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1.
J Palliat Care ; 38(1): 17-23, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34918559

RESUMO

BACKGROUND: Hospice care for end-of-life patients in the ICU should focus on quality of life. Currently, there are no specific quality-of-life measures for ICU end-of-life patients in China. OBJECTIVE: The aim of this study was to revise and culturally adapt the Taiwanese version of the McGill Quality of Life Questionnaire (MQOL-Taiwan) and to test its reliability and validity to provide an effective instrument for assessing the quality of life of ICU patients at the end of life. METHODS: The revision and cultural adaptation of the MQOL-Taiwan were performed to develop a Chinese version of the McGill Quality of Life Questionnaire for ICU end-of-life patients (MQOL-ICU). A total of 156 ICU doctors, 286 ICU nurses and 120 ICU family members of end-of-life patients were surveyed with the revised scale to evaluate the quality of life of ICU patients at the end of life. The content validity, construct validity, and internal consistency of the scale were measured after the revision. RESULTS: The Chinese version of the MQOL-ICU scale was formed based on the MQOL-Taiwan scale, which includes 8 items. For the Chinese version of the MQOL-ICU, the item-content validity index (I-CVI) ranged from 0.789 to 0.905, and the average scale-level content validity index (S-CVI/Ave) was 0.845. After exploratory factor analysis, the Kaiser-Meyer-Olkin (KMO) value was 0.700, and 3 dominant factors were extracted: physical and psychological symptoms, existential well-being, and support. In addition, 70.385% of the total variance was explained. The internal consistency (Cronbach's α) coefficient of the whole MQOL-ICU was 0.804, and the coefficients for the 3 domains ranged from 0.779 to 0.833. CONCLUSION: The Chinese version of the MQOL-ICU showed good reliability and validity, and it can be used to assess the quality of life of ICU patients at the end of life.


Assuntos
Cuidados Paliativos , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , Cuidados Paliativos/psicologia , Inquéritos e Questionários , China , Morte , Unidades de Terapia Intensiva , Psicometria
2.
Oncol Lett ; 25(1): 4, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36419752

RESUMO

Hirsuteine is extracted from Uncaria rhynchophylla, the bark of which has traditionally been used to treat hypertension, cancer, convulsions, hemorrhage, auto-immune disorders, and other ailments. The anticancer properties of hirsuteine are of significant importance to the research community; however, its underlying mechanism of action is not well understood. The aim of the present study was to examine the antiproliferative ability of hirsuteine using human breast cancer MDA-MB-453 cells and to determine the underlying molecular mechanism involved in its therapeutic efficacy. The effects of hirsuteine on cell viability were determined using CCK-8 and colony formation assays, while apoptosis was assessed using flow cytometry. Cell cycle distribution was assessed using flow cytometry, and apoptotic cell quantification was performed using via Annexin V-FITC/PI staining and flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to assess the expression of cell cycle progression and apoptosis associated genes and proteins. MDA-MB-453 cell proliferation was significantly reduced by hirsuteine in a concentration and time-dependent manner. Hirsuteine-treated cells exhibited G2/M phase arrest, as evidenced by the increase in G2/M phase cells and a decrease in the G0/G1 phase cells, and this was related to cyclin B1 and CDK1 downregulation. Furthermore, hirsuteine accelerated MDA-MB-453 cell apoptosis by downregulating Bcl-2 while upregulating cytoplasmic cytochrome c, Bax, Apaf1, cleaved caspase-3, and cleaved caspase-9 levels, which together drove apoptotic cell death. Thus, hirsuteine suppressed MDA-MB-453 cancer cell proliferation by inducing cell cycle arrest and promoting apoptosis.

3.
Int Immunopharmacol ; 113(Pt A): 109263, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334370

RESUMO

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms. METHODS: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs). RESULTS: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes. CONCLUSION: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.

