hemolytic streptococci. α-Hemolytic streptococci were isolated from blood, but it was challenging to identify its species. This study aimed to characterize the causative bacterium SP4011 and to elucidate its species. METHODS: The whole-genome sequence and biochemical characteristics of SP4011 were determined. Based on the genome sequence, phylogenetic analysis was performed with standard strains of each species of α-hemolytic streptococci. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values were calculated. RESULTS: SP4011 showed optochin susceptibility and bile solubility, but did not react with pneumococcal omni antiserum. Phylogenetic analysis of the whole-genome sequence showed that SP4011 clustered with S. pneumoniae and S. pseodopneumoniae and was most closely related to S. pseodopneumoniae. Genomic analysis revealed that ANI and dDDH values between SP4011 and S. pseodopneumoniae were 94.0 % and 56.0 %, respectively, and between SP4011 and S. pneumoniae were 93.3 % and 52.2 %, respectively. Biochemical characteristics also showed differences between SP4011 and S. pseodopneumoniae and between SP4011 and S. pneumoniae. These results indicate that SP4011 is a novel species. CONCLUSION: Our findings indicate that SP4011 is a novel species of the genus Streptococcus. SP4011 has biochemical characteristics similar to S. pneumoniae, making it challenging to differentiate and requiring careful clinical diagnosis. This isolate was proposed to be a novel species, Streptococcus parapneumoniae sp. nov. The strain type is SP4011T (= JCM 36068T = KCTC 21228T).
Asunto(s)
Bacteriemia , Filogenia , Pielonefritis , Infecciones Estreptocócicas , Streptococcus , Humanos , Masculino , Infecciones Estreptocócicas/microbiología , Bacteriemia/microbiología , Streptococcus/genética , Streptococcus/aislamiento & purificación , Streptococcus/clasificación , Pielonefritis/microbiología , Genoma Bacteriano , ADN Bacteriano/genética , Secuenciación Completa del Genoma , Antibacterianos/farmacología , Hibridación de Ácido Nucleico , Técnicas de Tipificación Bacteriana , Pruebas de Sensibilidad Microbiana , Persona de Mediana EdadRESUMEN
Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50 s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria.
RESUMEN
Purpose: The pathophysiology of penis extends to erectile dysfunction (ED) to conditions including sexually transmitted diseases (STDs) and cancer. To date, there has been little research evaluating vascular drainage from the penis. We aimed to evaluate penile blood flow in vivo and analyze its possible relationship with the lymphatic maker. Materials and Methods: We established an in vivo system designed to assess the dynamic blood outflow from the corpus cavernosum (CC) by dye injection. To analyze lymphatic characteristics in the CC, the expression of Lyve-1, the key lymphatic endothelium marker, was examined by the in vitro system and lipopolysaccharide (LPS) injection to mimic the inflammatory conditions. Results: A novel cavernography methods enable high-resolution morphological and functional blood drainage analysis. The expression of Lyve-1 was detected along the sinusoids. Furthermore, its prominent expression was also observed after penile LPS injection and in the erectile condition. Conclusions: The current in vivo system will potentially contribute to the assessment of penile pathology from a novel viewpoint. In addition, current analyses revealed inducible Lyve-1 expression for LPS injection and the erection state, which requires further analyses on penile lymphatic system.
RESUMEN
IGLL5 is shown to be located near super-enhancer (SE) in B-cell tumors, and this gene is frequently mutated and a target of translocation in B-cell tumors. These results suggest roles of the IGLL5 in tumorigenesis; however, its functional properties have been unclear. We found that two mature B-cell lymphoma cell lines expressed IGLL5 mRNA with Cλ1 segment. JQ1 treatment resulted in down-expression of IGLL5, indicating that IGLL5 is controlled by SE. IGLL5 knockdown induced cell death with down-expression of MYC. Our results suggested that IGLL5 might have a role in survival of mature B-cell tumors and involvement in MYC expression. (100 words).
