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The growing use of plastic materials has resulted in a constant increase in the risk associated with microplastics (MPs). Ultra-violet (UV) light and wind break down modify MPs in the environment into smaller particles known as weathered MPs (WMPs) and these processes increase the risk of MP toxicity. The neurotoxicity of weathered polystyrene-MPs remains unclear. Therefore, it is important to understand the risks posed by WMPs. We evaluated the chemical changes of WMPs generated under laboratory-synchronized environmentally mimetic conditions and compared them with virgin MPs (VMPs). We found that WMP had a rough surface, slight yellow color, reduced molecular weight, and structural alteration compared with those of VMP. Next, 2 µg of â¼100 µm in size of WMP and VMP were orally administered once a day for one week to C57BL/6 male mice. Proteomic analysis revealed that the WMP group had significantly increased activation of immune and neurodegeneration-related pathways compared with that of the VMP group. Consistently, in in vitro experiments, the human brain-derived microglial cell line (HMC-3) also exhibited a more severe inflammatory response to WMP than to VMP. These results show that WMP is a more profound inflammatory factor than VMP. In summary, our findings demonstrate the toxicity of WMPs and provide theoretical insights into their potential risks to biological systems and even humans in the ecosystem.
Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Humanos , Camundongos , Masculino , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade , Poliestirenos/análise , Proteoma , Ecossistema , Proteômica , Camundongos Endogâmicos C57BL , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , EncéfaloRESUMO
Waste plastics are degraded into microplastics (MPs), which are easily accumulated in the human body through digestive tracts, via the food chain. Alcohol is a widely consumed chemical throughout the world with the ability to alter the intestinal barrier. For this reason, this study was aimed to investigate exact relevance between alcohol consumption and organ distributions of MPs in an ethanol feeding animal model characterized by disrupted intestinal mucosal barriers. In this study, C57BL/6 mice were separated into control, control + MP, ethanol (EtOH), and EtOH + MP groups. Mice in the EtOH group ingested a Lieber-DeCarli diet containing EtOH. Mice in the MP groups ingested 0.1 mg/kg fluorophore polymerized polystyrene microplastics via oral gavage polystyrene MPs via oral gavage. The EtOH + MP group showed higher MP accumulation in the liver than the control + MP group. The same pattern was observed in the intestines, spleen, and brain. This pattern was more prominent in the intestines, with the EtOH + MP group showing the most severe damage due to EtOH ingestion. This result suggests that the intestinal mucosa disruption caused by EtOH ingestion exacerbates MP accumulation in the organs. Moreover, hepatic steatosis was more severe in the EtOH + MP group than in the EtOH group, suggesting the secondary manifestation mediated by MP accumulation. This study reports a novel MP accumulation pattern in the body by providing novel insights into alcohol-induced gut permeability and microplastics toxicity from the perspective of gut-liver axis.
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Apocrine cystomatosis, also called epitrichial sweat gland cystomatosis, is a non-neoplastic condition characterised by multiple dilated cysts of sweat gland origin. Histopathologically, these cysts comprise two layers of cells: an inner layer of glandular epithelial cells and an outer layer of myoepithelial cells. A case of apocrine cystomatosis was admitted to a local hospital. The microscopic investigation revealed that some enlarged cysts showed the transition of glandular epithelial cells into a spindle, mesenchymal cell-like morphology. The epithelial-to-mesenchymal transition (EMT) has long been studied as a pathway for embryogenesis, organ development, and carcinogenesis. While various molecular factors, including cytokines and growth factors, are known to induce EMT, mechanical forces have also been proposed to initiate EMT. The present case describes a possible relationship between EMT occurring in a cystic condition and further pathological inspection.
