Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 749
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38961844

RESUMO

Chronic kidney disease (CKD) is associated with renal lipid dysmetabolism among a variety of other pathways. We recently demonstrated that oxysterol-binding protein like 7 (OSBPL7) modulates the expression and function of ATP Binding Cassette Subfamily A Member 1 (ABCA1) in podocytes, a specialized type of cell essential for kidney filtration. Drugs that target OSBPL7 lead to improved renal outcomes in several experimental models of CKD. However, the role of OSBPL7 in podocyte injury remains unclear. Employing mouse models and cellular assays, we investigated the influence of OSBPL7 deficiency on podocytes. We demonstrated that reduced renal OSBPL7 levels as observed in two different models of experimental CKD are linked to increased podocyte apoptosis, primarily mediated by heightened endoplasmic reticulum (ER) stress. While as expected the absence of OSBPL7 also resulted in lipid dysregulation (increased lipid droplets and triglycerides content), OSBPL7-deficiency related lipid dysmetabolism did not contribute to podocyte injury. Similarly, we demonstrated that the decreased autophagic flux we observed in OSBPL7-deficient podocytes was not the mechanistic link between OSBPL7-deficiency and apoptosis. In a complementary zebrafish model, osbpl7 knockdown was sufficient to induce proteinuria and morphological damage to the glomerulus, underscoring its physiological relevance. Our study shed new light on the mechanistic link between OSBPL7 deficiency and podocyte injury in glomerular diseases associated with CKD, and it strengthen the role of OSBPL7 as a novel therapeutic target.

2.
Sci Rep ; 14(1): 16013, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992145

RESUMO

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.


Assuntos
Transtornos da Cefaleia Secundários , Humanos , Masculino , Feminino , Transtornos da Cefaleia Secundários/prevenção & controle , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Estudos Prospectivos , Estudos Transversais , Analgésicos/uso terapêutico , Analgésicos/efeitos adversos , Idoso
3.
Heliyon ; 10(12): e32536, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975104

RESUMO

Objective: The Bárány Society recently established diagnostic criteria for presbyvestibulopathy, an age-related bilateral vestibular impairments in older individuals. Drawing upon a cross-sectional database, this study delves into the demographic and clinical features of presbyvestibulopathy patients and investigates the implications of otolith dysfunction. Methods: The study retrospectively analyzed 1218 patients aged 60 years or older who visited the tertiary dizziness clinic in 2020, due to symptoms of dizziness or instability. By reviewing medical records, we gathered clinical information and laboratory vestibular test results, such as cervical and ocular vestibular evoked myogenic potentials, and subjective visual vertical. Results: Out of 1218 patients aged 60 and above who reported dizziness or unsteadiness, 33 patients (2.7 %, with an average age of 74.2 ± 9.2 years) were diagnosed with presbyvestibulopathy. Deficiencies in horizontal angular vestibulo-ocular reflex were found in caloric tests (75 %), video head impulse tests (51.7 %), and rotatory chair tests (47.8 %), respectively. Otolith dysfunction was also observed, as shown by abnormal ocular and cervical vestibular evoked myogenic potentials in 62.96 % and 51.85 % of patients, and abnormal subjective visual vertical in 45.8 % of the cases. Conclusions: Among elderly patients experiencing consistent dizziness or instability, the incidence of presbyvestibulopathy was approximately 2.7 % over one year. Alongside the abnormalities detected in the horizontal angular vestibulo-ocular reflex, significant changes were also noted in the ocular and cervical vestibular evoked myogenic potentials, as well as in the subjective visual vertical tests. As a result, it's vital to underscore the significance of both otolithic function and vestibulo-ocular reflex in the fundamental mechanisms of presbyvestibulopathy.

