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1.
Ren Fail ; 46(2): 2403653, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39291665

RESUMEN

Objectives: The aim of this study was to investigate the mechanism of itaconate's potential effect in diabetic kidney disease.Methods: Renal immune responsive gene 1 (IRG1) levels were measured in db/db mice and streptozotocin (STZ) + high-fat diet (HFD)-induced diabetic mice. Irg1 knockout mice were generated. db/db mice were treated with 4-octyl itaconate (4-OI, 50 mg/kg), a derivative of itaconate, for 4 weeks. Renal function and morphological changes were investigated. Ultrastructural alterations were determined by transmission electron microscopy.Results: Renal IRG1 levels were reduced in two diabetic models. STZ+HFD-treated Irg1 knockout mice exhibited aggravated renal tubular injury and worsened renal function. Treatment with 4-OI lowered urinary albumin-to-creatinine ratio and blood urea nitrogen levels, and restored renal histological changes in db/db mice. It improved mitochondrial damage, increased expressions of peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the renal cortex of db/db mice. These were confirmed in vitro; 4-OI improved high glucose-induced abnormal mitochondrial morphology and TFAM expression in HK-2 cells, effects that were inhibited by PGC-1α silencing. Moreover, 4-OI reduced the number of apoptotic cells in the renal cortex of db/db mice. Further study showed that 4-OI increased renal Nrf2 expression and decreased oxidative stress levels in db/db mice. In HK-2 cells, 4-OI decreased high glucose-induced mitochondrial ROS production, which was reversed by Nrf2 silencing. Nrf2 depletion also inhibited 4-OI-mediated regulation of PGC-1α, TFAM, and mitochondrial apoptotic protein expressions.Conclusions: 4-OI attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Ratones Noqueados , Factor 2 Relacionado con NF-E2 , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Succinatos , Animales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Succinatos/farmacología , Succinatos/uso terapéutico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Masculino , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Factores de Transcripción/metabolismo , Túbulos Renales/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/metabolismo , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos
2.
Pestic Biochem Physiol ; 204: 106064, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277381

RESUMEN

Environmental pollution caused by arsenic or its compounds is called arsenic pollution. Arsenic pollution mainly comes from people's mining and smelting of arsenic compounds. In addition, the widespread use of arsenic compounds, such as the use and production of arsenic-containing pesticides, is also a source of arsenic contamination. Arsenic contamination leads to an increased risk of arsenic exposure, and the multi-organ toxicity induced by arsenic exposure is a global health problem. As a non-mammalian vertebrate with high nutrient levels, chickens readily absorb and accumulate arsenic from their food. Relevant studies have shown that arsenic exposure induces hepatotoxicity in chickens, and there has been a steady stream of research into the specific mechanisms involved. PANoptosis, a newly discovered and unique mode of programmed cell death (PCD) characterized by both apoptosis, cellular pyroptosis, and necroptosis. There are no studies to indicate whether chicken liver toxicity due to arsenic is associated with PANoptosis. Therefore, we established chicken animal models and chicken primary hepatocyte models exposed to different arsenic concentrations to dissect the role and mechanism of PANoptosis in arsenic exposure-induced hepatotoxicity in chickens. Our histopathological results showed that arsenic treatment caused dose-dependent damage to chicken liver structure. Meanwhile, different doses of arsenic treatment groups caused significant up-regulation of the protein level of ZBP1, a key factor of PANoptosis. And then consequently triggered the abnormal gene and protein expression levels of apoptosis-associated factors (Caspase-8, Caspase-7, Caspase-3), cellular pyroptosis-associated factors (NLRP3, ASC, GSDMD) and necroptosis-associated factors (RIPK1, RIPK3, MLKL). In conclusion, our study revealed that PANoptosis is involved in arsenic-induced chicken hepatotoxicity. Our findings provide a new perspective on the pathogenesis of arsenic exposure-induced hepatotoxicity in chickens.


Asunto(s)
Arsénico , Pollos , Hígado , Animales , Arsénico/toxicidad , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Necroptosis/efectos de los fármacos , Apoptosis/efectos de los fármacos
3.
BMC Infect Dis ; 24(1): 984, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285314

RESUMEN

BACKGROUND: The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China. METHODS: A cross-sectional study was conducted among 69,667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions. RESULTS: The LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.8% (95%CI, 12.5-13%) and 6.4% (95%CI, 6-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ2 = 2931.9, P < 0.001). CONCLUSIONS: The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions. National screening strategy needs improvement. Regular training and quality assurance could improve the performance of TST and C-TST and close the detection gap of LTBI.