RESUMEN
A 75-year-old male with diabetes mellitus was referred to our hospital with an abnormal shadow on chest radiography, based on which he was diagnosed with extensive-disease small-cell lung cancer (ED-SCLC; cT2bN2M1a). The first-line therapy comprised atezolizumab, carboplatin, and etoposide. After four cycles, the patient achieved complete response (CR), and maintenance therapy was initiated with atezolizumab. However, even though CR was maintained, maintenance therapy was discontinued after 16 cycles due to persistent grade 2 anorexia and fatigue. Simultaneously, the HbA1c decreased to 5.5%, and antidiabetic therapy was discontinued. Six months after the last dose of atezolizumab, the patient visited the emergency room because of anorexia, dry mouth, and fatigue. Laboratory findings were as follows: blood glucose was 668 mg/dL, glycated hemoglobin (HbA1c) was 8.8%, urine ketone was 2+, sodium (Na) was 127 mmol/L, potassium (K) was 6.5 mmol/L, creatinine (Cre) was 1.43 mg/dL, and arterial pH was 7.29. Based on these findings, his presentation was consistent with fulminant type 1 diabetes mellitus (T1DM) complicated by diabetic ketoacidosis (DKA). Regular continuous insulin and saline administration was initiated in the intensive care unit, and acidosis and electrolyte abnormalities were corrected. His C-peptide was <0.03 ng/mL. His insulin secretory capacity was considered to be depleted, and he required continuous subcutaneous insulin injections. Glutamic acid decarboxylase and insulin autoantibodies were absent. The complete response persisted without further therapy until two years since the event.
RESUMEN
BACKGROUND: Surgical treatments such as lymphaticovenular anastomosis (LVA) are widely used in addition to conservative treatment of secondary lymphedema. However, their indications and effectiveness for primary lymphedema are unclear. This study aims to objectively demonstrate the effectiveness of LVA for adult-onset primary lymphedema from various perspectives. METHODS: We retrospectively examined patients with primary lower limb lymphedema who underwent LVA between January 2018 and December 2021 and were 21 or older. Treatment effects were evaluated using lymphoscintigraphy, questionnaires, body mass index, extracellular fluid ratio, and lymphedema index preoperatively and 6 months postoperatively. The LVA was performed under general anesthesia. RESULTS: We evaluated 11 patients (11 lower limbs). Out of seven patients with complete obstruction preoperatively, all presented partial obstruction according to the Taiwan Lymphoscintigraphy Staging classification with a significant decrease in the score. Significant improvements were observed in clinical symptoms ("hardness") and in quality of life ("appearance" and "ease of wearing compression garments") assessments. A significant change was observed in the extracellular water ratio but not in lower extremity lymphedema index (LELindex). CONCLUSION: LVA was suggested as one of the potential treatment options for patients with adult-onset primary lymphedema in whom lymphatic flow was confirmed by lymphoscintigraphy. In addition to clinical symptoms and physical examination, the evaluation of adult-onset primary lymphedema should include the patient's quality of life.
Asunto(s)
Vasos Linfáticos , Linfedema , Adulto , Humanos , Estudios Retrospectivos , Calidad de Vida , Extremidad Inferior/cirugía , Anastomosis Quirúrgica , Linfedema/diagnóstico por imagen , Linfedema/cirugía , Vasos Linfáticos/diagnóstico por imagen , Vasos Linfáticos/cirugía , Resultado del TratamientoRESUMEN
AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; Pï¼.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; Pï¼.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.