4.
J Adv Nurs ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39003658

RESUMO

AIM: To explore the transitional experiences of becoming housed from homelessness. DESIGN: A qualitative descriptive study. METHODS: Data were collected during 2017 and 2018 using a semi-structured interview method with 10 former homeless people who became housed at the time of the study. The grounded theory method was used to analyse qualitative data. RESULTS: 'Desire to keep a place to stretch out and lie down' was the basic social problem participants suffered during the transition from homeless to becoming housed. In addition, 'returning to the social world as a person living an ordinary life' was the basic social process that emerged as a core category. The process was divided into four phases: (1) being discarded from everyday life in the social world, (2) struggling to reconnect with society and (3) returning to the social world as a person living an ordinary life. CONCLUSION: The transition from homelessness to becoming housed is a significant experience for individuals that involves holistic changes. Community health nurses should consider their practical needs based on client views. IMPACT: What problem did the study address? This study explored the experiences of transitioning from homelessness to becoming housed among post-homeless individuals. What were the main findings? While moving from homelessness to becoming housed, homeless people experienced returning to the social world as a person living an ordinary life. They were also shown to go through the process of four stages. Where and on whom will the research have an impact? This study will contribute to suggesting a direction for self-reliance-based interventions among people who are homeless. Additionally, the findings will provide primary data to develop a program for social integration. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

5.
Sci Adv ; 10(27): eadj4433, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38959322

RESUMO

Memory processes rely on a molecular signaling system that balances the interplay between positive and negative modulators. Recent research has focused on identifying memory-regulating genes and their mechanisms. Phospholipase C beta 1 (PLCß1), highly expressed in the hippocampus, reportedly serves as a convergence point for signal transduction through G protein-coupled receptors. However, the detailed role of PLCß1 in memory function has not been elucidated. Here, we demonstrate that PLCß1 in the dentate gyrus functions as a memory suppressor. We reveal that mice lacking PLCß1 in the dentate gyrus exhibit a heightened fear response and impaired memory extinction, and this excessive fear response is repressed by upregulation of PLCß1 through its overexpression or activation using a newly developed optogenetic system. Last, our results demonstrate that PLCß1 overexpression partially inhibits exaggerated fear response caused by traumatic experience. Together, PLCß1 is crucial in regulating contextual fear memory formation and potentially enhancing the resilience to trauma-related conditions.


Assuntos
Giro Denteado , Medo , Memória , Neurônios , Fosfolipase C beta , Animais , Fosfolipase C beta/metabolismo , Fosfolipase C beta/genética , Medo/fisiologia , Giro Denteado/metabolismo , Giro Denteado/fisiologia , Memória/fisiologia , Camundongos , Neurônios/metabolismo , Neurônios/fisiologia , Camundongos Knockout , Masculino , Optogenética , Camundongos Endogâmicos C57BL
6.
Front Oncol ; 14: 1352865, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933440

RESUMO

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

8.
Br J Anaesth ; 133(2): 296-304, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38839471

RESUMO

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).


Assuntos
Anestésicos Inalatórios , Anestésicos Intravenosos , Procedimentos Cirúrgicos Cardíacos , Desflurano , Complicações Pós-Operatórias , Propofol , Humanos , Propofol/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Anestésicos Intravenosos/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Idoso , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Adulto , Sevoflurano/efeitos adversos , Anestesia Intravenosa/métodos , China/epidemiologia , Tempo de Internação/estatística & dados numéricos , Anestesia por Inalação/métodos , Anestesia por Inalação/efeitos adversos , Resultado do Tratamento
9.
Neuroophthalmology ; 48(3): 193-197, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756336

RESUMO

Ma Huang (Ephedra), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.