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Although several studies have focused on cancer diagnosis and therapy, prostate cancer (PC) remains an intractable disease. Androgen deprivation therapy (ADT), which is used to treat early stage PC can lead to the development of castration-resistant prostate cancer (CRPC), which is highly associated with androgen receptor (AR) mutations. Nucleolar and coiled-body phosphoprotein 1 (NOLC1) is a chaperone that shuttles between the nucleus and the cytoplasm. Studies suggest that NOLC1 regulates PC progression; however, the underlying mechanisms remain unclear. Herein, we showed that NOLC1 knockdown suppresses PC cell proliferation by altering the signaling pathways and the expression of various proteins involved in DNA replication, amino acid metabolism, and RNA processing. Mechanistically, NOLC1 knockdown suppressed cell cycle progression by inhibiting AKT phosphorylation and ß-catenin accumulation. Finally, we showed that NOLC1 expression is higher in human PC than in human hyperplastic prostate tissues. Altogether, we demonstrated that NOLC1 knockdown suppresses the progression of both AR-positive and AR-negative PC cells by inducing changes in the expression of several genes leading to cell cycle arrest. Thus, NOLC1 might be a novel and promising therapeutic target for PC.
Assuntos
Neoplasias de Próstata Resistentes à Castração , beta Catenina , Masculino , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Fosforilação , Antagonistas de Androgênios , Linhagem Celular Tumoral , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismoRESUMO
Despite the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD), little is known about its underlying pathogenesis or specific treatment. The senescence marker protein 30 (SMP30), which regulates the biosynthesis of vitamin C (VC) in many mammals, except primates and humans, was recently recognized as a gluconolactonase. However, the precise relation between VC and lipid metabolism in NAFLD is not completely understood. Therefore, this study aimed to clearly reveal the role of VC in NAFLD progression. SMP30 knockout (KO) mice were used as a VC-deficient mouse model. To investigate the precise role of VC on lipid metabolism, 13- to 15-week-old SMP30 KO mice and wild-type mice fed a 60% high-fat diet were exposed to tap water or VC-containing water (1.5 g/L) ad libitum for 11 weeks. Primary mouse hepatocytes isolated from the SMP30 KO and wild-type mice were used to demonstrate the relation between VC and lipid metabolism in hepatocytes. Long-term VC deficiency significantly suppressed the progression of simple steatosis. The high-fat diet-fed VC-deficient SMP30 KO mice exhibited impaired sterol regulatory element-binding protein-1c activation because of excessive cholesterol accumulation in hepatocytes. Long-term VC deficiency inhibits de novo lipogenesis through impaired sterol regulatory element-binding protein-1c activation.
Assuntos
Deficiência de Ácido Ascórbico/metabolismo , Hepatócitos/metabolismo , Lipogênese/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Progressão da Doença , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos KnockoutRESUMO
Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.
Assuntos
Lanosterol , Triterpenos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Inonotus , Lanosterol/análogos & derivados , Lanosterol/farmacologia , CamundongosRESUMO
Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.
Assuntos
Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/análise , Doenças do Gato/patologia , Doenças do Cão/patologia , Peptídeos e Proteínas de Sinalização Intracelular/análise , Neoplasias Mamárias Animais/patologia , Animais , Biomarcadores Tumorais/análise , Mama/patologia , Neoplasias da Mama/diagnóstico , Doenças do Gato/diagnóstico , Gatos , Linhagem Celular Tumoral , Doenças do Cão/diagnóstico , Cães , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Animais/diagnóstico , PrognósticoRESUMO
Prostate cancer has the highest incidence among men in advanced countries, as well as a high mortality rate. Despite the efforts of numerous researchers to identify a gene-based therapeutic target as an effective treatment of prostate cancer, there is still a need for further research. The cathepsin gene family is known to have a close correlation with various cancer types and is highly expressed across these cancer types. This study aimed at investigating the correlation between the cathepsin A (CTSA) gene and prostate cancer. Our findings indicated a significantly elevated level of CTSA gene expression in the tissues of patients with prostate cancer when compared with normal prostate tissues. Furthermore, the knockdown of the CTSA gene in the representative prostate cancer cell lines PC3 and DU145 led to reduced proliferation and a marked reduction in anchorage-independent colony formation, which was shown to be caused by cell cycle arrest in the S phase. In addition, CTSA gene-knockdown prostate cancer cell lines showed a substantial decrease in migration and invasion, as well as a decrease in the marker genes that promote epithelial mesenchymal transition (EMT). Such phenotypic changes in prostate cancer cell lines through CTSA gene suppression were found to be mainly caused by reduced p38 MAPK protein phosphorylation; i.e. the inactivation of the p38 MAPK cell signaling pathway. Tumorigenesis was also found to be inhibited in CTSA gene-knockdown prostate cancer cell lines when a xenograft assay was carried out using Balb/c nude mice, and the p38 MAPK phosphorylation was inhibited in tumor tissues. Thus, the CTSA gene is presumed to play a key role in human prostate cancer tissues through high-level expression, and the suppression of the CTSA gene leads to the inhibition of prostate cancer cell proliferation, colony formation, and metastasis. The mechanism, by which these effects occur, was demonstrated to be the inactivation of the p38 MAPK signaling pathway.
Assuntos
Catepsina A/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias da Próstata/metabolismo , Transdução de Sinais/fisiologia , Animais , Sequência de Bases , Catepsina A/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , Metástase Neoplásica/genética , Metástase Neoplásica/fisiopatologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The cellular distribution of silica nanoparticles (NPs) in the liver is not well understood. Targeting specific cells is one of the most important issues in NP-based drug delivery to improve delivery efficacy. In this context, the present study analyzed the relative cellular distribution pattern of silica NPs in the liver, and the effect of surface energy modification on NPs. Hydrophobic NP surface modification enhanced NP delivery to the liver and liver sinusoid fFendothelial cells (LSECs). Conversely, hydrophilic NP surface modification was commensurate with targeting hepatic stellate cells (HSCs) rather than other cell types. There was no notable difference in NP delivery to Kupffer cells or hepatocytes, regardless of hydrophilic or hydrophobic NP surface modification, suggesting that both the targeting of hepatocytes and evasion of phagocytosis by Kupffer cells are not associated with surface energy modification of silica NPs. This study provides useful information to target specific cell types using silica NPs, as well as to understand the relationship between NP surface energy and the NP distribution pattern in the liver, thereby helping to establish strategies for cell targeting using various NPs.
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Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Fígado/metabolismo , Nanopartículas , Dióxido de Silício , Portadores de Fármacos/química , Células Endoteliais/metabolismo , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Células de Kupffer/metabolismo , Nanopartículas/química , Dióxido de Silício/química , Propriedades de Superfície , Distribuição TecidualRESUMO
Overhydration and sarcopenia, related to an individual's nutritional status, have been associated with increased cardiovascular mortality and poor prognosis in patients on hemodialysis. The purpose of this study was to investigate the prediction of overhydration and sarcopenia on mortality in patients on hemodialysis using a body composition monitor. We conducted a systematic review and meta-analysis using a random-effects model. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE and PubMed databases for all studies published prior to December 9, 2016 and reviewed the reference lists of relevant reviews, registered trials and relevant conference proceedings. The overhydration group (fluid excess, >15% vs. the normohydration group) and the low lean tissue index group ( <10%) were compared with a reference group. Six trials, consisting of 29,469 patients, were included in the pooled analysis. The pooled hazard ratio for overall survival of the overhydration group, compared with the reference normohydration group was 1.798 (95% confidence interval [CI]: 1.53-2.804, p = .001). The hazard ratio for mortality in the low lean tissue index group was 1.533 (95% CI, 1.411-1.644; p = .001) in the random-effects model. The results from the most recent study showed the greatest heterogeneity in the sensitivity analysis. Low lean tissue index and overhydration, measured using a body composition monitor, were associated with a high mortality rate in patients on hemodialysis.
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Composição Corporal , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Sarcopenia/mortalidade , Desequilíbrio Hidroeletrolítico/mortalidade , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Monitorização Fisiológica/métodos , Prognóstico , Modelos de Riscos Proporcionais , Sarcopenia/etiologia , Taxa de Sobrevida , Desequilíbrio Hidroeletrolítico/etiologiaRESUMO
A 5 yr old, 184 kg, and 262 cm total length female bottlenose dolphin Tursiops truncatus was found dead in a display after bloody discharge from the blowhole was observed 3 h prior to death. Pathological examination revealed fibrinous bronchopneumonia with prominent areas of necrosis (sequestra) and numerous Gram-negative bacilli within alveoli and in blood vessels of the lungs and liver and between muscle fibers. The cause of death was attributed to septicemia. Often, cases of fibrinous bronchopneumonia are characterized by bacteremia in the latter stages of infection, resulting in the death of the animal. Septicemia likely accounts for the ecchymoses and petechiae noted on the spleen, pancreas, forestomach, lungs, visceral peritoneum, and small intestine. Additional lesions included hemothorax, stable red frothy fluid in the trachea, and lymphoid depletion in the spleen and lymph nodes. Pure growth of Morganella morganii was isolated from the lungs, blood, liver, and blowhole mucosa. Sequencing of 16s rRNA of the isolated bacteria showed more than 99.6% identity with M. morganii strain FDAARGOS_172. To our knowledge, this is the first report of fatal fibrinonecrotizing bronchopneumonia associated with M. morganii infection in a cetacean.