Asunto(s)
Anticoagulantes , COVID-19 , Hemorragia , Heparina , Humanos , Masculino , Femenino , Japón/epidemiología , Estudios Retrospectivos , Hemorragia/epidemiología , Hemorragia/inducido químicamente , COVID-19/epidemiología , COVID-19/complicaciones , COVID-19/mortalidad , Heparina/efectos adversos , Anciano , Persona de Mediana Edad , Incidencia , Anticoagulantes/efectos adversos , Factores de Riesgo , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Anciano de 80 o más Años , Tromboembolia/epidemiología , Tromboembolia/etiologíaRESUMEN
Non-traumatic chronic skin lesions are the second most common cause of tetanus. Herein, we describe an 85-year-old woman who presented with a chronically infected skin lesion. She developed tetanus while in hospital and died of respiratory failure, after refusing mechanical ventilation. Routine immunization against tetanus began in Japan during 1968; hence many people born before 1968 are unvaccinated. Mortality due to tetanus is high and the proportion with protective antibodies is low in older adults. Therefore, we recommend tetanus vaccination for older persons in Japan who have chronic skin lesions and have never been vaccinated.
Asunto(s)
Tétanos , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Tétanos/prevención & control , Gangrena , Vacunación , Toxoide Tetánico , AutopsiaRESUMEN
BACKGROUND: Lymphedema is an intractable disease that can be caused by injury to lymphatic vessels, such as by surgical treatments for cancer. It can lead to impaired joint mobility in the extremities and reduced quality of life. Chronic inflammation due to infiltration of various immune cells in an area of lymphedema is thought to lead to local fibrosis, but the molecular pathogenesis of lymphedema remains unclear. Development of effective therapies requires elucidation of the immunological mechanisms involved in the progression of lymphedema. The complement system is part of the innate immune system which has a central role in the elimination of invading microbes and acts as a scavenger of altered host cells, such as apoptotic and necrotic cells and cellular debris. Complement-targeted therapies have recently been clinically applied to various diseases caused by complement overactivation. In this context, we aimed to determine whether complement activation is involved in the development of lymphedema. RESULTS: Our mouse tail lymphedema models showed increased expression of C3, and that the classical or lectin pathway was locally activated. Complement activation was suggested to be involved in the progression of lymphedema. In comparison of the C3 knockout (KO) mouse lymphedema model and wild-type mice, there was no difference in the degree of edema at three weeks postoperatively, but the C3 KO mice had a significant increase of TUNEL+ necrotic cells and CD4+ T cells. Infiltration of macrophages and granulocytes was not significantly elevated in C3 KO or C5 KO mice compared with in wild-type mice. Impaired opsonization and decreased migration of macrophages and granulocytes due to C3 deficiency should therefore induce the accumulation of dead cells and may lead to increased infiltration of CD4+ T cells. CONCLUSIONS: Vigilance for exacerbation of lymphedema is necessary when surgical treatments have the potential to injure lymphatic vessels in patients undergoing complement-targeted therapies or with complement deficiency. Future studies should aim to elucidate the molecular mechanism of CD4+ T cell infiltration by accumulated dead cells.
Asunto(s)
Vasos Linfáticos , Linfedema , Humanos , Animales , Ratones , Calidad de Vida , Linfedema/etiología , Linfedema/metabolismo , Linfedema/patología , Linfocitos T CD4-Positivos , Inflamación , Ratones Noqueados , Ratones Endogámicos C57BLRESUMEN
Background: We aimed to investigate chronological changes in the characteristics of participants in a coronavirus disease 2019 convalescent plasma donation study that may benefit optimal collection methods in the future. Methods: Data from a convalescent plasma donation study from April 30, 2020 to November 5, 2021 were collected and analyzed. After August 23, 2021, an interim analysis of factors linked to higher antibody titers led us to restrict our participant recruitment criteria to participants who were within 4 months of disease onset and to patients who were otherwise most likely to have sufficiently high antibody titers. Overall, 1299 samples from 1179 patients were analyzed. Results: Over the duration of the study, 35.9% of the samples were deemed eligible for convalescent plasma collection. The overall eligibility rate initially declined, dipping to <20% after one year. During this period, the proportion of enrolled samples from patients who had severe illness also declined, and the proportion of samples from participants who were >120 days post disease onset increased. After the addition of days from onset and vaccination status to our participant recruitment criteria, the eligibility rate improved significantly. Conclusions: As outbreaks of emerging infectious disease occur, it is desirable to construct and implement a scheme for convalescent plasma donation promptly and to monitor the eligibility rate over time. If it declines, promptly analyze and resolve the associated factors. Additionally, vaccine development and infection prevalence are likely to influence the effective recruitment of participants with high antibody titers.