10.
J Sci Food Agric ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767320

RESUMO

BACKGROUND: Fresh ginseng is typically accompanied by soil after harvest, leading to contamination with harmful fungi during storage and distribution. In this study, we investigated the incidence of fungal contamination in fresh ginseng (5-6 years old) purchased from 22 different stores in Geumsan, Korea. RESULTS: The incidence of fungal contamination in the samples was 67.4-111.5%. Fusarium solani was the most abundant species in the head (38.5%) and fine root (19.3%) parts of the ginseng samples, whereas F. oxysporum was the most abundant in the main root (22.0%) part. We isolated Aspergillus, Fusarium and Penicillium spp. (total number of isolates: 395) from the ginseng samples, and 138 isolates were identified using phylogenetic analysis. Polymerase chain reaction-based screening of 65 mycotoxin-producing species revealed that two P. expansum isolates were positive for citrinin and/or patulin, and five F. oxysporum isolates were positive for fumonisin biosynthesis gene. One P. expansum isolate produced 738.0 mg kg-1 patulin, and the other produced 10.4 mg kg-1 citrinin and 12.0 mg kg-1 patulin on potato dextrose agar (PDA) medium. Among the 47 representative F. oxysporum isolates, 43 (91.5%) produced beauvericin (0.1-15.4 mg kg-1) and four of them (8.5%) produced enniatin B and enniatin B1 (0.1-1.8 mg kg-1) as well. However, none of these toxins was detected in fresh ginseng samples. CONCLUSION: Fusarium solani and F. oxysporum were the most abundant species in fresh ginseng samples. Most F. oxysporum (43) and P. expansum (2) strains isolated from fresh ginseng produced beauvericin and enniatins (B and B1), and patulin or citrinin, respectively, on PDA medium. This is the first report of the mycotoxigenic potential of P. expansum and F. oxysporum strains isolated from fresh ginseng. © 2024 Society of Chemical Industry.

11.
Kidney360 ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781016

RESUMO

BACKGROUND: We previously demonstrated that Empagliflozin (Empa), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduces intrarenal lipid accumulation and slows kidney function decline in experimental Alport syndrome (AS). In this study, we aimed to evaluate the renal protective benefits of Linagliptin (Lina), a dipeptidyl peptidase-4 (DPP4) inhibitor in AS and compare it to Empa. METHODS: Metabolite distribution in kidney cortices was assessed using mass spectrometry imaging. We examined albuminuria and histological changes in kidneys from AS mice treated with Lina and/or Empa or vehicle. RESULTS: Several metabolites, including adrenic acid (AdA) and glucose, were increased in renal cortices of AS mice when compared to wildtype (WT) mice, while eicosapentaenoic acid (EPA) levels were decreased. In addition, a redistribution of AdA from the glomerular compartment in WT mice to the tubulointerstitial compartment in AS mice was observed. Both Lina and Empa treatments were found to reduce albuminuria, to extend the survival of AS mice for about 10 days, and to decrease glomerulosclerosis and tubulointerstitial fibrosis compared to WT mice. There were no significant differences with regard to the renal phenotype observed between Empa and Lina treated AS mice, and the combination of Lina and Empa was not superior to individual treatments. In vitro experiments revealed that DPP4 is expressed in podocytes and tubular cells derived from both AS and WT mice. Differently from what we have reported for Empa, Lina treatment was found to reduce glucose-driven respiration in AS tubular cells, but not in AS podocytes. CONCLUSIONS: Renal expression patterns and spatial distribution of several metabolites differ in AS compared to WT mice. While Lina and Empa treatments similarly partially slow the progression of kidney disease in AS, the metabolic mechanisms conferring the protective effect may be different.

12.
Pediatr Transplant ; 28(4): e14784, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38766976

RESUMO

BACKGROUND: The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA). METHODS: This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment. RESULTS: The median age at HSCT for all 52 patients was 15 years (range 1-25). The 3-year overall survival (OS) by donor type were as follows: 95% [95% CI 85.4-99] for matched related donors (MRD) (N = 24), 84% [95% CI 63.5-99] for haploidentical (N = 13), and 71% [95% CI 36-99] for matched unrelated donors (MUD) (N = 7). The 3-year OS was 81% [95% CI 69.7-99] for all patients, 90.5% [95% CI 79.5-99] for non-IST patients (N = 27), and 70% [95% CI 51-99] for IST patients (N = 24) (log-rank p = .04). Survival of haploidentical HSCT (haplo-HSCT) recipients with post-transplant cyclophosphamide (PTCy) (N = 13) was excellent for both groups: 100% for non-IST patients (N = 3) and 80% for IST patients (N = 10). The 3-year OS for patients with previous IST by donor type in groups where >5 patients were available was 78.8% [95% CI 52.3-99] for haplo-HSCT (N = 10) and 66.7% [95% CI 28.7-99] for MUD (N = 6). Although it appears that patients receiving HSCT ≥6 months after the start of IST had worse survival, the number of patients in each category was small and log-rank was not significant(p = .65). CONCLUSIONS: Patients receiving MUD and haplo-HSCT with PTCy had similar outcomes, suggesting that haplo-HSCT with PTCy could be included in randomized trials of upfront IST versus alternative donor HSCT.


Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Humanos , Anemia Aplástica/terapia , Adolescente , Criança , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Adulto Jovem , Adulto , Lactente , Resultado do Tratamento , Terapia de Imunossupressão/métodos , Doadores de Tecidos , Imunossupressores/uso terapêutico
14.
PLoS One ; 19(4): e0301622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630695

RESUMO

This paper proposes a reinforced concrete (RC) boundary beam-wall system that requires less construction material and a smaller floor height compared to the conventional RC transfer girder system. The structural performance of this system subjected to axial compression was evaluated by performing a structural test on four specimens of 1/2 scale. In addition, three-dimensional nonlinear finite element analysis was also performed to verify the effectiveness of the boundary beam-wall system. Three test parameters such as the lower wall length-to-upper wall length ratio, lower wall thickness, and stirrup details of the lower wall were considered. The load-displacement curve was plotted for each specimen and its failure mode was identified. The test results showed that decrease in the lower wall length-to-upper wall length ratio significantly reduced the peak strength of the boundary beam-wall system and difference in upper and lower wall thicknesses resulted in lateral bending caused by eccentricity in the out-of-plane direction. Additionally, incorporating cross-ties and reducing stirrup spacing in the lower wall significantly improved initial stiffness and peak strength, effectively minimizing stress concentration.


Assuntos
Materiais de Construção , Compressão de Dados , Análise de Elementos Finitos , Fenômenos Físicos
15.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623660

RESUMO

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Estudos Retrospectivos , Predisposição Genética para Doença , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Mutação , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Testes Genéticos/métodos , Proteína BRCA1/genética , Proteína BRCA2/genética
16.
Plant Pathol J ; 40(2): 151-159, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606445

RESUMO

Bacterial soft rot caused by Pectobacterium carotovorum subsp. carotovorum (Pcc) is one of the most severe diseases in radish cultivation. To control this plant disease, the most effective method has been known to cultivate resistant cultivars. Previously, we developed an efficient bioassay method for investigating resistance levels with 21 resistant and moderately resistant cultivars of radish against a strain Pcc KACC 10421. In this study, our research expanded to investigate the resistance of radish cultivars against six Pcc strains, KACC 10225, KACC 10421, ATCC 12312, ATCC 15713, LY34, and ECC 301365. To this end, the virulence of the six Pcc strains was determined based on the development of bacterial soft rot in seedlings of four susceptible radish cultivars. The results showed that the Pcc strains exhibited different virulence in the susceptible cultivars. To explore the race differentiation of Pcc strains corresponding to the resistance in radish cultivars, we investigated the occurrence of bacterial soft rot caused by the six Pcc strains on the 21 resistant and moderate resistant cultivars. Our results showed that the average values of the area under the disease progress curve were positively correlated with the virulence of the strains and the number of resistant cultivars decreased as the virulence of Pcc strains increased. Taken together, our results suggest that the resistance to Pcc of the radish cultivars commercialized in Korea is more likely affected by the virulence of Pcc strains rather than by race differentiation of Pcc.

17.
Artif Cells Nanomed Biotechnol ; 52(1): 250-260, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38687561

RESUMO

Despite many recent studies on non-alcoholic fatty liver disease (NAFLD) therapeutics, the optimal treatment has yet to be determined. In this unfinished project, we combined secondary metabolites (SMs) from the gut microbiota (GM) and Hordeum vulgare (HV) to investigate their combinatorial effects via network pharmacology (NP). Additionally, we analyzed GM or barley - signalling pathways - targets - metabolites (GBSTMs) in combinatorial perspectives (HV, and GM). A total of 31 key targets were analysed via a protein-protein interaction (PPI) network, and JUN was identified as the uppermost target in NAFLD. On a bubble plot, we revealed that apelin signalling pathway, which had the lowest enrichment factor antagonize NAFLD. Holistically, we scrutinized GBSTM to identify key components (GM, signalling pathways, targets, and metabolites) associated with the Apelin signalling pathway. Consequently, we found that the primary GMs (Eubacterium limosum, Eggerthella sp. SDG-2, Alistipes indistinctus YIT 12060, Odoribacter laneus YIT 12061, Paraprevotella clara YIT 11840, Paraprevotella xylaniphila YIT 11841) to ameliorate NAFLD. The molecular docking test (MDT) suggested that tryptanthrin-JUN is an agonist, conversely, dihydroglycitein-HDAC5, 1,3-diphenylpropan-2-ol-NOS1, and (10[(Acetyloxy)methyl]-9-anthryl)methyl acetate-NOS2, which are antagonistic conformers in the apelin signalling pathway. Overall, these results suggest that combination therapy could be an effective strategy for treating NAFLD.