4.
RSC Adv ; 12(47): 30432-30435, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36337965

RESUMO

A novel Cu-catalyzed radical-radical cross coupling reaction of 3-aminoindazoles with sulfonyl hydrazides has been disclosed, enabling the production of diverse 1,3-substituted aminoindazoles in good yields. This methodology is distinguished by readily available starting materials, wide substrate scope and operational simplicity. In addition, a gram-scale reaction has been well demonstrated.

5.
Zhongguo Zhen Jiu ; 42(11): 1278-84, 2022 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-36397226

RESUMO

OBJECTIVE: To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. METHODS: Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. RESULTS: Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). CONCLUSION: Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.


Assuntos
Lesões Encefálicas , Prolil Hidroxilases , Animais , Ratos , Masculino , Prolil Hidroxilases/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos Sprague-Dawley , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Encéfalo/metabolismo , RNA Mensageiro , Água
6.
Clin Transl Med ; 12(11): e1113, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394206

RESUMO

BACKGROUND: Dysregulation of alternative splicing (AS) induced by serine/arginine-rich proteins has recently been linked to cancer metastasis. Nonetheless, as a member of the serine/arginine-rich protein family, the involvement of SRSF11 in colorectal cancer (CRC) is unknown. METHODS: The TCGA dataset and clinical samples were used to assess SRSF11 expression levels in CRC. For SRSF11, functional experiments were conducted both in vitro and in vivo. RNA-seq technology was used to analyze and screen SRSF11-triggered AS events, which were then confirmed by in vivo UV crosslinking and immunoprecipitation (CLIP) and mini-gene reporter assays. Jalview software was used to determine the preferential binding motif with relation to exon skipping (ES) events. Furthermore, coimmunoprecipitation (Co-IP) and Phospho-tag SDS-PAGE experiments were used to investigate PAK5-mediated phosphorylation regulation on SRSF11, and in vitro kinase experiments validated the interaction. RESULTS: In CRC, SRSF11 was discovered to be overexpressed and associated with a poor prognosis. And SRSF11 played a pro-metastatic role in vitro and in vivo. By screening SRSF11-regulated AS events, we identified the binding motif of SRSF11-triggered splicing-switching of HSPA12A AS, which specifically regulated HSPA12A AS by directly binding to a motif in exon 2. Mechanistically, the HSPA12A transcript with exon 2 retention increased N-cadherin expression by promoting RNA stability. Furthermore, the oncogenic kinase PAK5 phosphorylated SRSF11 at serine 287, protecting it from ubiquitination degradation. CONCLUSIONS: SRSF11 exerts pro-metastatic effects in CRC by inhibiting the AS of HSPA12A pre-RNA. Our findings point to SRSF11-regulated HSPA12A splicing as a novel relationship between SRSF11-regulated splicing and CRC metastasis and suggest a PAK5/SRSF11/HSPA12A axis as a potential therapeutic target and prognostic biomarker in CRC.


Assuntos
Processamento Alternativo , Neoplasias Colorretais , Humanos , Processamento Alternativo/genética , Arginina/genética , Arginina/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , RNA/metabolismo , Serina/genética , Serina/metabolismo
7.
Chin Med Sci J ; 37(3): 171-180, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36321172

RESUMO

Objective To explore the semi-supervised learning (SSL) algorithm for long-tail endoscopic image classification with limited annotations. Method We explored semi-supervised long-tail endoscopic image classification in HyperKvasir, the largest gastrointestinal public dataset with 23 diverse classes. Semi-supervised learning algorithm FixMatch was applied based on consistency regularization and pseudo-labeling. After splitting the training dataset and the test dataset at a ratio of 4:1, we sampled 20%, 50%, and 100% labeled training data to test the classification with limited annotations. Results The classification performance was evaluated by micro-average and macro-average evaluation metrics, with the Mathews correlation coefficient (MCC) as the overall evaluation. SSL algorithm improved the classification performance, with MCC increasing from 0.8761 to 0.8850, from 0.8983 to 0.8994, and from 0.9075 to 0.9095 with 20%, 50%, and 100% ratio of labeled training data, respectively. With a 20% ratio of labeled training data, SSL improved both the micro-average and macro-average classification performance; while for the ratio of 50% and 100%, SSL improved the micro-average performance but hurt macro-average performance. Through analyzing the confusion matrix and labeling bias in each class, we found that the pseudo-based SSL algorithm exacerbated the classifier's preference for the head class, resulting in improved performance in the head class and degenerated performance in the tail class. Conclusion SSL can improve the classification performance for semi-supervised long-tail endoscopic image classification, especially when the labeled data is extremely limited, which may benefit the building of assisted diagnosis systems for low-volume hospitals. However, the pseudo-labeling strategy may amplify the effect of class imbalance, which hurts the classification performance for the tail class.