Asunto(s)
Tuberculosis Latente , Tamizaje Masivo , Prueba de Tuberculina , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Estudios Transversales , China/epidemiología , Adolescente , Niño , Masculino , Femenino , Prevalencia , Tamizaje Masivo/métodos , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/diagnóstico
4.
Int J Biol Sci ; 20(11): 4178-4189, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247820

RESUMEN

Currently, chronic hepatitis B virus infection is still one of the most serious public health problems in the world. Though current strategies are effective in controlling infection and slowing down the disease process, it remains a big challenge to achieve a functional cure for chronic hepatitis B in a majority of patients due to the inability to clear the cccDNA pool. The mammalian target of rapamycin (mTOR) integrates nutrition, energy, growth factors, and other extracellular signals, participating in gene transcription, protein translation, ribosome synthesis, and other biological processes. Additionally, mTOR plays an extremely important role in cell growth, apoptosis, autophagy, and metabolism. More and more evidence show that HBV infection can activate the mTOR pathway, suggesting that HBV uses or hijacks the mTOR pathway to facilitate its own replication. Therefore, mTOR signaling pathway may be a key target for controlling HBV infection. However, the role of the central cytokine mTOR in the pathogenesis of HBV infection has not yet been systematically addressed. Notably, mTOR is commonly activated in hepatocellular carcinoma, which can progress from chronic hepatitis B. This review systematically summarizes the role of mTOR in the life cycle of HBV and its impact on the clinical progression of HBV infection.


Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Neoplasias Hepáticas , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virología , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virología , Virus de la Hepatitis B/fisiología , Hepatitis B/metabolismo , Animales , Hepatitis B Crónica/metabolismo
5.
Front Endocrinol (Lausanne) ; 15: 1425101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39229373

RESUMEN

Purpose: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. Methods: A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Results: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). Conclusions: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.


Asunto(s)
Radioisótopos de Yodo , Neoplasias de la Tiroides , Tiroidectomía , Tiroxina , Humanos , Tiroxina/sangre , Tiroxina/administración & dosificación , Tiroxina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/terapia , Radioisótopos de Yodo/uso terapéutico , Radioisótopos de Yodo/administración & dosificación , Adulto , Estudios Retrospectivos , Estudios Prospectivos , Aprendizaje Automático , Tirotropina/sangre , Anciano , Periodo Posoperatorio
6.
Phytochem Anal ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187395

RESUMEN

INTRODUCTION: Astragaloside IV (AS-IV) is an index for the quality evaluation of the traditional Chinese medicine Astragalus and an important material basis for Astragalus to exert its medicinal effects, and it is difficult to obtain a single AS-IV by ordinary separation methods. OBJECTIVE: To find a new isolation method that can prepare AS-IV quickly and efficiently. METHODOLOGY: AS-IV was isolated from Astragalus membranaceus extract by high-speed countercurrent chromatography using a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4.2:0.8:5, v/v) at a speed of 950 rpm at a flow rate of 2 mL/min using one of the high-speed countercurrent chromatographic sequential injection models developed during the previous study. RESULTS: Compared with the common countercurrent chromatographic separation, this separation method increased the injection volume and yield by 4-fold and 4.47-fold, respectively, with only about 1.2-fold increase in solvent consumption and separation time, and the purity was basically not reduced, and 55.9 mg of AS-IV, with a purity of 96.95%, was finally prepared from 400 mg of the crude extract in 240 min. CONCLUSION: The continuous injection mode of high-speed countercurrent chromatography was able to successfully prepare a large amount of AS-IV with high purity at one time.

7.
Org Lett ; 26(33): 7037-7042, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39141560

RESUMEN

α-Silyl alcohols are powerful structural motifs for pharmaceutical chemistry, materials chemistry, and organic synthesis. The limitations of current synthetic techniques encompass a requirement for difficult-to-obtain silyl precursors, noble-metal catalysts, and narrow substrate scopes. Here, we developed a general synthetic method for α-silyl alcohols through electroreductive cross-coupling of aldehydes and chlorosilane. This method features easily available reagents, mild conditions, and a wide substrate scope. The establishment of this protocol will provide an alternative for access to α-silyl alcohols.

8.
CNS Neurosci Ther ; 30(8): e14906, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39118226

RESUMEN

AIMS: Schizophrenia is characterized by alterations in resting-state spontaneous brain activity; however, it remains uncertain whether variations at diverse spatial scales are capable of effectively distinguishing patients from healthy controls. Additionally, the genetic underpinnings of these alterations remain poorly elucidated. We aimed to address these questions in this study to gain better understanding of brain alterations and their underlying genetic factors in schizophrenia. METHODS: A cohort of 103 individuals with diagnosed schizophrenia and 110 healthy controls underwent resting-state functional MRI scans. Spontaneous brain activity was assessed using the regional homogeneity (ReHo) metric at four spatial scales: voxel-level (Scale 1) and regional-level (Scales 2-4: 272, 53, 17 regions, respectively). For each spatial scale, multivariate pattern analysis was performed to classify schizophrenia patients from healthy controls, and a transcriptome-neuroimaging association analysis was performed to establish connections between gene expression data and ReHo alterations in schizophrenia. RESULTS: The ReHo metrics at all spatial scales effectively discriminated schizophrenia from healthy controls. Scale 2 showed the highest classification accuracy at 84.6%, followed by Scale 1 (83.1%) and Scale 3 (78.5%), while Scale 4 exhibited the lowest accuracy (74.2%). Furthermore, the transcriptome-neuroimaging association analysis showed that there were not only shared but also unique enriched biological processes across the four spatial scales. These related biological processes were mainly linked to immune responses, inflammation, synaptic signaling, ion channels, cellular development, myelination, and transporter activity. CONCLUSIONS: This study highlights the potential of multi-scale ReHo as a valuable neuroimaging biomarker in the diagnosis of schizophrenia. By elucidating the complex molecular basis underlying the ReHo alterations of this disorder, this study not only enhances our understanding of its pathophysiology, but also pave the way for future advancements in genetic diagnosis and treatment of schizophrenia.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Neuroimagen , Esquizofrenia , Transcriptoma , Humanos , Esquizofrenia/genética , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/metabolismo , Femenino , Masculino , Adulto , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Neuroimagen/métodos , Análisis Multivariante , Adulto Joven , Persona de Mediana Edad , Estudios de Cohortes , Biomarcadores/metabolismo
9.
Food Sci Nutr ; 12(8): 5426-5441, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139945

RESUMEN

Golden buckwheat, also called Fagopyrum dibotrys (D. Don) H. Hara, is a plant of the genus Buckwheat in the buckwheat family. The aim of this study was to screen the bioactive ingredients of golden buckwheat extract and investigate the protective effect on acute lung injury (ALI). The ethyl acetate extract (EAE) was identified as the active fraction in LPS-induced RAW264.7 cells, with gallic acid, proanthocyanidin B2, and epicatechin at 0.0563%, 0.3707%, and 0.3868%, respectively. At the same time, 20 compounds (mainly flavonoids and organic acids) were identified by UPLC-Q-Exactive Orbitrap-HRMS in EAE. Furthermore, the EAE reduced lung histopathology scores in mice with ALI, decreased the dry-to-wet weight ratio of lung tissue, and significantly inhibited the concentrations of IL-1ß, TNFα, and IL-6 in bronchoalveolar lavage fluid (BALF). It also reduced the number of leukocytes, decreased the activity of MPO in lung tissue, and inhibited the levels of TLR4/NLRP3 pathway mRNA and protein in lung tissue. Our study indicated that golden buckwheat as a source of functional food prevents or treats associated lung diseases by modulating the activation of the TLR4/NLRP3 signaling pathway.

10.
Genome Biol ; 25(1): 232, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198826

RESUMEN

BACKGROUND: The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. RESULTS: To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. CONCLUSIONS: Our study underscores the importance of Blautia A species in the gut microbiota's rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.


Asunto(s)
Aclimatación , Altitud , Microbioma Gastrointestinal , Hipoxia , Humanos , Animales , Adulto , Masculino , Hipoxia/genética , Ratones , Femenino , Estudios Longitudinales , Mal de Altura/microbiología , Mal de Altura/genética , Persona de Mediana Edad
11.
Environ Sci Technol ; 58(35): 15790-15798, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39172077

RESUMEN

In this study, various crops and farmland soils were collected from the Fen-Wei Plain, China, to investigate the bioavailability of perfluoroalkyl substances (PFAS), their accumulation in edible plant tissues, and the factors impacting their accumulation. PFAS were frequently detected in all of the crops, with total concentrations ranging from 0.61 to 35.8 ng/g. The results of sequential extractions with water, basic methanol, and acidic methanol indicate that water extraction enables to characterize the bioavailability of PFAS in soil to edible plant tissues more accurately, especially for the shorter-chain homologues. The bioavailability of PFAS was remarkably enhanced in the rhizosphere (RS) soil, with the strongest effect observed for leafy vegetables. The water-extracted Σ16PFAS in RS soil was strongly correlated with the content of dissolved organic carbon in the soil. Tannins and lignin, identified as the main components of plant root exudates by Fourier transform-ion cyclotron resonance mass spectrometry, were found to enhance the bioavailability of PFAS significantly. Redundancy analysis provided strong evidence that the lipid and protein contents in edible plant tissues play important roles in the accumulation of short- and long-chain PFAS, respectively. Additionally, the high water demand of these tissues during the growth stage greatly facilitated the translocation of PFAS, particularly for the short-chain homologues and perfluorooctanoic acid.


Asunto(s)
Contaminantes del Suelo , Suelo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/farmacocinética , Suelo/química , Plantas Comestibles/química , Plantas Comestibles/metabolismo , Fluorocarburos/metabolismo , China , Granjas , Disponibilidad Biológica
12.
Nat Commun ; 15(1): 5521, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951553

RESUMEN

The microgeometry of the cellular microenvironment profoundly impacts cellular behaviors, yet the link between it and the ubiquitously expressed mechanosensitive ion channel PIEZO1 remains unclear. Herein, we describe a fluorescent micropipette aspiration assay that allows for simultaneous visualization of intracellular calcium dynamics and cytoskeletal architecture in real-time, under varied micropipette geometries. By integrating elastic shell finite element analysis with fluorescent lifetime imaging microscopy and employing PIEZO1-specific transgenic red blood cells and HEK cell lines, we demonstrate a direct correlation between the microscale geometry of aspiration and PIEZO1-mediated calcium signaling. We reveal that increased micropipette tip angles and physical constrictions lead to a significant reorganization of F-actin, accumulation at the aspirated cell neck, and subsequently amplify the tension stress at the dome of the cell to induce more PIEZO1's activity. Disruption of the F-actin network or inhibition of its mobility leads to a notable decline in PIEZO1 mediated calcium influx, underscoring its critical role in cellular mechanosensing amidst geometrical constraints.


Asunto(s)
Actinas , Calcio , Citoesqueleto , Canales Iónicos , Mecanotransducción Celular , Humanos , Canales Iónicos/metabolismo , Actinas/metabolismo , Células HEK293 , Citoesqueleto/metabolismo , Calcio/metabolismo , Señalización del Calcio/fisiología , Análisis de Elementos Finitos , Animales , Microscopía Fluorescente/métodos
13.
J Nanobiotechnology ; 22(1): 363, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910248

RESUMEN

Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in terms of functionality and practicality. We specifically explore how these innovations have propelled forward the analysis of thrombocytes (platelets), erythrocytes (red blood cells) and leukocytes (white blood cells), shedding light on the nanoscale arrangement of subcellular components and molecular interactions. We spotlight novel biomarkers uncovered by fluorescence nanoscopy for disease diagnosis, such as thrombocytopathies, malignancies, and infectious diseases. Furthermore, we discuss the technological hurdles and chart out prospective avenues for future research directions. This review aims to underscore the significant contributions of fluorescence nanoscopy to the field of blood cell analysis and disease diagnosis, poised to revolutionize our approach to exploring, understanding, and managing disease at the molecular level.


Asunto(s)
Células Sanguíneas , Microscopía Fluorescente , Animales , Humanos , Células Sanguíneas/ultraestructura , Plaquetas/metabolismo , Eritrocitos , Hematología/métodos , Leucocitos/metabolismo , Microscopía Fluorescente/métodos , Nanotecnología/métodos
14.
Haemophilia ; 30(4): 1050-1058, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38923219

RESUMEN

INTRODUCTION: Total joint replacement is the optimal treatment option for patients with severe haemophilic arthritis. Current research emphasizes patient-reported outcomes as a vital measure for evaluating surgical outcomes and patient satisfaction. Nevertheless, very limited information about the subjective experience of perioperative haemophiliacs in the literature, highlighting the need for exploration in this area. AIM: To investigate the psychological experiences and health demands of haemophilic arthropathy patients during the perioperative period of total joint replacement. DESIGN: Qualitative descriptive research with semistructured individual interviews. METHODS: From June to September 2023, nine patients with severe haemophilic arthropathy who underwent total joint replacement at a Haemophilia Diagnosis and Treatment Centre in China were interviewed for average 37 min per person. Data were analysed using the traditional content analysis method and reported following the consolidated criteria for reporting qualitative research. The study is reported according to the COREQ checklist. RESULTS: Interviews described two main themes: (1) emotional decline which involves preoperative overoptimism, early postoperative anxiety and disease uncertainty during the early independent rehabilitation. (2) wellness aspiration which includes rehabilitation support and spiritual healing. CONCLUSION: This study reveals the patients' significant psychological changes and their well-being aspiration, particularly out-of-hospital rehabilitation needs. Strengthening communication between multidisciplinary teams and patients, enhancing the involvement of nurses, broadening the scope of functions at primary Haemophilia Treatment Centres, and developing telerehabilitation, these concerted efforts may improve the overall treatment experience for patients.


Asunto(s)
Hemofilia A , Investigación Cualitativa , Humanos , Hemofilia A/complicaciones , Hemofilia A/psicología , Masculino , Adulto , Persona de Mediana Edad , Artroplastia de Reemplazo/psicología , Femenino , Periodo Perioperatorio/psicología , Satisfacción del Paciente , Hemartrosis/etiología
15.
Int J Mol Sci ; 25(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38892073

RESUMEN

Xanthomonas oryzae pv. oryzicola (Xoc) is a notorious plant pathogen. Like most bacterial pathogens, Xoc has evolved a complex regulatory network to modulate the expression of various genes related to pathogenicity. Here, we have identified TfmR, a transcriptional regulator belonging to the TetR family, as a key player in the virulence mechanisms of this phytopathogenic bacterium. We have demonstrated genetically that tfmR is involved in the hypersensitive response (HR), pathogenicity, motility and extracellular polysaccharide production of this phytopathogenic bacterium. Our investigations extended to exploring TfmR's interaction with RpfG and HrpX, two prominent virulence regulators in Xanthomonas species. We found that TfmR directly binds to the promoter region of RpfG, thereby positively regulating its expression. Notably, constitutive expression of RpfG partly reinstates the pathogenicity compromised by TfmR-deletion mutants. Furthermore, our studies revealed that TfmR also exerts direct positive regulation on the expression of the T3SS regulator HrpX. Similar to RpfG, sustained expression of HrpX partially restores the pathogenicity of TfmR-deletion mutants. These findings underscore TfmR's multifaceted role as a central regulator governing key virulence pathways in Xoc. Importantly, our research sheds light on the intricate molecular mechanisms underlying the regulation of pathogenicity in this plant pathogen.


Asunto(s)
Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Enfermedades de las Plantas , Regiones Promotoras Genéticas , Factores de Transcripción , Xanthomonas , Xanthomonas/patogenicidad , Xanthomonas/genética , Xanthomonas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Virulencia/genética , Enfermedades de las Plantas/microbiología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Oryza/microbiología
16.
Adv Sci (Weinh) ; 11(32): e2401712, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38900084

RESUMEN

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.


Asunto(s)
Diferenciación Celular , Ensamble y Desensamble de Cromatina , Neoplasias de la Tiroides , Factores de Transcripción , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Humanos , Diferenciación Celular/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ensamble y Desensamble de Cromatina/genética , Ratones , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Transición Epitelial-Mesenquimal/genética , Proliferación Celular/genética , Modelos Animales de Enfermedad
17.
Transl Pediatr ; 13(5): 748-759, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38840687

RESUMEN

Background: Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and metabolism of lipids play a critical role in normal lung development, such as dipalmitoylphosphatidylcholine, a key component of pulmonary surfactant (PS). Therefore, we conducted a lipidomics study of rat lung tissue to explore the changes of pulmonary lipid composition in the progression of BPD disease. Methods: In this study, we exposed neonatal Sprague-Dawley (SD) rats to hyperoxia for 14 days. After hyperoxia exposure, the lung tissues of rats were analyzed pathologically, and untargeted lipidomics was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Hematoxylin-eosin (H&E) staining showed that the alveoli enlarged, the number of alveoli decreased and the pulmonary surfactant-associated protein D (SFTPD) decreased in hyperoxia-exposed rats. A total of 620 pulmonary lipids were detected by LC-MS/MS, covering 27 lipid categories. The most common lipids were triacylglycerol (TAG), followed by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Conclusions: Compared with those rats exposed to normoxic conditions, the lipid levels in the lungs of rats exposed to hyperoxia for 14 days generally decreased, with the levels of TAG and PC decreasing most significantly. In short, our results provide a clue for finding therapeutic targets and biomarkers of a BPD rat model lung liposome.

18.
Int J Biochem Cell Biol ; 172: 106587, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38740281

RESUMEN

Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care, the pathogenesis of which potentially involves altered lipid metabolism. Given the critical role of lipids in lung development and the injury response, we hypothesized that specific lipid species could serve as therapeutic agents in BPD. This study aimed to investigate the role of the lipid Phosphatidylcholine (PC) (16:0/14:0) in modulating BPD pathology and to elucidate its underlying mechanisms of action. Our approach integrated in vitro and in vivo methodologies to assess the effects of PC (16:0/14:0) on the histopathology, cellular proliferation, apoptosis, and molecular markers in lung tissue. In a hyperoxia-induced BPD rat model, we observed a reduction in alveolar number and an enlargement in alveolar size, which were ameliorated by PC (16:0/14:0) treatment. Correspondingly, in BPD cell models, PC (16:0/14:0) intervention led to increased cell viability, enhanced proliferation, reduced apoptosis, and elevated surfactant protein C (SPC) expression. RNA sequencing revealed significant gene expression differences between BPD and PC (16:0/14:0) treated groups, with a particular focus on Cldn1 (encoding claudin 1), which was significantly enriched in our analysis. Our findings suggest that PC (16:0/14:0) might protect against hyperoxia-induced alveolar type II cell damage by upregulating CLDN1 expression, potentially serving as a novel therapeutic target for BPD. This study not only advances our understanding of the role of lipids in BPD pathogenesis, but also highlights the significance of PC (16:0/14:0) in the prevention and treatment of BPD, offering new avenues for future research and therapeutic development.


Asunto(s)
Células Epiteliales Alveolares , Displasia Broncopulmonar , Claudina-1 , Hiperoxia , Fosfatidilcolinas , Regulación hacia Arriba , Animales , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patología , Displasia Broncopulmonar/etiología , Hiperoxia/metabolismo , Hiperoxia/complicaciones , Hiperoxia/patología , Ratas , Claudina-1/metabolismo , Claudina-1/genética , Fosfatidilcolinas/metabolismo , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Ratas Sprague-Dawley , Apoptosis , Proliferación Celular , Humanos , Alveolos Pulmonares/patología , Alveolos Pulmonares/metabolismo , Animales Recién Nacidos , Modelos Animales de Enfermedad
19.
Molecules ; 29(10)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38792169

RESUMEN

Constructive defect engineering has emerged as a prominent method for enhancing the performance of photocatalysts. The mechanisms of the influence of defect types, concentrations, and distributions on the efficiency, selectivity, and stability of CO2 reduction were revealed for this paper by analyzing the effects of different types of defects (e.g., metallic defects, non-metallic defects, and composite defects) on the performance of photocatalysts. There are three fundamental steps in defect engineering techniques to promote photocatalysis, namely, light absorption, charge transfer and separation, and surface-catalyzed reactions. Defect engineering has demonstrated significant potential in recent studies, particularly in enhancing the light-harvesting, charge separation, and adsorption properties of semiconductor photocatalysts for reducing processes like carbon dioxide reduction. Furthermore, this paper discusses the optimization method used in defect modulation strategy to offer theoretical guidance and an experimental foundation for designing and preparing efficient and stable photocatalysts.

20.
Org Lett ; 26(21): 4427-4432, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38757832

RESUMEN

2,3-Diaryl propanoic acids are important structures as a result of their widespread presence in numerous bioactive compounds. However, the limitations of existing synthetic techniques include the requirement for costly catalysts and limited substrates. Here, we developed a novel electroreductive arylcarboxylation of alkenes with CO2 based on a radical-polar crossover pathway assisted by easily accessible dimethyl terephthalate as a reductive mediator. This method will provide an efficient strategy for the synthesis of 2,3-diarylpropanoic acids.

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