Assuntos
Golfinho Nariz-de-Garrafa , Broncopneumonia/veterinária , Infecções por Enterobacteriaceae/veterinária , Morganella morganii/isolamento & purificação , Animais , Broncopneumonia/microbiologia , Broncopneumonia/patologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/patologia , Evolução Fatal , FemininoRESUMO
BACKGROUND: Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. METHODS: We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. RESULTS: In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. CONCLUSION: ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.
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Soro Antilinfocitário , Rejeição de Enxerto , Imunossupressores , Transplante de Rim , Metanálise em Rede , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Alemtuzumab/uso terapêuticoRESUMO
BACKGROUND: Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. METHODS: Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. RESULTS: Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. CONCLUSIONS: We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.
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Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Sobrevivência de Enxerto , Imunossupressores , Transplante de Rim , Metanálise em Rede , Rituximab , Humanos , Sistema ABO de Grupos Sanguíneos/imunologia , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologiaRESUMO
BACKGROUND: Rituximab and plasmapheresis (PP) suppress and eliminate antibody production in patients experiencing antibody-mediated rejection (AMR). Herein, we discuss a case where rituximab was less effective after PP for treating AMR. CASE: A 55-year-old male patient underwent kidney transplantation. His renal function remained normal for 1 year. Subsequently, renal function declined, and (donor-specific antibodies showed positive results. A biopsy of the transplanted kidney revealed AMR. On the day of the biopsy, the medical staff administered 200 mg of rituximab, followed by IV immunoglobulin (IVIg) and PP the next day. The time interval between PP + IVIg treatment and rituximab was 12 h. As a result, the B-cell markers CD19 and CD20 did not decrease sufficiently, and the patient's creatinine and glomerular filtration rate muscles did not recover adequately. CONCLUSION: We report a case in which PP was administered shortly after rituximab injection, resulting in insufficient B-cell inhibition due to the removal of rituximab.
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Rejeição de Enxerto , Transplante de Rim , Plasmaferese , Rituximab , Humanos , Rituximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rejeição de Enxerto/imunologia , Resultado do Tratamento , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacosRESUMO
BACKGROUND: ABO-incompatible (ABOi) transplantation is a novel method transplantation method that carries a heightened risk of infection caused by the use of high immunosuppressant doses. This elevated risk is particularly concerning for viral infections, such as cytomegalovirus (CMV) and the BK virus (BKV) increases. Herein, we present a case where high-dose intravenous immunoglobulin (IVIG) was effective in treating viral infections after transplantation. METHODS: A 41-year-old man underwent an ABOi transplantation. The initial isoagglutinin titer was 1:32. The patient received 200 mg of rituximab, and 3 rounds of plasmapheresis were performed. Subsequently, renal function remained normal; however, 7 months later, the renal function declined, and BK nephropathy and CMV infection were diagnosed through biopsy and serologic tests. The FK level was reduced, and mycophenolate mofetil was discontinued. Although ciprofloxacin and leflunomide were administered, their effects were minimal. Therefore, high-dose IVIG (1 g/kg) was administered 5 times over 5 weeks, which led to a reduction in BK viral load and CMV infectivity in the serum. CONCLUSIONS: High-dose IVIG may serve as a promising alternative treatment to mitigate early transplant rejection and BKV and CMV infections.
