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1.
Exp Eye Res ; 238: 109751, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38097101

RESUMEN

Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1ß, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.


Asunto(s)
Neovascularización Coroidal , Células Endoteliales , Ratones , Animales , Humanos , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Sincalida/metabolismo , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/prevención & control , Neovascularización Coroidal/metabolismo , Hipoxia/metabolismo , Modelos Animales de Enfermedad , Epitelio Pigmentado de la Retina/metabolismo
2.
BMC Geriatr ; 24(1): 502, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844849

RESUMEN

BACKGROUND: Sedentary behavior (SB) is deeply ingrained in the daily lives of community-dwelling older adults with type 2 diabetes mellitus (T2DM). However, the specific underlying mechanisms of the determinants associated with SB remain elusive. We aimed to explore the determinants of SB based on the behavior change wheel framework as well as a literature review. METHODS: This cross-sectional study recruited 489 community-dwelling older adults with T2DM in Jinan City, Shandong Province, China. Convenience sampling was used to select participants from relevant communities. This study used the Measure of Older Adults' Sedentary Time-T2DM, the Abbreviated-Neighborhood Environment Walkability Scale, the Social Support Rating Scale, the Lubben Social Network Scale 6, the Subjective Social Norms Questionnaire for Sedentary Behavior, the Functional Activities Questionnaire, the Numerical Rating Scale, the Short Physical Performance Battery, and the Montreal Cognitive Assessment Text to assess the levels of and the determinants of SB. Descriptive statistical analysis and path analysis were conducted to analyze and interpret the data. RESULTS: Pain, cognitive function, social isolation, and social support had direct and indirect effects on SB in community-dwelling older adults with T2DM (total effects: ß = 0.426, ß = -0.171, ß = -0.209, and ß = -0.128, respectively), and physical function, walking environment, and social function had direct effects on patients' SB (total effects: ß = -0.180, ß = -0.163, and ß = 0.127, respectively). All the above pathways were statistically significant (P < 0.05). The path analysis showed that the model had acceptable fit indices: RMSEA = 0.014, χ 2/df = 1.100, GFI = 0.999, AGFI = 0.980, NFI = 0.997, RFI = 0.954, IFI = 1.000, TLI = 0.996, CFI = 1.000. CONCLUSION: Capability (physical function, pain, and cognitive function), opportunity (social isolation, walking environment, and social support), and motivation (social function) were effective predictors of SB in community-dwelling older adults with T2DM. Deeper knowledge regarding these associations may help healthcare providers design targeted intervention strategies to decrease levels of SB in this specific population.


Asunto(s)
Diabetes Mellitus Tipo 2 , Vida Independiente , Conducta Sedentaria , Humanos , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/epidemiología , Anciano , Masculino , Femenino , Estudios Transversales , Vida Independiente/psicología , Apoyo Social , China/epidemiología , Persona de Mediana Edad , Aislamiento Social/psicología , Encuestas y Cuestionarios , Anciano de 80 o más Años
3.
Anal Chem ; 95(38): 14228-14234, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37699407

RESUMEN

Fluorescence spectrometer (FS) is widely used for component analysis because each fluorescing material has its own characteristic spectrum. However, the spectral calibration is complicated and bulky. Herein, an in-line spectral calibration sheet (ISCS) was proposed in which a narrow band-pass filter and a linear variable filter (LVF) were integrated on a metal plate. By moving the ISCS, the transmitted excitation light power (TEP) as well as fluorescence spectrum can be seamlessly scanned, and the TEP can be used for in-line spectral calibration. A compact FS apparatus based on UV-LED excitation, metal capillary (MC) and ISCS was fabricated (i.e., ISCS-FS), and the ISCS-FS apparatus was applied to detect sodium humate in water. By employing TEP calibration, both the primary inner filter effect (PIFE) and the drift in the optical power of UV-LED can be simultaneously compensated. The linear correlation coefficient of signal concentration was improved from 0.89 to 0.998, and the relative standard deviation (RSD) of replicated detection was improved from 3 to 0.7%. A detection limit of concentration (DLC) of 1.3 µg/L was realized, which is 15-fold lower than that of a commercial FS apparatus (20 µg/L). The DLC is even comparable with that (0.5-4 µg/L) of commercial total organic carbon (TOC) analyzers, which are bulky and expensive. The linear correlation between the measurement results of ISCS-FS and commercial TOC analyzers can reach a good value of 0.94.