Assuntos
Algoritmos , Aprendizado de Máquina Supervisionado
8.
Foods ; 11(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36360082

RESUMO

In this study, a potential producer of prebiotics, a novel endo-polygalacturonase pePGA from Penicillium rolfsii BM-6, was successfully expressed in Komagataella phaffii, characterized and applied to produce pectic oligosaccharides. The optimum temperature and pH of pePGA were 60 °C and 6.0. The purified recombinant enzyme showed a good pH stability and was stable from pH 3.5 to 8.0. The Km, Vmax and kcat values of pePGA were 0.1569 g/L, 12,273 µmol/min/mg and 7478.4 s-1, respectively. More importantly, pePGA-POS, the pePGA hydrolysis products from commercial pectin, had good prebiotic and antibacterial activities in vitro. The pePGA-POS was able to significantly promote the growth of probiotics; meanwhile, the growth of Escherichia coli JM109, Staphylococcus aureus and Bacillus subtilis 168 was effectively inhibited by pePGA-POS. In addition, pePGA-POS also had the DPPH radical scavenging capacity. These properties of pePGA-POS make pePGA attractive for the production of prebiotics.

9.
Br J Radiol ; : 20220404, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400064

RESUMO

OBJECTIVE: To assess the added value of contrast-enhanced ultrasound (CEUS) to conventional ultrasound (US) in differentiating benign soft-tissue tumors from malignant ones. METHODS: One hundred and night-seven soft-tissue tumors underwent US examination with confirmed histopathology were retrospectively evaluated. The radiologists classified all the tumors as benign, malignant, or indeterminate according to US features. The indeterminate tumors underwent CEUS were reviewed afterwards for malignancy identification by using individual and combined CEUS features. RESULTS: US analysis classified 62 soft-tissue tumors as benign, 111 tumors as indeterminate and 24 tumors as malignant. There were 104 indeterminate tumors that underwent CEUS. Three CEUS features of enlargement of enhancement area, infiltrative enhancement boundary, and intratumoral arrival time difference were significantly associated with the tumor nature in both univariable and multivariable analysis in the indeterminate tumors (all p < 0.05). When at least one out of the three discriminant CEUS features were present, the best sensitivity of 100% for malignancy identification was obtained with the specificity of 66.7% and the AUC of 0.833. When at least two of the three discriminant CEUS features were present, the best area under the receiver operating characteristic curve (AUC) of 0.924 for malignancy identification was obtained. The combination of at least two discriminant CEUS features showed much better diagnostic performance than the optimal combination of US features in terms of AUC (0.924 vs 0.608, p < 0.0001), sensitivity (94.0% vs 42.0%, p < 0.0001), and specificity (90.7% vs 79.6%, p = 0.210) in the indeterminate tumors. CONCLUSION: The combination CEUS features of enlargement of enhancement area, infiltrative enhancement boundary and intratumoral arrival time difference are valuable to improve the discriminating performance in indeterminate soft-tissue tumors on conventional US. ADVANCES IN KNOWLEDGE: The combination of peritumoral and arrival-time CEUS features can improve the discriminating performance in indeterminate soft-tissue tumors on conventional US.