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Soro Antilinfocitário , Vírus BK , Infecções por Citomegalovirus , Imunoglobulinas Intravenosas , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Transplante de Rim/efeitos adversos , Masculino , Adulto , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/virologia , Infecções por Citomegalovirus/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Sistema ABO de Grupos Sanguíneos/imunologia , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Incompatibilidade de Grupos SanguíneosRESUMO
Constipation is a highly prevalent gastrointestinal disorder in patients with chronic kidney disease (CKD). However, our understanding of its epidemiology and management in CKD is limited. We aimed to explore real-world data on constipation and laxative use in patients with CKD in a nationwide population-based cohort from the Korean Health Insurance Review and Assessment-National Patient Sample database. This study analyzed retrospective health claims data in Korea from 2012 to 2017 that were transformed into the Observational Medical Outcomes Partnership Common Data Model. The pooled proportion of constipation diagnoses was 30.5% in all patients with CKD and 15.9%, 16.5%, 17.4%, 29.9%, and 43.3% in patients with CKD stages 1-5, respectively, suggesting a higher prevalence in advanced CKD. Patients receiving peritoneal dialysis or hemodialysis had the highest prevalence of constipation, while transplant recipients showed a prevalence comparable to that of patients with early CKD. Patients with CKD had a significantly higher risk of constipation than age- and sex-matched non-CKD individuals (range of odds ratio [OR]:1.66-1.90). Laxative prescribing patterns differed by CKD severity. Osmotic agents were prescribed in more than half of patients with advanced CKD, while magnesium salts and bulking agents were prescribed less frequently. The CKD patients with constipation were more likely to be prescribed constipation-inducing medications, including antipsychotic and neurological medications. Our findings provide real-world constipation and laxative prescription status in the Korean CKD population, revealing a significantly higher risk of constipation and different laxative prescribing patterns in patients with CKD.
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Laxantes , Insuficiência Renal Crônica , Humanos , Laxantes/uso terapêutico , Estudos Retrospectivos , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/tratamento farmacológico , República da Coreia/epidemiologiaRESUMO
BACKGROUND/AIM: Human melanoma-associated antigen A2 (hMAGEA2) family members play several roles in many types of cancer and have been explored as potential prognostic markers. In this study, we investigated the molecular mechanism underlying hMAGEA2-mediated tumorigenesis of prostate cancer. MATERIALS AND METHODS: Immunohistochemistry and western blot were used to assess protein expression whereas microarray and quantitative reverse transcription-PCR determined mRNA expression. CCK-8 assay was used to determine cell proliferation. Colony formation assay was used to examine tumorigenesis. Migration and invasion were examined using a transwell assay. Propidium iodide (PI)/Annexin V double staining was performed to measure apoptosis. Transcriptional activity was measured using Dual-luciferase reporter assay. RESULTS: hMAGEA2 was highly over-expressed in human prostate cancer tissues compared to benign prostatic hyperplasia tissues. To elucidate its biological function in prostate cancer, we established two stable hMAGEA2-knockdown prostate cancer cell lines, PC3M and 22RV1, and found that they presented significantly decreased proliferation, anchorage-independent colony formation, migration, and invasion. As hMAGEA2 knockdown suppressed prostate cancer cell growth, we examined its potential influence on tumor apoptosis. hMAGEA2-knockdown cell lines displayed early apoptosis. Moreover, knockdown of hMAGEA2 resulted in the down-regulation of EFNA3 expression. Luciferase assay showed that hMAGEA2 bound to the EFNA promoter region and regulated its transcription. Down-regulation of EFNA3 expression led to decreased Ras/Braf/MEK/Erk1/2 phosphorylation and, consequently, inhibited prostate cancer progression. CONCLUSION: hMAGEA2 promotes prostate cancer growth, metastasis, and tumorigenesis by regulating the EFNA3-Erk1/2 signaling pathway, indicating its potential as a therapeutic marker for prostate cancer.
