Excess generation and activation of naturally arising memory-phenotype CD4+ T lymphocytes are inhibited by regulatory T cells in steady state.

Conventional CD4+ T lymphocytes consist of naïve, foreign antigen-specific memory, and self-antigen-driven memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells tonically proliferate in response to self-antigens and differentiate into the T-bet+ subset in steady state. How excess proliferation and differentiation of MP cells are inhibited remains unclear. Given immunosuppressive function of regulatory T cells (Tregs), it is possible that they are also involved in inhibition of spontaneous MP cell activation. Here we show using Foxp3-diphtheria toxin receptor-transgenic mice that both MP and naïve CD4+ T cells spontaneously proliferate and differentiate into Th1 cells upon acute Treg depletion. At an early time point post Treg depletion, MP as compared to naïve CD4+ T cells are preferentially activated while at a later stage, the response is dominated by activated cells originated from the naïve pool. Moreover, we argue that MP cell proliferation is driven by TCR and CD28 signaling whereas Th1 differentiation mediated by IL-2. Furthermore, our data indicate that such activation of MP and naïve CD4+ T lymphocytes contribute to development of multi-organ inflammation at early and later time points, respectively, after Treg ablation. Together our findings reveal that Tregs tonically inhibit early, spontaneous proliferation and Th1 differentiation of MP CD4+ T lymphocytes as well as late activation of naïve cells, thereby contributing to maintenance of T cell homeostasis.

Association of Omega-3 Polyunsaturated Fatty Acids with Sarcopenia in Liver Cirrhosis Patients with Hepatocellular Carcinoma.

Background and Aims: Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC. Methods: In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography. Results: Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006). Conclusions: A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

Changes in Mutations of Cell-Free DNA and Liver Tumor Tissue in Patients with Advanced Hepatocellular Carcinoma before and after Introduction of Lenvatinib.

INTRODUCTION: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy. METHODS: We analyzed cfDNA before and 6-8 weeks after the start of treatment in 20 advanced HCC patients who started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, -124C>T and -146C>T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. Computerized tomography evaluation was performed at 6-8 weeks and 3-4 months to assess the efficacy. RESULTS: Frequencies of TERT promoter, CTNNB1, and TP53 mutations in pretreatment cfDNA were 45%, 65%, and 65%, but 53%, 41%, and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression. CONCLUSION: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs.

Type 2 Diabetes Mellitus is a Risk Factor for Skeletal Muscle Loss in the Course of Dietary Treatment for Patients with Metabolic Dysfunction-associated Steatotic Liver Disease.

Objective This study assessed the impact of dietary therapy and reduced body weight on the loss of skeletal muscle in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods This was a single-center retrospective observational study. We enrolled 129 patients with MASLD who had undergone dietary therapy at our facility. We assessed skeletal muscle mass using a bioelectrical impedance analysis (BIA) at the start of dietary treatment and 12 months after the first assessment. Variables related to muscle reduction were analyzed using a logistic regression model. Results One hundred and eighteen cases were analyzed, excluding those with missing data. In the muscle reduction group, there were more subjects with body weight reduction than in the control group (68% and 40%, respectively, p =0.002), and their body mass index (BMI) was decreased (-0.7 kg/m2 and +0.3 kg/m2, respectively, p =0.0003). There was a significant correlation between the changes in the BMI and muscle mass (R =0.48, p <0.0001). We standardized muscle mass change by dividing it by weight change to analyze the severe decrease in muscle mass compared to weight change. A logistic regression analysis revealed that type 2 diabetes mellitus (T2DM) was an independent variable related to severe skeletal muscle loss (odds ratio, 2.69; 95% CI: 1.13-6.42, p =0.03). Conclusion Weight loss is associated with skeletal muscle loss during dietary treatment for MASLD. T2DM is a risk factor for severe skeletal muscle loss.

Three consecutive cases of acute liver failure in young women due to acetaminophen overdose: insights into Japanese social issues and transplantation landscape.

Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19 years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.

Pioneering cord blood transplantation in relapsed/refractory HIV-related lymphoma: a case study with concurrent intramuscular antiretroviral therapy.