10.
Animals (Basel) ; 12(22)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36428445

RESUMO

The present study investigated the effects of dietary riboflavin on growth performance, body composition and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts. Seven experimental diets were formulated with graded riboflavin levels of 0.00, 3.96, 8.07, 16.11, 31.81, 63.67 and 126.69 mg/kg, respectively. Each diet was fed to triplicate groups of 10 fish with an individually initial mean body weight of 186.22 ± 0.41 g in 21 cages (water volume, 1000-L/cage) and fed three times daily (7:30, 12:30 and 17:30) to apparent satiation for 12 weeks. Fish fed a diet with 31.81 mg/kg riboflavin had the highest specific growth rate (SGR), which was significantly higher than fish-fed diets with 0.00, 3.96, 8.07 and 126.69 mg/kg riboflavin (p < 0.05). Feed conversion ratio showed an inverse trend with SGR. No significant differences were observed in condition factor, hepatosomatic index, viscerosomatic index, muscle moisture, crude protein and ash contents among dietary groups. Muscle lipid had the highest content in the 31.81 mg/kg group and was significantly higher (p < 0.05) than those in the 0.00, 3.96 and 8.07 mg/kg groups. The alanine aminotransferase, aspartate aminotransferase and malondialdehyde contents in the liver and serum of fish were significantly decreased with the increase in dietary riboflavin level up to 31.81 mg/kg, and then increased as dietary riboflavin level further increased. An inverse trend was observed for total superoxide dismutase and catalase activities. Serum total cholesterol and triglyceride levels were significantly decreased with the dietary of riboflavin levels up to 31.81 and 63.67 mg/kg, respectively. The cubic curve regression analysis based on SGR indicated that the optimum dietary riboflavin level was estimated to be 35.26 mg/kg for coho salmon post-smolts.

11.
ACS Synth Biol ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416371

RESUMO

As a natural biological macromolecule, γ-polyglutamic acid (γ-PGA) plays a significant role in medicine, food, and cosmetic industries owing to its unique properties of biocompatibility, biodegradability, water solubility, and viscosity. Although many strategies have been adopted to increase the yield of γ-PGA in Bacillus subtilis, the effectiveness of these common approaches is not high because the strong viscosity affects cell growth. However, dynamic regulation based on quorum sensing (QS) has been extensively applied as a fundamental tool for fine-tuning gene expression in reaction to changes in cell density without adding expensive inducers. A modular PhrQ-RapQ-DegU QS system is developed based on promoter PD4, which is upregulated by phosphorylated DegU (DegU-P). In this study, first, we analyzed the DegU-based gene expression regulation system in B. subtilis 168. We constructed a promoter library of different abilities, selected suitable promoters from the library, and performed mutation screening on the selected promoters and degU region. Furthermore, we constructed a PhrQ-RapQ-DegU QS system to dynamically control the synthesis of γ-PGA in BS168. Cell growth and efficient synthesis of the target product can be dynamically balanced by the QS system. Our dynamic adjustment approach increased the yield of γ-PGA to 6.53-fold of that by static regulation in a 3 L bioreactor, which verified the effectiveness of this strategy. In summary, the PhrQ-RapQ-DegU QS system has been successfully integrated with biocatalytic functions to achieve dynamic metabolic pathway control in BS168, which can be stretched to a large number of microorganisms to fine-tune gene expression and enhance the production of metabolites.

12.
Int J Nanomedicine ; 17: 5339-5351, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36415817

RESUMO

Purpose: Pt-based nanostructures are one of the promising nanomaterials for being used in catalysts, sensors, and therapeutics. However, their impacts on the health and biological systems are not adequately understood yet. Methods: In this work, nanorods composed of ultrasmall platinum (Pt) nanoparticles deposited on the surface and gold nanorod as the core (Au@Pt NRs) were synthesized, and the distribution and toxic effects of Au@Pt NRs were investigated in C57BL/6 mice with intravenous injection by using atomic absorption spectroscopy (AAS), transmission electron microscope (TEM), hematoxylin-eosin (HE) staining and blood cell analyzer. Results: At the time point of Day 1, Day 8 and Day 16 post injection of Au@Pt NRs (6 mg/kg of Pt atom), Au@Pt NRs were mainly accumulated in the liver and spleen. The energy dispersive spectrometer mapping images showed Au@Pt NRs experienced quick corrosion and Au released faster than Pt in the physiological environments. The catalase (CAT) activity in tissues increased slightly in the early stage of the Au@Pt NRs exposure and went down to the normal level. With HE staining, inflammatory cells infiltration could be seen in the tissues, while no significant influences were detected on the blood biochemistry and the function of liver and kidney. Conclusion: In conclusion, intravenously injected Au@Pt NRs mainly distributed in the liver and spleen with comparable levels, and did not exert any significant toxic effects on the organs' function within two weeks; meanwhile, Au@Pt NRs were able to degrade, which indicated acceptable safety to the mice and potentials of biomedical application.


Assuntos
Nanopartículas , Nanotubos , Camundongos , Animais , Platina/toxicidade , Platina/química , Distribuição Tecidual , Injeções Intravenosas , Camundongos Endogâmicos C57BL , Nanotubos/toxicidade , Nanotubos/química
13.
Bioresour Technol ; : 128362, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36423771

RESUMO

An NH4+-NO2--rich wastewater discharged from a composting-biotrickling filter coupled system can be reused as a composting moisture adjustment agent. To investigate the impact mechanism of reuse, NH4+-NO2--rich wastewater, NH4+-rich wastewater, NO2--rich wastewater, and distilled water were added into the composting (i.e., AMN, AAN, ANO2, and ADW groups). Results show that compost of all groups met the corresponding criteria for stabilization, humification, and non-phytotoxicity of mature compost. AMN increased organic-N and NO3--N content and reduced NH3 emissions, like AAN or ANO2, and avoid stimulating N2O emission in AAN and ANO2. Furthermore, LEfSe analysis of microorganisms revealed that AMN reduced NH3 emissions and increase organic-N content probably due to the inhibition of Alphaproteobacteria by ammonium, and increased nitrate content probably due to the stimulation of Aquamicrobium by nitrite. The avoided N2O emission is probably due to a negative synergistic effect on the stimulation from ammonia and nitrite to denitrifying bacteria (eg., Sphingobacteriaceae).

14.
Front Psychiatry ; 13: 997758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213924

RESUMO

Objective: This study aimed to investigate white matter (WM) microstructural alterations and their relationship correlation with disease severity in anti-NMDA receptor (NMDAR) encephalitis. Multivariate pattern analysis (MVPA) was applied to discriminate between patients and healthy controls and explore potential imaging biomarkers. Methods: Thirty-two patients with anti-NMDAR encephalitis and 26 matched healthy controls underwent diffusion tensor imaging. Tract-based spatial statistics and atlas-based analysis were used to determine WM microstructural alterations between the two groups. MVPA, based on a machine-learning algorithm, was applied to classify patients and healthy controls. Results: Patients exhibited significantly reduced fractional anisotropy in the corpus callosum, fornix, cingulum, anterior limb of the internal capsule, and corona radiata. Moreover, mean diffusivity was increased in the anterior corona radiata and body of the corpus callosum. On the other hand, radial diffusivity was increased in the anterior limb of the internal capsule, cingulum, corpus callosum, corona radiata, and fornix. WM changes in the cingulum, fornix, and retrolenticular part of the internal capsule were correlated with disease severity. The accuracy, sensitivity, and specificity of fractional anisotropy-based classification were each 78.33%, while they were 67.71, 65.83, and 70% for radial diffusivity. Conclusion: Widespread WM lesions were detected in anti-NMDAR encephalitis. The correlation between WM abnormalities and disease severity suggests that these alterations may serve a key role in the pathophysiological mechanisms of anti-NMDAR encephalitis. The combination of tract-based spatial statistics and MVPA may provide more specific and complementary information at the group and individual levels.