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Apoptose , Proliferação de Células , Progressão da Doença , Sistema de Sinalização das MAP Quinases , Neoplasias da Próstata , Humanos , Masculino , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fatores de TranscriçãoRESUMO
BACKGROUND: The main objective of hemodialysis (HD) is to correct the excessive accumulation and abnormal distribution of body fluid. Therefore, changes in the systemic hemodynamic parameters and in the ocular fluid volume and composition can occur during a single HD session. The aim of this study is to evaluate the short-term changes in the ophthalmologic findings after HD. METHODS: Thirty eyes of 30 patients with chronic renal failure (CRF) undergoing HD were analyzed. The subjects were categorized into two groups according to the cause of CRF. Detailed ophthalmologic examinations were performed immediately before and after HD. The relationships between the systemic hemodynamic changes and the ophthalmologic changes during a single HD session were evaluated. RESULTS: The results show that a body fluid correction after HD involves a change in the plasma colloid osmotic pressure. The mean intraocular pressure (IOP) decreased after HD with a mean decrease of 2.4 ± 2.1 mmHg and the central corneal thickness decreased with a mean change of 6.9 ± 5.4 µm. After HD, the ocular surface changed significantly; the tear break-up time (TBUT) and basal tear secretion (Schirmer's test) decreased, whereas the keratoepitheliopathy score increased. The macular thickness measured by spectral domain optical coherence tomography (SD-OCT) decreased after HD. The mean decrease in the central subfield thickness was 7.4 ± 9.9 µm. The ocular surface changes after HD affected the visual acuity and examination quality. A significant correlation was found between the changes in the systemic hemodynamic parameters and those in the ophthalmologic findings, except for the retinal thickness. CONCLUSIONS: The changes in the ophthalmologic findings after HD were consistent and significant in all CRF subjects. These changes correlated with the increase in plasma colloid osmotic pressure. HD can correct the volume and composition of ocular fluid. Therefore, it can affect the ophthalmologic findings in a short period of time. In addition, for good examination quality, it is recommended that an ophthalmologic examination in CRF patients be performed on a non-dialysis day or prior to HD on a dialysis day. Furthermore, for accurate comparison of examination results, the time interval from an HD session to an ophthalmologic examination must be considered.
Assuntos
Córnea/patologia , Pressão Intraocular/fisiologia , Falência Renal Crônica/terapia , Diálise Renal , Retina/patologia , Acuidade Visual/fisiologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Peso Corporal , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Concentração Osmolar , Pressão Osmótica , Tomografia de Coerência ÓpticaRESUMO
An unknown-aged adult female wild boar (Sus scrofa) was brought to Kyungpook National University for postmortem examination. Gross examination revealed gallbladder agenesis. Histologically, the liver was cirrhotic and had intrahepatic cholelithiasis, the choleliths were yellow, brown, gray, and black, and had coffin-lid and pyramidal appearances. Fourier-transform infrared spectroscopy analysis revealed that the components were 80% struvite and 20% calcium oxalate monohydrate. Chronic inflammatory cell infiltration was observed, with hyperplastic hepatocellular nodules characterized by large nuclei, prominent nucleoli, and scant cytoplasm with frequent binucleation, surrounded by thick fibrous septa. The epithelium of intrahepatic bile ducts that contained choleliths had undergone gallbladder-like metaplasia, which might have been induced by chronic irritation from the stones or by the accompanying chronic bacterial infection that was observed in Gram stains.
Assuntos
Colelitíase , Doenças dos Suínos , Feminino , Animais , Suínos , Vesícula Biliar/patologia , Colelitíase/veterinária , Colelitíase/complicações , Colelitíase/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Metaplasia/veterinária , Metaplasia/complicações , Metaplasia/patologia , Sus scrofa , Doenças dos Suínos/patologiaRESUMO
Chronic kidney disease (CKD) progression involves morphological changes in the kidney, such as decreased length and thickness, with associated histopathological alterations. However, the relationship between morphological changes in the kidneys and glomerular filtration rate (GFR) has not been quantitatively and comprehensively evaluated. We evaluated the three-dimensional size and shape of the kidney using computed tomography (CT)-derived features in relation to kidney function. We included 257 patients aged ≥18 years who underwent non-contrast abdominal CT at the Inha University Hospital. The features were quantified using predefined algorithms in the pyRadiomics package after kidney segmentation. All features, except for flatness, significantly correlated with estimated GFR (eGFR). The surface-area-to-volume ratio (SVR) showed the strongest negative correlation (r = -0.75, p < 0.0001). Kidney size features, such as volume and diameter, showed moderate to high positive correlations; other morphological features showed low to moderate correlations. The calculated area under the receiver operating characteristic (ROC) curve (AUC) for different features ranged from 0.51 (for elongation) to 0.86 (for SVR) for different eGFR thresholds. Diabetes patients had weaker correlations between the studied features and eGFR and showed less bumpy surfaces in three-dimensional visualization. We identified alterations in the CKD kidney based on various three-dimensional shape and size features, with their potential diagnostic value.