A 44-year-old HIV-positive man diagnosed with diffuse large B-cell lymphoma in 2021 achieved complete remission with six cycles of R-CHOP therapy but had a relapse in November 2022. ESHAP therapy failed to induce remission, leading to complete remission with four cycles of Pola-BR therapy. Post-failure of autologous stem cell harvest, cord blood transplantation (CBT) was performed in June 2023. Notably, this case used recently approved intramuscular antiretroviral therapy (ART) with cabotegravir and rilpivirine, addressing gastrointestinal complications during CBT. This innovative use of intramuscular ART in the treatment of malignancy represents a first in the field, offering a pioneering approach to HIV-related lymphoma.

A predictive model for HIV-related lymphoma.

OBJECTIVES: To address the paucity of HIV-related lymphoma (HRL)-specific prognostic scores for the Japanese population by analyzing domestic cases of HRL and constructing a predictive model. DESIGN: A single-center retrospective study coupled with a review of case reports of HRL. METHODS: We reviewed all patients with HRL treated at our hospital between 2007 and 2023 and conducted a comprehensive search for case reports of HRL from Japan using public databases. A multivariate analysis for overall survival (OS) was performed using clinical parameters, leading to the formulation of the HIV-Japanese Prognostic Index (HIV-JPI). RESULTS: A total of 19 patients with HRL were identified in our institution, whereas the literature review yielded 44 cases. In the HIV-JPI, a weighted score of 1 was assigned to the following factors: age at least 45 years, HIV-RNA at least 8.0×10 4  copies/ml, Epstein-Barr virus-encoded small RNA positivity, and Ann Arbor classification stage IV. The overall score ranged from 0 to 4. We defined the low-risk group as scores ranging from 0 to 2 and the high-risk group as scores ranging from 3 to 4. The 3-year OS probability of the high-risk group [30.8%; 95% confidence interval (CI): 9.5-55.4%) was significantly poorer than that of the low-risk group (76.8%; 95% CI: 52.8-89.7%; P  < 0.01). CONCLUSION: This retrospective analysis established pivotal prognostic factors for HRL in Japanese patients. The HIV-JPI, derived exclusively from Japanese patients, highlights the potential for stratified treatments and emphasizes the need for broader studies to further refine this clinical prediction model.

An indocyanine green fluorescence-guided operation for diagnosing and treating pleuroperitoneal communication.

Pleuroperitoneal communication occurs when ascites moves from the abdominal cavity to the pleural cavity via a diaphragmatic fistula. Managing large pleural fluid volumes is challenging, often requiring an operation. Identifying small diaphragmatic fistulas during the operation can be problematic, but ensuring their detection improves outcomes. This video tutorial presents a recent empirical case in which we successfully identified and closed a pleuroperitoneal contact using a thoracoscopic surgical procedure aided by indocyanine green fluorescence imaging. The patient, a 66-year-old woman, was hospitalized due to acute dyspnoea from a right thoracic pleural effusion during hepatic ascites treatment for cirrhosis. Because ascites decreased with pleural fluid drainage, surgical intervention was considered due to suspicion of a pleuroperitoneal connection. During the operation, indocyanine green was injected intraperitoneally, and near-infrared fluorescence-guided thoracoscopy pinpointed the location of the diaphragmatic fistula. The fistula was sutured and reinforced with a polyglycolic acid sheet and fibrin glue. Detecting the fistula intraoperatively is crucial to prevent recurrence, and the indocyanine green fluorescence method is a safe and effective technique for detecting small fistulas.

Projection Mapping under Environmental Lighting by Replacing Room Lights with Heterogeneous Projectors.

Projection mapping (PM) is a technique that enhances the appearance of real-world surfaces using projected images, enabling multiple people to view augmentations simultaneously, thereby facilitating communication and collaboration. However, PM typically requires a dark environment to achieve high-quality projections, limiting its practicality. In this paper, we overcome this limitation by replacing conventional room lighting with heterogeneous projectors. These projectors replicate environmental lighting by selectively illuminating the scene, excluding the projection target. Our contributions include a distributed projector optimization framework designed to effectively replicate environmental lighting and the incorporation of a large-aperture projector, in addition to standard projectors, to reduce high-luminance emitted rays and hard shadows-undesirable factors for collaborative tasks in PM. We conducted a series of quantitative and qualitative experiments, including user studies, to validate our approach. Our findings demonstrate t hat our projector-based lighting system significantly enhancesthe contrast and realism of PM results even under e nvironmental lighting compared to typical lights. Furthermore, our method facilitates a substantial shift in the perceived color mode from the undesirable aperture-color mode, where observers perceive the projected object as self-luminous, to the surface-color mode in PM.