15.
Pharmacol Res ; 185: 106503, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36241000

RESUMO

Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a high rate of relapse and a very low 5-year survival percentage of less than 25%. CXCR4 is a highly expressed chemokine receptor in multiple types of AML cells and closely associated with the drug resistance and relapse. In this work, we integrate a chemically synthesized CXCR4 antagonistic peptide and doxorubicin using DSPE-mPEG2000 micelles (referred to as M-E5-Dox) that is applied to a very challenging refractory AML mouse model as well as human AML cell lines. Results showed that M-E5-Dox can effectively bind to the CXCR4-expressing AML cells, downregulating the signaling proteins mediated by CXCR4/CXCL12 axis and increasing the cellular uptake of Dox. Importantly, M-E5-Dox remarkably decreases the leukemic cells in the peripheral blood and bone marrow, as well as their infiltration in the spleen and liver of the AML mice, which in turn prolongs the survival significantly. Meanwhile, M-E5-Dox did not increase the cardiotoxicity of Dox. In conclusion, M-E5-Dox harnesses the functions of CXCR4 specific binding and CXCR4 antagonism of the peptide and the tumor cell killing capacity of Dox, which displays significant therapeutic effects and promising translational potentials for the treatment of refractory AML.


Assuntos
Leucemia Mieloide Aguda , Humanos , Camundongos , Animais , Leucemia Mieloide Aguda/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Transdução de Sinais , Peptídeos/farmacologia , Recidiva , Receptores CXCR4
16.
Medicine (Baltimore) ; 101(42): e30981, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281181

RESUMO

Psychological disorders often occur among parents of children with cancer. The current study aimed to explore the longitudinal change of anxiety and depression and their related factors among parents of childhood and adolescence patients with osteosarcoma. A total of 56 childhood and adolescence patients with osteosarcoma who underwent tumor resection and corresponding 104 parents were enrolled. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and HADS-Depression (HADS-D) of parents were evaluated at baseline (the day of patients' hospital discharge), 0.5 year, 1 year, 2 years, and 3 years. From baseline to the 3rd year, HADS-A (from 8.3 ±â€…3.1 to 9.4 ±â€…3.1. P < .001), HADS-D score (from 7.7 ±â€…3.2 to 8.8 ±â€…2.9, P = .001), anxiety rate (from 45.2% to 60.6%, P = .038), depression rate (from 38.5% to 57.7%, P = .002) were elevated; meanwhile, anxiety severity (P = .001) and depression severity (P = .001) were also increased. Furthermore, multivariate logistic regression analysis presented that the role of mother, divorced/widowed marital status, declined family annual income, elevated Enneking stage, and amputation were independently correlated with elevated risk of parents' baseline anxiety or depression (all P < .05). Additionally, declined family annual income, elevated Enneking stage, and amputation were independently correlated with increased risk of parents' 3-year anxiety or depression (all P < .05). Anxiety and depression deteriorate with time in parents of childhood and adolescence patients with osteosarcoma, which are affected by parental role, marital status, family annual income, surgery type, and Enneking stage.


Assuntos
Depressão , Osteossarcoma , Criança , Feminino , Humanos , Adolescente , Depressão/etiologia , Estudos de Coortes , Ansiedade/etiologia , Pais/psicologia , Fatores de Risco , Osteossarcoma/epidemiologia , Osteossarcoma/cirurgia
17.
Front Microbiol ; 13: 932294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312920

RESUMO

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.