RESUMEN
Background: The corpus cavernosum (CC) containing sinusoids plays fundamental roles for erection. Analysis of pathological changes in the erectile system is studied by recent experimental systems. Various in vitro models utilizing genital mesenchymal-derived cells and explant culture systems are summarized. Methods: 3D reconstruction of section images of murine CC was created. Ectopic chondrogenesis in aged mouse CC was shown by a gene expression study revealing the prominent expression of Sox9. Various experimental strategies utilizing mesenchyme-derived primary cells and tissue explants are introduced. Main Findings: Possible roles of Sox9 in chondrogenesis and its regulation by several signals are suggested. The unique character of genital mesenchyme is shown by various analyses of external genitalia (ExG) derived cells and explant cultures. Such strategies are also applied to the analysis of erectile contraction/relaxation responses to many signals and aging process. Conclusion: Erectile dysfunction (ED) is one of the essential topics for the modern aged society. More comprehensive studies are necessary to reveal the nature of the erectile system by combining multiple cell culture strategies.
RESUMEN
BACKGROUND: This study aimed to assess the relationship between immune response adverse events (irAEs) and treatment efficacy in patients with extensive disease small cell lung cancer (ED-SCLC). METHODS: We retrospectively evaluated the clinical effects in 40 ED-SCLC patients who had received immune-checkpoint inhibitors (ICIs), platinum agents, and etoposide between September 2019 and September 2021. We identified and compared patients belonging to two groups: irAE and non-irAE. RESULTS: Fifteen patients experienced irAEs, and 25 did not. The median progression-free survival in patients with irAE was longer than that in patients without irAE (12.6 months [95% CI: 6.3-19.3 months] vs. 7.2 months [95% CI: 5.8-7.9 months], p = 0.0108). However, the median overall survival (OS) was similar between irAE and non-irAE groups (27.6 months [95% CI: 15.4-NA] vs. 24.9 months [95% CI: 13.7-NA], p = 0.268). Seven (46.7%) in the irAE group and 20 (80%) in the non-irAE group received sequential therapy. The median OS was prolonged in patients who received first- and second-line therapy than in those who received first-line therapy alone (27.6 months [95% CI: 19.2-NA] vs. 6.6 months [95% CI: 0.3-NA], p = 0.053). Grade ⧠3 irAEs occurred in five (12.5%) patients. Among them, grade 5 irAEs were observed in two patients, including exacerbation of polymyositis and pulmonary arterial embolism. CONCLUSION: In this study, the development of irAEs did not affect OS in patients with ED-SCLC who received platinum-based agents, etoposide, or ICI therapy. We determined that managing irAEs and administering first- and second-line therapies could contribute to prolonged OS.
Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Nivolumab/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Antineoplásicos Inmunológicos/uso terapéutico , Estudios Retrospectivos , Etopósido/efectos adversos , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: The characteristics and clinical consequences of bacteremia in older people, who are highly susceptible to infections, need to be clarified. This study aimed to determine the epidemiological characteristics, prognosis, and predictors of 7-day mortality in patients with community-acquired (CA), healthcare-associated (HCA), and hospital-onset (HO) bacteremia in older adults aged ≥65 years. METHODS: Patients aged ≥65 years with positive blood cultures between April 1, 2015, and March 31, 2018, were divided into three groups: pre-old (65-74 years), old (75-89 years), and super-old (≥90 years). Characteristics based on medical exposure, including CA, HCA, and HO, were also compared and factors related to mortality were identified. RESULTS: Overall, 1716 episodes of bacteremia were identified in 1415 patients. Of the 1211 episodes without contamination, 32.8%, 54.3%, and 12.9% occurred in pre-old, old, and super-old patients. Central line-associated bloodstream infections were more common in pre-old patients and urinary tract infections in the old and super-old. The 7-day mortality rates in the pre-old, old, and super-old groups were 7.4%, 5.8%, and 14.2% (P = 0.002), respectively. Multivariable logistic regression showed that super-old age (adjusted odds ratio, aOR: 2.09 [1.13-3.88], P = 0.019) and HO bacteremia (aOR: 1.97 [1.18-3.28], P = 0.010) were independent risk factors for 7-day mortality. Infectious disease consultation had a protective effect on 7-day mortality (aOR: 0.59 [0.35-0.99], P = 0.047). CONCLUSIONS: The epidemiology of bacteremia differs among older people; thus, they should not be treated as a single entity. A careful approach is needed for the optimal management of bacteremia in these vulnerable patients.