A materials informatics driven fine-tuning of triazine-based electron-transport layer for organic light-emitting devices.

Materials informatics in the development of organic light-emitting diode (OLED) related materials have been performed and exhibited the effectiveness for finding promising compounds with a desired property. However, the molecular structure optimization of the promising compounds through the conventional approach, namely the fine-tuning of molecules, still involves a significant amount of trial and error. This is because it is challenging to endow a single molecule with all the properties required for practical applications. The present work focused on fine-tuning triazine-based electron-transport materials using machine learning (ML) techniques. The prediction models based on localized datasets containing only triazine derivatives showed high prediction accuracy. The descriptors from density functional theory calculations enhanced the prediction of the glass transition temperature. The proposed multistep virtual screening approach extracted the promising triazine derivatives with the coexistence of higher electron mobility and glass transition temperature. Nine selected triazine compounds from 3,670,000 of the initial search space were synthesized and used as the electron transport layer for practical OLED devices. Their observed properties matched the predicted properties, and they enhanced the current efficiency and lifetime of the device. This paper provides a successful model for the ML assisted fine-tuning that effectively accelerates the development of practical materials.

Correlation between preoperative CT scan of the paraspinal, psoas, and gluteus muscles and postoperative ambulatory status in patients with femoral neck fractures.

BACKGROUND: This study aimed to investigate the relationship between femoral neck fractures and sarcopenia. METHODS: This was a retrospective analysis of 92 patients with femoral neck fractures, from September 2017 to March 2020, who were classified into high ambulatory status (HG) and low ambulatory status (LG) groups. Ambulatory status was assessed before surgery, one week after surgery, at discharge, and during the final follow-up. To evaluate sarcopenia, muscle mass and fatty degeneration of the muscles were measured using preoperative CT. An axial slice of the superior end of the L5 vertebra was used to evaluate the paraspinal and psoas muscles, a slice of the superior end of the femoral head for the gluteus maximus muscle, and a slice of the inferior end of the sacroiliac joint for the gluteus medius muscle. The degeneration of the muscles was evaluated according to the Goutallier classification. RESULTS: The cross-sectional area of the gluteus medius and paraspinal muscles was significantly correlated with ambulatory status before the injury, at discharge, and during the final follow-up. CONCLUSIONS: Measurement of the gluteus medius and paraspinal muscles has the potential to evaluate sarcopenia and predict ambulatory status after femoral neck fractures.

Efficient Distortion-Free Neural Projector Deblurring in Dynamic Projection Mapping.

Dynamic Projection Mapping (DPM) necessitates geometric compensation of the projection image based on the position and orientation of moving objects. Additionally, the projector's shallow depth of field results in pronounced defocus blur even with minimal object movement. Achieving delay-free DPM with high image quality requires real-time implementation of geometric compensation and projector deblurring. To meet this demand, we propose a framework comprising two neural components: one for geometric compensation and another for projector deblurring. The former component warps the image by detecting the optical flow of each pixel in both the projection and captured images. The latter component performs real-time sharpening as needed. Ideally, our network's parameters should be trained on data acquired in an actual environment. However, training the network from scratch while executing DPM, which demands real-time image generation, is impractical. Therefore, the network must undergo pre-training. Unfortunately, there are no publicly available large real datasets for DPM due to the diverse image quality degradation patterns. To address this challenge, we propose a realistic synthetic data generation method that numerically models geometric distortion and defocus blur in real-world DPM. Through exhaustive experiments, we have confirmed that the model trained on the proposed dataset achieves projector deblurring in the presence of geometric distortions with a quality comparable to state-of-the-art methods.

Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients.

AIM: Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitis B virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development. METHODS: Among a total of 882 chronically hepatitis B virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1 year of treatment was obtained were evaluated for the incidence of HCC. RESULTS: The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1 year (P < 0.001), but the reduction was small at 2 years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5 years, the area under the curve of FIB-4 at 1 year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10 years, P < 0.001). Additionally, an abnormal alanine aminotransferase (≥31 U/L) at 1 year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1) score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10 years, P < 0.001). CONCLUSIONS: FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1 year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

Out-of-hospital cardiac arrest patients during the coronavirus disease 2019 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic had severe impact on the outcome of out-of-hospital cardiac arrest (OHCA) patients and the possibility of bystander cardiopulmonary resuscitation (CPR). Previous studies focused only on the short periods of the pandemic and reported a significant increase in the number of infections. In a retrospective cohort study we aimed to compare the outcomes of OHCA patients 1 year before and 1 year after the onset of COVID-19. Data of 519 OHCA patients during the pre-pandemic (January-December 2019; 262 patients) and intra-pandemic (April 2020-March 2021; 257 patients) periods in Yokohama Municipal Hospital, Japan were collected and analysed retrospectively. The study outcomes were the return of spontaneous circulation (ROSC), admission to hospital, survival to discharge, and cerebral performance category at discharge. The intra-pandemic period was associated with decreased bystander CPR (P = 0.004), prolonged transport time (P < 0.001), delayed first adrenaline administration (P < 0.001), and decrease in ROSC (P = 0.023). Logistic regression analysis revealed that the following factors were significantly associated with ROSC: "pandemic", "shockable initial waveform", and "witness presence".

Comparing Bone Fusion Rates Between Novel Unidirectional Porous Tricalcium Beta-Phosphate and Autologous Bone in Lumbar Lateral Interbody Fusion: A Two-Year Radiographic Outcome Study.

This retrospective cohort study aims to examine the potential differences in bone fusion between autologous bone and artificial bone in the lumbar lateral interbody fusion at 2two years post-surgery. The bone fusions performed in 15 cases and at 34 intervertebral levels were compared to assess the differences between the artificial bone, Affinos® (Kuraray Co., Tokyo, Japan), and autogenous bone. Two years post-surgery, we evaluated computed tomography (CT) multi-planar reconstruction images in the coronal and sagittal planes. One year after surgery, out of the 24 windows, 17 (70.8%) windows transplanted with autologous bones showed bone fusion. Additionally, out of the 38 windows, 18 (47.4%) windows transplanted with Affinos® showed bone fusion. Two years post-surgery, out of the 24 windows, 19 (79.2%) windows transplanted with autologous bones showed bone fusion. Additionally, out of the 38 windows, 30 (79.0%) windows transplanted with Affinos® showed bone fusion, and no difference was observed in the fusion rate at two years post-surgery (P = 0.238). In cases using Affinos® for transplanted bone, the bone fusion rate increased between one and two years. The rate of bony fusion using Affinos® in lateral lumbar interbody fusion (LLIF) cages is at par with that of autologous bone grafts at two years post-surgery. Affinos® is a promising candidate for graft material in LLIF surgery.

A new model to estimate duration of survival in patients with hepatocellular carcinoma with BCLC intermediate stage.

It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in patients who receive multiple treatments in HCC. We aimed to establish a new model of survival prediction in patients with intermediate stage HCC to establish standards in the recent and coming multi-MTA era. This analysis was prepared using a data set of 753 patients diagnosed HCC prior to 2017. Multiple regression analysis showed age, naïve or recurrence, the size of the largest tumor nodule, the number of nodules, total bilirubin, albumin and α-fetoprotein as independent predictors of survival. A Weibull model had the best fit and, based on these predictors, we established a new predicted survival model. The survival duration can be predicted the proposed model; EXP (4.02580 + (- 0.0086253) × age + (- 0.34667) × (naïve/recurrence) + (- 0.034962) × (number of nodules) + (- 0.079447) × (the size of the largest nodule) + (- 0.21696) × (total bilirubin) + 0.27912 × (albumin) + (- 0.00014741) × (α-fetoprotein)) × (- natural logarithm(0.5))^0.67250. This model is useful for the planning and evaluating the efficacy of recent sequential therapies in multi-MTA era.

Effect of platelet-rich plasma on the acceleration of graft bone catabolism in lateral lumbar interbody fusion in a short-term assessment.

This study aimed to demonstrate whether impregnating the graft bone with platelet-rich plasma (PRP) accelerates graft bone catabolism in lateral lumbar interbody fusion (LLIF). Consecutive patients who underwent LLIF were assessed. Of the two spaces for bone grafts in the intervertebral cage, one space was filled with graft bone impregnated with PRP, and the other was filled with graft bone without PRP, which divided the graft bones into PRP and non-PRP groups. The mean Hounsfield units (HU) of the graft bone at the center of the cage space in the coronal and axial slices were measured using computed tomography (CT) images 1 week and 6 months after surgery. The delta value of HU from 1 week to 6 months after surgery was calculated for the PRP and non-PRP groups. We compared the delta values of the HU between the two groups. The PRP and non-PRP groups comprised 16 bone grafts. In the coronal slices, the HU value in the PRP group (delta value: 526.1 ± 352.2) tended to have a greater decrease at 6 months after surgery compared with that in the non-PRP group (delta value: 217.6 ± 240.4) (p = 0.065). In the axial slices, the HU value in the PRP group (delta value: 501.3 ± 319.6) was significantly decreased at 6 months after surgery compared with that in the non-PRP group (delta value: 159.2 ± 215.3) (p = 0.028). Impregnating the graft-bone with PRP accelerated graft bone catabolism in LLIF within 6 months after surgery.