18.
Respir Physiol Neurobiol ; 308: 103980, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36273780

RESUMO

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by intermittent and recurrent upper airway collapse during sleep that leads to chronic intermittent hypoxia (CIH). The genioglossus (GG) is the largest dilator muscle, which controls the upper airway and plays an important role in OSA pathology. Elucidating its genetic alterations may help identify potential targets for OSA. However, the genetic aspects of the GG in CIH mice remain unclear. Here, we have conducted an RNA sequencing (RNA-Seq) analysis to assess the differentially expressed genes (DEGs) in the GG between CIH mice and normoxia (NOR) mice. A total of 637 DEGs were identified to be dysregulated in CIH mice compared with control mice. Bioinformatics analysis showed that the DEGs were related to various physiological processes, such as the endogenous stimulus responses, cellular component organization and metabolic processes. Extracellular matrix (ECM)-receptor interaction was the top KEGG pathway in the environmental information processing category with high significance and large fold changes. From the gene weight distributions of collagen (Col)-related biological processes (BPs), we found several significant DEGs, such as Col1a1, Col1a2, Mmp2, Col3a1, Col5a1, Fmod, and Col5a2. A PPI network showed that Col1a1 was linked to ECM-receptor interactions, responses to reactive oxygen species (ROS) and Col-related BPs. It was verified in vivo and in vitro that hypoxia can induce excess ROS and reduce Col expression levels. Moreover, we found NAC can effectively scavenge ROS and restore collagen synthesis. These findings contribute to a better understanding of the mechanisms linking OSA and upper airway muscle injury and may help identify potential therapeutic targets.

19.
Mater Today Bio ; 16: 100415, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36105673

RESUMO

Myocardium is an excitable tissue with electrical conductivity and mechanical strength. In this work, carbon fibers (CFs) and co-axial fibrous mesh were integrated which combined the high modulus and excellent electrical conductivity of CFs and the fibrous and porous structures of the electrospun fibers. The scaffold was fabricated by simply integrating coaxial electrospun fibers and carbon fibers through a freeze-drying procedure. It was shown that the integration of carbon fibers have the conductivity and Young's modulus of the fibrous mesh increased significantly, meanwhile, upregulated the expression of CX43, α-actinin, RhoA of the neonatal rat primary cardiomyocytes and primary human umbilical vein endothelial cells (HUVECs), and promoted the secretion of VEGF of HUVECs. Moreover, the cardiomyocytes grown on the scaffolds increased the ability of HUVECs migration. When implanted to the injury area post myocardial infraction, the scaffolds were able to effectively enhance the tissue regeneration and new vessel formation, which rescued the heart dysfunction induced by the myocardial infraction, evidenced by the results of echocardiography and histochemical analysis. In conclusion, the composite scaffolds could promote the myocardium regeneration and function's recovery by enhancing cardiomyocytes maturation and angiogenesis and establishing the crosstalk between the cardiomyocytes and the vascular endothelial cells.

20.
Clin Nutr ; 41(10): 2333-2344, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36113229

RESUMO

The mammalian gastrointestinal tract is colonized with a majority of gut microbes, affecting host metabolism and homeostasis. Gut microbiota plays a vital role in nutrient exchange, signaling transduction between intestinal epithelial cells, and resistance to pathogen invasion. Gut microbiota is divided into mucus layer bacteria and intestinal lumen bacteria based on the colonization distribution. Akkermansia muciniphila (A. muciniphila) prefers to colonize in the intestinal mucus layer, and specifically degrades mucins to produce short-chain fatty acids, providing energy for the host and promoting colonization of the bacterium itself. Degradation of mucins prompts the host to compensate for the production of more mucins, thereby maintaining the dynamics of these proteins. In the intestinal micro-ecosystem, A. muciniphila is non-pathogenic, and its colonization with suitable abundance contributes to the development of immune system, thus promoting intestinal health. The mechanisms by which A. muciniphila bears a protective role in the host intestine are currently unclear. In this review, we summarize the microenvironment for the colonization of A. muciniphila, physiological characteristics and pathophysiological impact of A. muciniphila on intestinal diseases, such as irritable bowel syndrome, inflammatory bowel diseases, and intestinal tumors. We also provided updates for current studies on signals that A. muciniphila enhances intestinal barrier integrity and regulates immune response. Together, we conclude that A. muciniphila is a promising probiotic, which could be a microbial target for the treatment of multiple intestinal diseases.


Assuntos
Ecossistema , Doenças Inflamatórias Intestinais , Akkermansia , Animais , Ácidos Graxos Voláteis/metabolismo , Humanos , Mamíferos , Mucinas/metabolismo , Verrucomicrobia/metabolismo
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