Asunto(s)
Bacteriemia , Infecciones Comunitarias Adquiridas , Infección Hospitalaria , Anciano , Humanos , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Bacteriemia/etiología , Bacteriemia/mortalidad , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/mortalidad , Pueblos del Este de Asia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/mortalidad , Anciano de 80 o más Años , Japón/epidemiologíaRESUMEN
The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract.
Asunto(s)
Líquidos Corporales , Estrechez Uretral , Animales , Ratones , Uretra , Proliferación Celular , Cicatrización de HeridasRESUMEN
BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. METHODS: This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. RESULTS: Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5-80.5] years; Charlson Comorbidity Index 2 [0-4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500-2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32-61; 21-86), 29 (19-82; 8-251), and 86 (59-125; 37-337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5-350) days. CONCLUSIONS: In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.
Asunto(s)
Bacteriemia , Osteomielitis , Adulto , Femenino , Humanos , Anciano , Masculino , Antibacterianos/uso terapéutico , Cefalexina/uso terapéutico , Meticilina/farmacología , Staphylococcus aureus , Absceso , Estudios Retrospectivos , Bacteriemia/tratamiento farmacológico , Osteomielitis/tratamiento farmacológicoRESUMEN
Teleost fishes exhibit complex sexual characteristics in response to androgens, such as fin enlargement and courtship display. However, the molecular mechanisms underlying their evolutionary acquisition remain largely unknown. To address this question, we analyse medaka (Oryzias latipes) mutants deficient in teleost-specific androgen receptor ohnologs (ara and arb). We discovered that neither ar ohnolog was required for spermatogenesis, whilst they appear to be functionally redundant for the courtship display in males. However, both were required for reproductive success: ara for tooth enlargement and the reproductive behaviour eliciting female receptivity, arb for male-specific fin morphogenesis and sexual motivation. We further showed that differences between the two ar ohnologs in their transcription, cellular localisation of their encoded proteins, and their downstream genetic programmes could be responsible for the phenotypic diversity between the ara and arb mutants. These findings suggest that the ar ohnologs have diverged in two ways: first, through the loss of their roles in spermatogenesis and second, through gene duplication followed by functional differentiation that has likely resolved the pleiotropic roles derived from their ancestral gene. Thus, our results provide insights into how genome duplication impacts the massive diversification of sexual characteristics in the teleost lineage.
Asunto(s)
Oryzias , Receptores Androgénicos , Animales , Masculino , Femenino , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Peces/genética , Peces/metabolismo , Evolución Biológica , Evolución Molecular , Oryzias/genética , Oryzias/metabolismoRESUMEN
Embryonic external genitalia (genital tubercle [GT]) protrude from the cloaca and outgrow as cloacal development progresses. Individual gene functions and knockout phenotypes in GT development have been extensively analyzed; however, the interactions between these genes are not fully understood. In this study, we investigated the role of p63, focusing on its interaction with the Shh-Wnt/Ctnnb1-Fgf8 pathway, a signaling network that is known to play a role in GT outgrowth. p63 was expressed in the epithelial tissues of the GT at E11.5, and the distal tip of the GT predominantly expressed the ΔNp63α isoform. The GTs in p63 knockout embryos had normal Shh expression, but CTNNB1 protein and Fgf8 gene expression in the distal urethral epithelium was decreased or lost. Constitutive expression of CTNNB1 in p63-null embryos restored Fgf8 expression, accompanied by small bud structure development; however, such bud structures could not be maintained by E13.5, at which point mutant GTs exhibited severe abnormalities showing a split shape with a hemorrhagic cloaca. Therefore, p63 is a key component of the signaling pathway that triggers Fgf8 expression in the distal urethral epithelium and contributes to GT outgrowth by ensuring the structural integrity of the cloacal epithelia. Altogether, we propose that p63 plays an essential role in the signaling network for the development of external genitalia.
Asunto(s)
Genitales , Vía de Señalización Wnt , Animales , Ratones , Regulación del Desarrollo de la Expresión Génica , Genitales/metabolismo , Proteínas Hedgehog/genéticaRESUMEN
AIMS/INTRODUCTION: Although several noninvasive predictive markers for fatty liver and metabolic markers have been used for fatty liver prediction, whether such markers can also predict metabolic-associated fatty liver disease (MAFLD) remains unclear. We aimed to examine the ability of existing fatty liver or metabolic markers to predict MAFLD. MATERIALS AND METHODS: Participants in a high-volume center in Tokyo were classified into groups with and without MAFLD, based on the presence of metabolic abnormalities and fatty liver diagnosed through abdominal ultrasonography, between 2008 and 2018. The diagnostic abilities of three fatty liver markers: fatty liver index (FLI), hepatic steatosis index (HSI), and lipid accumulation product (LAP), and three common metabolic markers: waist-to-height ratio (WHR), body mass index (BMI), and waist circumference (WC), for predicting MAFLD, were evaluated. Analyses stratified by MAFLD subtypes were performed. RESULTS: Of 92,374 individuals, 19,392 (36.1%) had MAFLD. The diagnostic performances for MAFLD prediction, measured as c-statistics, for FLI, HSI, LAP, WHR, BMI, and WC were 0.906, 0.892, 0.878, 0.844, 0.877, and 0.878, respectively. Optimal cutoff values for diagnosing MAFLD for FLI, HSI, LAP, WHR, BMI, and WC were 20.3, 32.7, 20.0, 0.49, 22.9, and 82.1, respectively. Analyses stratified by MAFLD subtypes, based on BMI and metabolic/glycemic abnormalities, suggested that FLI and HSI had acceptable (c-statistics >0.700) diagnostic abilities throughout all the analyses. CONCLUSIONS: All six markers were excellent predictors of MAFLD in diagnosing among the general population, with FLI and HSI particularly useful among all sub-populations.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Triglicéridos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Pruebas de Función Hepática , Abdomen , BiomarcadoresRESUMEN
Transient Receptor Potential (TRP) ion channels mediate the influx of cations into cells responding to chemical or physical stimuli. TRP vanilloid 1 (TRPV1) regulates cutaneous functions. Its function in cutaneous wound healing, however, has not been clarified. The current study elucidated the role of TRPV1 in cutaneous wound healing of dorsal circular excisional injury using Trpv1-null (KO) and wild type (WT) male/female C57BL/6 mice. Macroscopic observation showed that the remaining cutaneous lesion was significantly larger in KO than that of WT at postoperative days (POD) 7 and 10. Histological analysis showed significantly delayed re-epithelialization in KO at POD7. The number of macrophages in KO and WT similarly returned to the reduced state from POD4 to POD7. Whereas, the number of neutrophils in KO did not significantly return to the reduced state, in contrast to WT. Of note, The H3Cit-labeled NETs (Neutrophil Extracellular Traps) formation of KO was prominently increased both in POD4 and 7. The current results suggest that the loss of TRPV1 induces prolonged neutrophilic inflammation and NETs formation, retarding murine cutaneous wound healing in vivo. This study provides a possible link with TRPV1 and neutrophilic regulation in cutaneous wound healing.