[Achieving diversity in the medical field:a survey of female physicians and medical staff in the Department of Gastroenterology].

From the perspective of diversity in the medical field, the relationship between physicians and medical staff is one of the important factors. In this study, a survey was conducted on female doctors for 136 medical staff who are deeply involved in gastroenterology. Furthermore, another survey was conducted on 10 female doctors in gastroenterology regarding their relationship with the medical staff and their work-life balance. Consequently, 89% of the medical staff had experienced a situation where they relied on female doctors. Seventy-eight percent felt a necessity for female doctors, and it was observed that the demand for female doctors in gastroenterology would remain high in the future. Conversely, regarding the necessity of female doctors, 22% responded "neither agree nor disagree," and several of them believed that the personal qualities of a doctor were the most significant versus being a female. Moreover, it was noted that the idea of genderless thinking is becoming prevalent in the medical field. In addition, half of the female doctors considered gastroenterology to be a workplace that is easy for female doctors. The most common reason was that it broadens the options for working styles because skills, including gastrointestinal endoscopy and ultrasonography, can be acquired. Ninety percent of female doctors had no experience of trouble with medical staff due to being female. Conversely, 80% responded that they could work smoothly with staff in their interactions with female patients. Since medical treatment is based on gender differences, it is difficult not to be aware of them. Creating an environment wherein female doctors are freed from gender stereotypes and can utilize being female as one of their abilities while responding to the needs of patients and the medical field will be necessary.

Effectiveness of tacrolimus in a case of immune checkpoint inhibitor-induced hepatotoxicity that was refractory to steroids and mycophenolate mofetil.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-mediated hepatotoxicity (IMH), and corticosteroids and mycophenolate mofetil (MMF) are recommended for the treatment of IMH. However, there is no consensus on the treatment of IMH refractory to these drugs. Here, we report a case of refractory IMH that was successfully treated with tacrolimus. A 69-year-old man presented with liver injury after receiving durvalumab, an ICI, for lung cancer. He was diagnosed with IMH and received corticosteroids including methylprednisolone pulses and MMF, but his liver damage did not improve. Liver histology showed infiltration of inflammatory cells, mainly CD8 + T cells, in the portal area. Tacrolimus was added to corticosteroid and MMF to suppress mainly T cells. After the tacrolimus administration, the liver damage promptly improved. Since IMH is thought to be caused by activated CD8 + T-cell infiltration, T-cell suppression may be an effective treatment. This case suggests that tacrolimus may be an effective option for IMH refractory to corticosteroids or MMF if CD8 + T-cell infiltration is confirmed in the liver tissue.

Analysis of evolutionary and functional features of the bullfrog SULT1 family.

We identified the bullfrog Rana catesbeiana sulfotransferase 1 (SULT1) family from the BLAST search tool of the public databases based on the SULT1 families of Nanorana parkeri, Xenopus laevis, and Xenopus tropicalis as queries, revealing the characteristics of the anuran SULT1 family. The results showed that the anuran SULT1 family comprises six subfamilies, four of which were related to the mammalian SULT1 subfamily. Additionally, the bullfrog has two SULT1Cc subfamily members that are consistent with the characteristics of the expanded Xenopus SULT1C subfamily. Several members of the bullfrog SULT1 family were suggested to play important roles in sulfation during metamorphosis. Among these, cDNAs encoding SULT1Cc1 and SULT1Y1 were cloned, and the sulfation activity was analyzed using recombinant proteins. The affinity for 2-naphthol and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the enzymatic reaction rate were higher in SULT1Cc1 than in SULT1Y1. Both the enzymes showed inhibitory effect of many thyroid hormones (THs) analogs on the sulfation of 2-naphthol. The potency of sulfation activities of SULT1Cc1 and SULT1Y1 against T4 indicated their possible role in the intracellular T4 clearance during metamorphosis.