Assuntos
Microbioma Gastrointestinal , Hordeum , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hordeum/microbiologia , Hordeum/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Transdução de Sinais/efeitos dos fármacos , Camundongos , Mapas de Interação de Proteínas , Humanos
18.
Acta Neuropathol Commun ; 12(1): 66, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654316

RESUMO

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.


Assuntos
Apoptose , Camundongos Endogâmicos C57BL , Neurônios , Albumina Sérica , Tauopatias , Animais , Humanos , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Astrócitos/metabolismo , Astrócitos/patologia , Astrócitos/efeitos dos fármacos , Elongases de Ácidos Graxos/metabolismo , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/efeitos dos fármacos , Albumina Sérica/metabolismo , Albumina Sérica/farmacologia , Proteínas tau/metabolismo , Tauopatias/patologia , Tauopatias/metabolismo
19.
Food Sci Biotechnol ; 33(7): 1585-1592, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623426

RESUMO

This research investigated volatiles and odor active compounds in Osmanthus fragrans var. aurantiacus. Heterocyclics were mainly extracted from hexane and dichloromethane extracts. Ketones were mainly detected from butanol fraction, and alcohols were mainly extracted from the ethanol fraction. GC-O analysis investigated the contents and intensities of three major odor active compounds increasing by ramping up polarity Multivariate analysis, which includes principal component analysis (PCA) and hierarchical cluster analysis (HCA), by E-nose data showed 45.83% (PC1) and 29.27 (PC2) variances, respectively, and segregated two clusters. Multivariate analysis by GC-O data showed 65.64% (PC1) and 24.17% (PC2) variances, respectively, and segregated the three clusters, cluster I by ethanol extract, cluster II by dichloromethane extract, and cluster III by hexane and butanol extracts. This study demonstrates that different polarity solvents can collect various volatiles and odor active compound groups. Our findings can support basic research data as a natural and functional food additive.

20.
Cancers (Basel) ; 16(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38473292

RESUMO

Achieving textbook outcomes (TOs) improves the short-term and long-term performance of a hospital. Our objective was to assess TOs in the laparoscopic liver resection (LLR) of tumors in the PS (posterosuperior) section of the liver and identify the impact of the learning curve. We conducted a retrospective cohort study analyzing patients who underwent LLR for lesions located in the PS segments. Patients were divided into a TO and no-TO group. TOs were defined as negative margins, no transfusion, no readmission, no major complications, no 30-day mortality, and a length of stay ≤ 50th percentile. Patients' outcomes were assessed in two study periods before and after 2015. TOs were achieved in 47.6% (n = 117). In multivariable analysis, obesity (p = 0.001), shorter operation time (p < 0.001), less blood loss (p < 0.001), normal albumin (p = 0.003), and minor resection (p = 0.046) were significantly associated with achieving TOs. Although the 5-year recurrence-free survival rate (p = 0.096) was not significantly different, the 5-year overall survival rate was significantly greater in the TO group (p = 0.001). Body mass index > 25 kg/m2 (p = 0.020), age > 65 years (p = 0.049), and achievement of TOs (p = 0.024) were independently associated with survival. The proportion of patients who achieved a TO was higher after 2015 than before 2015 (52.3% vs. 36.1%; p = 0.022). TOs are important markers not only for assessing hospital and surgeon performance but also as predictors of overall survival. As the number of surgeons who achieve the learning curve increases, the number of patients with TOs will gradually increase with a subsequent improvement in overall survival.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA