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1.
Lab Med ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39005192

RESUMO

BACKGROUND: Distinguishing between different types of pleural effusions (PEs) is crucial for clinical diagnosis and treatment. This study evaluates the diagnostic value of carcinoembryonic antigen (CEA) and interferon-gamma (IFN-γ) levels in PE and serum, as well as the PE/serum ratios of these markers, in classifying PE. METHODS: We retrospectively analyzed 99 patients with PE, categorizing them into malignant pleural effusion (MPE), tuberculous pleural effusion (TPE), and benign PE groups. Levels of CEA and IFN-γ in PE and serum were quantified and their ratios were calculated. Diagnostic performance was assessed using receiver operating characteristic analysis, focusing on the area under the curve (AUC) to determine the efficacy of these biomarkers. RESULTS: Significantly elevated levels of CEA in PE and serum were observed in the MPE group compared to the benign and TPE groups, with the PE/serum CEA ratio offering substantial diagnostic value (AUCs: PE = 0.843, serum = 0.744). Conversely, IFN-γ levels in PE and serum were markedly higher in the TPE group, demonstrating notable diagnostic accuracy (AUCs: PE = 0.970, serum = 0.917). CONCLUSION: Both CEA and IFN-γ demonstrate high clinical utility in differentiating between MPE and TPE. The PE/serum ratio of these biomarkers enhances diagnostic accuracy, potentially facilitating earlier and more accurate therapeutic interventions.

2.
Heliyon ; 10(11): e32117, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38947452

RESUMO

Background: The current prophylactic tuberculosis vaccine Bacille Calmette-Guérin (BCG), was derived in the 1920s, but the humoral immune responses induced by BCG vaccination have not been fully elucidated to date. In this study, our aim was to reveal the profiles of antibody responses induced by BCG vaccination in adults and identify the potential biomarkers for evaluating the BCG vaccination response. Methods: Proteome microarrays were performed to reveal the serum profiles of antibody responses induced by BCG vaccination in adults. ELISA was used to validate the potential biomarkers in validation cohort (79 healthy controls and 58 BCG-vaccinated subjects). Then combined panel was established by logistic regression analysis based on OD values of potential biomarkers. Results: Multiple antigens elicited stronger serum IgG or IgM antibody responses in BCG vaccinated subjects than healthy subjects at 12 weeks post BCG vaccination; among the antigens, Rv0060, Rv2026c and Rv3379c were further verified using 137 serum samples and presented the moderate performance in assessment of the BCG vaccination response by receiver operating characteristic analysis. Furthermore, a combined panel exhibited an improved AUC of 0.923, and the sensitivity and specificity were 77.59 % and 91.14 %, respectively. In addition, the antibody response against Rv0060, Rv2026c and Rv3379c was related to the clinical background to a certain extent. Conclusions: The novel antigens identified in our study could offer better knowledge towards developing a more efficacious vaccine based on humoral immune responses, and they could be potential biomarkers in assessments of BCG vaccination responses.

3.
Cell Death Discov ; 10(1): 323, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009585

RESUMO

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/-) mice did not show any significant changes in body weight or composition. However, Fadd+/- mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/- mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

4.
Int Urol Nephrol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955940

RESUMO

PURPOSE: This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture. METHODS: The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman's correlation analysis was executed to assess the findings. RESULTS: The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 min. The mean intraoperative length of urethral stricture was determined to be 14.4 ± 8.4 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.1 ± 7.5 mm and 13.4 ± 7.2 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman's correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.870 vs. 0.820). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives. CONCLUSIONS: The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application.

5.
Cell Prolif ; : e13702, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956970

RESUMO

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

6.
Chem Commun (Camb) ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957034

RESUMO

A mild and efficient electrochemical method for radical addition, cyclization, and migration reaction was described in this work. A difluoromethyl radical was produced by anodizing CF2HSO2Na. The resulting product was then added to olefin, underwent Smiles cyclization, and migrated to form ß-difluoromethamide compounds after the release of SO2. The process was free from metals and catalysts, gram-grade, and resistant to a variety of electron-rich substrates.

7.
World J Exp Med ; 14(2): 90481, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38948414

RESUMO

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

8.
Front Med ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907157

RESUMO

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), N4-acetylcytidine (ac4C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m6A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

9.
BMC Psychiatry ; 24(1): 452, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890607

RESUMO

BACKGROUND: Getting lost with family members who have dementia is a significant source of stress for family caregivers. In Taiwan, family caregivers develop strategies to deal with dementia persons who may get lost. This study aimed to explore the experiences of family caregivers caring for persons with dementia who have been lost outside the home. METHODS: A descriptive phenomenological method was used. The COREQ checklist was used to ensure the explicit reporting of data. A total of 20 family caregivers caring for persons with dementia who were lost outside their homes were selected from hospital outpatient clinics and a day care center in northern Taiwan using purposive sampling. Data were analyzed using the Giorgi analysis method. RESULTS: Five main themes emerged: (i) surprised persons with dementia lost outside, (ii) using strategies to prevent persons with dementia from getting lost, (iii) using strategies to find lost persons with dementia, (iv) exhaustion in long-term care persons with dementia, and (v) coping with the care load. It was found that family caregivers were surprised, nervous, and worried about persons with dementia being lost outside. They used the first strategy to supervise persons with dementia to prevent external losses. In addition, long-term supervision of persons with dementia led to mental exhaustion in the family caregivers. Finally, the family caregivers learned about loss prevention strategies and obtained family support and care replacement workers to reduce the care burden. CONCLUSIONS: It is essential to teach family caregivers early to prevent persons with dementia from losing external strategies. Nurses also provide long-term care services to reduce the care burden on family caregivers.


Assuntos
Adaptação Psicológica , Cuidadores , Demência , Pesquisa Qualitativa , Humanos , Cuidadores/psicologia , Demência/enfermagem , Demência/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Taiwan , Família/psicologia , Adulto , Estresse Psicológico/psicologia , Idoso de 80 Anos ou mais
10.
World J Clin Cases ; 12(16): 2831-2836, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38899307

RESUMO

BACKGROUND: Computed tomography (CT) small bowel three-dimensional (3D) reconstruction is a powerful tool for the diagnosis of small bowel disease and can clearly show the intestinal lumen and wall as well as the outside structure of the wall. The horizontal axis position can show the best adjacent intestinal tube and the lesion between the intestinal tubes, while the coronal position can show the overall view of the small bowel. The ileal end of the localization of the display of excellent, and easy to quantitative measurement of the affected intestinal segments, the sagittal position for the rectum and the pre-sacral lesions show the best, for the discovery of fistulae is also helpful. Sagittal view can show rectal and presacral lesions and is useful for fistula detection. It is suitable for the assessment of inflammatory bowel disease, such as assessment of disease severity and diagnosis and differential diagnosis of the small bowel and mesenteric space-occupying lesions as well as the judgment of small bowel obstruction points. CASE SUMMARY: Bleeding caused by small intestinal polyps is often difficult to diagnose in clinical practice. This study reports a 29-year-old male patient who was admitted to the hospital with black stool and abdominal pain for 3 months. Using the combination of CT-3D reconstruction and capsule endoscopy, the condition was diagnosed correctly, and the polyps were removed using single-balloon enteroscopy-endoscopic retrograde cholangiopancreatography without postoperative complications. CONCLUSION: The role of CT-3D in gastrointestinal diseases was confirmed. CT-3D can assist in the diagnosis and treatment of gastrointestinal diseases in combination with capsule endoscopy and small intestinal microscopy.

11.
Biomed Phys Eng Express ; 10(4)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38861951

RESUMO

Objective.We aim to: (1) quantify the benefits of lung sparing using non-adaptive magnetic resonance guided stereotactic body radiotherapy (MRgSBRT) with advanced motion management for peripheral lung cancers compared to conventional x-ray guided SBRT (ConvSBRT); (2) establish a practical decision-making guidance metric to assist a clinician in selecting the appropriate treatment modality.Approach.Eleven patients with peripheral lung cancer who underwent breath-hold, gated MRgSBRT on an MR-guided linear accelerator (MR linac) were studied. Four-dimensional computed tomography (4DCT)-based retrospective planning using an internal target volume (ITV) was performed to simulate ConvSBRT, which were evaluated against the original MRgSBRT plans. Metrics analyzed included planning target volume (PTV) coverage, various lung metrics and the generalized equivalent unform dose (gEUD). A dosimetric predictor for achievable lung metrics was derived to assist future patient triage across modalities.Main results.PTV coverage was high (median V100% > 98%) and comparable for both modalities. MRgSBRT had significantly lower lung doses as measured by V20 (median 3.2% versus 4.2%), mean lung dose (median 3.3 Gy versus 3.8 Gy) and gEUD. Breath-hold, gated MRgSBRT resulted in an average reduction of 47% in PTV volume and an average increase of 19% in lung volume. Strong correlation existed between lung metrics and the ratio of PTV to lung volumes (RPTV/Lungs) for both modalities, indicating that RPTV/Lungsmay serve as a good predictor for achievable lung metrics without the need for pre-planning. A threshold value of RPTV/Lungs< 0.035 is suggested to achieve V20 < 10% using ConvSBRT. MRgSBRT should otherwise be considered if the threshold cannot be met.Significance.The benefits of lung sparing using MRgSBRT were quantified for peripheral lung tumors; RPTV/Lungswas found to be an effective predictor for achievable lung metrics across modalities. RPTV/Lungscan assist a clinician in selecting the appropriate modality without the need for labor-intensive pre-planning, which has significant practical benefit for a busy clinic.


Assuntos
Tomografia Computadorizada Quadridimensional , Neoplasias Pulmonares , Pulmão , Imageamento por Ressonância Magnética , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiocirurgia/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Pulmão/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada Quadridimensional/métodos , Masculino , Feminino , Radioterapia Guiada por Imagem/métodos , Suspensão da Respiração , Idoso , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco
12.
Diagnostics (Basel) ; 14(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893636

RESUMO

Our study optimized METex14 skipping mutation detection by analyzing 223 Oncomine™ Focus Assay-positive cases using Pan Lung Cancer PCR Panel and reverse transcription (RT)-PCR. Among the 11 METex14 skipping mutation-positive cases (average read counts: 1390), 2 with Oncomine™ Focus Assay read counts of 2540 and 10,177 were positive on all platforms. Those with Oncomine™ Focus Assay read counts ranging from 179 to 612 tested negative elsewhere. Specimens with low ratios (average ratio: 0.12% for nine cases) may yield false-positive results. Our results suggested that monitoring read counts and ratios and validating the results with RT-PCR are crucial to prevent false positives.

13.
BMJ ; 385: e077890, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38897625

RESUMO

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.


Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gencitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Adulto , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Idoso , Intervalo Livre de Progressão , China , Metástase Neoplásica
14.
Am J Clin Oncol ; 47(7): 333-338, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38775180

RESUMO

OBJECTIVES: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement. METHODS: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure. RESULTS: Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P =0.02), KPS (HR: 0.10, P =0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P <0.01), and use of intrathecal chemotherapy (HR: 0.03, P <0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P =0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT ( P =0.37), Rituximab ( P =0.12), or attempted gross total resection ( P =0.72). CONCLUSIONS: Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification.


Assuntos
Neoplasias do Sistema Nervoso Central , Falha de Tratamento , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/mortalidade , Adulto , Progressão da Doença , Idoso de 80 Anos ou mais , Terapia de Salvação
15.
Autophagy ; : 1-13, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38762760

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) nonstructural protein (NSs) is an important viral virulence factor that sequesters multiple antiviral proteins into inclusion bodies to escape the antiviral innate immune response. However, the mechanism of the NSs restricting host innate immunity remains largely elusive. Here, we found that the NSs induced complete macroautophagy/autophagy by interacting with the CCD domain of BECN1, thereby promoting the formation of a BECN1-dependent autophagy initiation complex. Importantly, our data showed that the NSs sequestered antiviral proteins such as TBK1 into autophagic vesicles, and therefore promoted the degradation of TBK1 and other antiviral proteins. In addition, the 8A mutant of NSs reduced the induction of BECN1-dependent autophagy flux and degradation of antiviral immune proteins. In conclusion, our results indicated that SFTSV NSs sequesters antiviral proteins into autophagic vesicles for degradation and to escape antiviral immune responses.

16.
Zool Res ; 45(3): 663-678, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38766748

RESUMO

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment. Davunetide, an active fragment of the activity-dependent neuroprotective protein (ADNP), has been implicated in social and cognitive protection. However, the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood. In this study, ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice. The neuropathological basis was also explored using Golgi staining, morphological analysis, western blotting, electrophysiological analysis, and behavioral analysis. Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane. In adulthood, anterior cingulate cortex (ACC) neurons exposed to sevoflurane exhibited a decrease in dendrite number, total dendrite length, and spine density. Furthermore, the expression levels of Homer, PSD95, synaptophysin, and vglut2 were significantly reduced in the sevoflurane group. Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Notably, davunetide significantly ameliorated the synaptic defects, social behavior deficits, and cognitive impairments induced by sevoflurane. Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca 2+ activity via the Wnt/ß-catenin signaling, resulting in decreased expression of synaptic proteins. Suppression of Wnt signaling was restored in the davunetide-treated group. Thus, ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.


Assuntos
Animais Recém-Nascidos , Disfunção Cognitiva , Proteoma , Sevoflurano , Comportamento Social , Animais , Sevoflurano/efeitos adversos , Camundongos , Disfunção Cognitiva/induzido quimicamente , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/toxicidade , Anestésicos Inalatórios/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Masculino , Comportamento Animal/efeitos dos fármacos
17.
BMC Anesthesiol ; 24(1): 171, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714926

RESUMO

BACKGROUND: Older critically ill patients experience rapid muscle loss during stay in an intensive care unit (ICU) due to physiological stress and increased catabolism. This may lead to increased ICU length of stay, delayed weaning from ventilation and persistent functional limitations. We hypothesized that with optimal nutrition and early physical therapy acting in synergism, we can reduce muscle mass loss and improve functional outcomes. METHODS: This was a prospective, single blinded randomized, controlled single-center pilot study to compare the lean muscle mass (measured at bilateral quadriceps femoris using ultrasound) of older ICU patients at 4 time points over 14 days between the control and intervention groups. The control group received standard weight-based empiric feeding and standard ICU physiotherapy. The intervention group received indirect calorimetry directed feeding adjusted daily and 60 min per day of cycle ergometry. 21 patients were recruited and randomized with 11 patients in the control arm and 10 patients in the intervention arm. Secondary outcome measures included ICU and hospital mortality, length of stay, functional assessments of mobility and assessment of strength. RESULTS: Median age was 64 in the control group and 66 in the intervention group. Median calories achieved was 24.5 kcal/kg per day in the control group and 23.3 kcal/kg per day in the intervention group. Cycle ergometry was applied to patients in the intervention group for a median of 60 min a day and a patient had a median of 8.5 sessions in 14 days. Muscle mass decreased by a median of 4.7cm2 in the right quadriceps femoris in the control group and 1.8cm2 in the intervention group (p = 0.19), while the left quadriceps femoris decreased by 1.9cm2 in the control group and 0.1cm2 in the intervention group (p = 0.51). CONCLUSION: In this pilot study, we found a trend towards decrease muscle loss in bilateral quadriceps femoris with our combined interventions. However, it did not reach statistical significance likely due to small number of patients recruited in the study. However, we conclude that the intervention is feasible and potentially beneficial and may warrant a larger scale study to achieve statistical significance. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov on 30th May 2018 with identifier NCT03540732.


Assuntos
Calorimetria Indireta , Unidades de Terapia Intensiva , Tempo de Internação , Humanos , Projetos Piloto , Masculino , Idoso , Feminino , Calorimetria Indireta/métodos , Estudos Prospectivos , Pessoa de Meia-Idade , Método Simples-Cego , Estado Terminal/terapia , Ciclismo/fisiologia , Ingestão de Energia/fisiologia , Músculo Quadríceps , Mortalidade Hospitalar
18.
Phytochemistry ; 224: 114140, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38750709

RESUMO

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.


Assuntos
Alcaloides , Fritillaria , Raízes de Plantas , Fritillaria/química , Raízes de Plantas/química , Estrutura Molecular , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Cevanas/química , Cevanas/farmacologia , Cevanas/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Animais , Conformação Molecular , Cristalografia por Raios X , Linhagem Celular , Ratos , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Modelos Moleculares
19.
PhytoKeys ; 241: 131-141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690579

RESUMO

This study provides detailed description of a newly-discovered Callicarpayongshunensis Wen B. Xu, Xiao D. Li & Yan Ling Liu (Lamiaceae) species from Hunan, China. The species shares similarities in the inflorescence, glandular colour and leaf shape features with C.luteopunctata H. T. Chang and C.giraldii Hesse ex Rehd., while its white fruits are similar to those of C.longifolia Lamk. However, its procumbent, evergreen shrub and white fruits are distinctly different from those of C.luteopunctata and C.giraldii, while its procumbent, scarless nodes and stellate pubescence free fruits distinguishes it from C.longifolia. Images, distribution, morphological features, molecular phylogenetic classification and conservation assessment of this new Callicarpa species are explored.

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