4.
Opt Express ; 31(5): 7983-7993, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36859917

RESUMEN

In order to increase the optical path and related sensitivity of photometers, multiple axial-reflection of parallel light-beam inside a capillary cavity is one of the most effective ways. However, there is a non-optimum trade-off between optical path and light intensity, e.g., smaller aperture on cavity mirror can increase multiple axial-reflection times (i.e., longer optical path) due to the lower cavity-loss, but it would also reduce coupling efficiency, light intensity, and related signal-to-noise ratio. Herein, an optical beam shaper, which is composed of two optical lenses with an apertured mirror, was proposed to focus the light beam (i.e., increasing coupling efficiency) without deteriorating beam parallelism and related multiple axial-reflection. Thus, by combining the optical beam shaper with a capillary cavity, large optical path enhancement (10-fold of capillary length) and high coupling efficiency (>65%) can be realized simultaneously, where the coupling efficiency was improved 50-fold. An optical beam shaper photometer (with a 7 cm long capillary) was fabricated and applied to detect water in ethanol with a detection limit of 12.5 ppm, which is 800-fold and 32∼80 fold lower than that of the commercial spectrometer (1 cm cuvette) and previous reports, respectively.

5.
J Magn Reson Imaging ; 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37800893

RESUMEN

BACKGROUND: Injury to the spinal cord of children may cause potential brain reorganizations, affecting their rehabilitation. However, the specific functional alterations of children after complete spinal cord injury (CSCI) remain unclear. PURPOSE: To explore the specific functional changes in local brain and the relationship with clinical characteristics in pediatric CSCI patients, clarifying the impact of CSCI on brain function in developing children. STUDY TYPE: Prospective. SUBJECTS: Thirty pediatric CSCI patients (7.83 ± 1.206 years) and 30 age-, gender-matched healthy children as controls (HCs) (8.77 ± 2.079 years). FIELD STRENGTH/SEQUENCE: 3.0 T/Resting-state functional MRI (rs-fMRI) using echo-planar-imaging (EPI) sequence. ASSESSMENT: Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were used to characterize regional neural function. STATISTICAL TESTS: Two-sample t-tests were used to compare the ALFF, fALFF, ReHo values of the brain between pediatric CSCI and HCs (voxel-level FWE correction, P < 0.05). Spearman correlation analyses were performed to analyze the associations between the ALFF, fALFF, ReHo values in altered regions and the injury duration, sensory motor scores of pediatric CSCI patients (P < 0.05). Then receiver operating characteristic (ROC) analysis was conducted to identify possible sensitive imaging indicators for clinical therapy. RESULTS: Compared with HCs, pediatric CSCI showed significantly decreased ALFF in the right postcentral gyrus (S1), orbitofrontal cortex, and left superior temporal gyrus (STG), increased ALFF in bilateral caudate nucleus, thalamus, middle cingulate gyrus, and cerebellar lobules IV-VI, and increased ReHo in left cerebellum Crus II and Brodmann area 21. The ALFF value in the right S1 negatively correlated with the pinprick and light touch sensory scores of pediatric CSCI. When the left STG was used as an imaging biomarker for pediatric CSCI, it achieved the highest area under the curve of 0.989. CONCLUSIONS: These findings may provide potential neural mechanisms for sensory motor and cognitive-emotional deficits in children after CSCI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

6.
Curr Genomics ; 24(2): 110-127, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37994323

RESUMEN

Background: Due to the heterogeneity of Hepatocellular carcinoma (HCC), there is an urgent need for reliable diagnosis and prognosis. Mitochondria-mediated abnormal lipid metabolism affects the occurrence and progression of HCC. Objective: This study aims to investigate the potential of mitochondrial lipid metabolism (MTLM) genes as diagnostic and independent prognostic biomarkers for HCC. Methods: MTLM genes were screened from the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) databases, followed by an evaluation of their diagnostic values in both The Cancer Genome Atlas Program (TCGA) and the Affiliated Cancer Hospital of Guangxi Medical University (GXMU) cohort. The TCGA dataset was utilized to construct a gene signature and investigate the prognostic significance, immune infiltration, and copy number alterations. The validity of the prognostic signature was confirmed through GEO, International Cancer Genome Consortium (ICGC), and GXMU cohorts. Results: The diagnostic receiver operating characteristic (ROC) curve revealed that eight MTLM genes have excellent diagnostic of HCC. A prognostic signature comprising 5 MTLM genes with robust predictive value was constructed using the lasso regression algorithm based on TCGA data. The results of the Stepwise regression model showed that the combination of signature and routine clinical parameters had a higher area under the curve (AUC) compared to a single risk score. Further, a nomogram was constructed to predict the survival probability of HCC, and the calibration curves demonstrated a perfect predictive ability. Finally, the risk score also unveiled the different immune and mutation statuses between the two different risk groups. Conclusion: MTLT-related genes may serve as diagnostic and prognostic biomarkers for HCC as well as novel therapeutic targets, which may be beneficial for facilitating further understanding the molecular pathogenesis and providing potential therapeutic strategies for HCC.

7.
Artículo en Inglés | MEDLINE | ID: mdl-37944976

RESUMEN

Objective: To explore the clinical study of glutamine combined with early enteral nutrition support on the nutritional status of gastric cancer patients undergoing neoadjuvant chemotherapy. Methods: Divided into control and observation groups, a control group received routine enteral nutrition, while the observation group received an additional 0.5 g/kg/d of glutamine. The researchers measured nutritional indicators, immunoglobulins, T lymphocyte subsets, and stress indexes such as fasting blood sugar and C-reactive protein throughout the study. Results: Before nutritional support, there was no significant difference in the HGB, TP, and ALB levels. During nutritional support, however, the observation group began registering significantly higher levels of HGB, TP, and ALB, suggesting that glutamine intervention can improve the nutritional status of patients. Throughout the study, the CD4+ level showed a consistent increase in the observation group. The levels of IgA and IgG in the observation group also grew significantly higher. Both groups had higher blood glucose levels before nutritional support. However, on day 8 and day 15, the levels decreased. The observation group had significantly lower fasting blood glucose (FBG) levels than the control group. By day 15, the FBG levels in the observation group were close to normal. The CRP level showed a consistent decrease in the observation group compared to the control group on day 8 and day 15. Glutamine intervention appears to improve the stress capacity of gastric cancer patients undergoing neoadjuvant chemotherapy. Overall, the findings suggest that glutamine intervention in enteral nutrition can significantly improve immune function, nutritional status, and stress capacity in gastric cancer patients undergoing neoadjuvant chemotherapy and appears to be more effective than conventional enteral nutrition. Conclusion: The combination of glutamine and early enteral nutrition support can significantly improve gastric cancer patients undergoing neoadjuvant chemotherapy's nutritional status and immune function levels. It is a safe and reliable enteral nutrition support method worthy of clinical promotion.

8.
Clin Oral Investig ; 27(5): 1953-1964, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36637519

RESUMEN

OBJECTIVES: To assess the clinical efficacy of xenogeneic collagen matrix (XCM) plus apically positioned flap (APF) in augmenting the keratinized mucosa (KM) width (KMW) and thickness (KMT) around posterior mandibular implants and compare it with free gingival graft (FGG) plus APF. MATERIAL AND METHODS: Thirty patients with KMW ≤ 2 mm in the posterior mandibular implant site were randomly allocated to the FGG group (FGG plus APF) or the XCM group (XCM plus APF). Clinical assessments, including KMW and KMT, shrinkage rate of established KM, and peri-implant soft tissue health, were evaluated during a 6-month follow-up. Additionally, the esthetic outcomes and patient-reported postoperative morbidity were investigated. RESULTS: At 6 months, the KMW measured 3.60 ± 0.79 mm in the FGG group and 3.28 ± 0.96 mm in the XCM group (p = 0.186). Both groups showed a tendency for graft contraction (FGG, 42.11%; XCM, 53.22%). The KMT measured 1.24 ± 0.34 mm in the FGG group and 0.95 ± 0.29 mm in the XCM group, with statistical difference (p = 0.002). No difference in the peri-implant soft tissue health was observed between the two groups (p > 0.05), but the esthetic outcomes were better in the XCM group (p < 0.05). CONCLUSIONS: XCM plus APF rendered a similar clinical efficacy in augmenting KMW as that with FGG plus APF, but with higher shrinkage. XCM plus APF was inferior with respect to FGG plus APF in augmenting KMT. The esthetic outcomes were better with XCM plus APF than FGG plus APF. Clinical relevance XCM plus APF graft was inferior with respect to FGG plus APF in augmenting KMT. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058027 and date: 03/27/2022.


Asunto(s)
Implantes Dentales , Gingivoplastia , Humanos , Gingivoplastia/métodos , Tejido Conectivo/trasplante , Estética Dental , Colágeno/uso terapéutico , Membrana Mucosa , Encía/trasplante
9.
Hepatology ; 73(5): 1797-1815, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33058300

RESUMEN

BACKGROUND AND AIMS: Trimethylation of Lys36 on histone 3 (H3K36me3) catalyzed by histone methyltransferase SET domain-containing 2 (SETD2) is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. APPROACH AND RESULTS: Here, using a liver-specific Setd2 depletion model, we found that Setd2 deficiency is sufficient to trigger spontaneous HCC. Meanwhile, Setd2 depletion significantly increased tumor and tumor size of a diethylnitrosamine-induced HCC model. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also by regulating lipid metabolism in the liver. Setd2 deficiency down-regulated H3K36me3 enrichment and expression of cholesterol efflux genes and caused lipid accumulation. High-fat diet enhanced lipid accumulation and promoted the development of HCC in Setd2-deficient mice. Chromatin immunoprecipitation sequencing analysis further revealed that Setd2 depletion induced c-Jun/activator protein 1 (AP-1) activation in the liver, which was trigged by accumulated lipid. c-Jun acts as an oncogene in HCC and functions through inhibiting p53 in Setd2-deficient cells. CONCLUSIONS: We revealed the roles of Setd2 in HCC and the underlying mechanisms in regulating cholesterol homeostasis and c-Jun/AP-1 signaling.


Asunto(s)
Carcinoma Hepatocelular/etiología , N-Metiltransferasa de Histona-Lisina/deficiencia , Metabolismo de los Lípidos , Neoplasias Hepáticas/etiología , Hígado/metabolismo , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Colesterol/sangre , Inmunoprecipitación de Cromatina , Edición Génica , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Células Hep G2 , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Triglicéridos/sangre
10.
Arch Microbiol ; 204(7): 446, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35778621

RESUMEN

Scalp pruritus is a common skin problem that remains therapeutic challenge. The relationships between the dysbiosis of microbiota and skin diseases have caught attention recently. However, there are few reports about microbiota on itchy scalp. This study investigated scalp microbial characteristics of subjects with mild scalp pruritus of undetermined origin and preliminarily screened physiological factors and bacteria potentially related to pruritus. The pruritus severity of 17 qualified females was evaluated by Visual Analogue Scale (VAS). Microbiota collection was done at both itchy (n = 20) and non-itchy sites (n = 27) at occiput and crown of the same subject and Illumina sequencing was performed at the V3-V4 hypervariable regions of 16S rRNA. The corresponding sebum content, hydration, pH, trans-epidermal water loss, erythema index and porphyrin numbers were also measured by skin tester. We identified 3044 amplicon sequence variants from 821 genera. The itchy and non-itchy sites had different microbiota structures (p = 0.045, by multivariate analysis of variance), while there were large inter- and intra-individual variations. Both sites had Staphylococcus, Cutibacterium and Lawsonella as predominant genera, which were not significantly related to pruritus. The use of three genera Lactobacillus, Morganella and Pseudomonas, could well distinguish non-itchy from itchy groups, whereas different composition patterns existed inside each group. Our investigation indicated that though the bacterial community structure on itchy scalp was individual specific, there was difference between itchy and non-itchy sites. The study provides new insights into microbiota profiling on itchy scalp, which will help microbiota-targeted therapeutic experiment or products design for scalp pruritus.


Asunto(s)
Microbiota , Cuero Cabelludo , Femenino , Humanos , Microbiota/genética , Prurito , ARN Ribosómico 16S/genética , Piel/microbiología
11.
Inorg Chem ; 61(35): 13883-13892, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-35998569

RESUMEN

Radioactive iodine (129I and 131I), produced or released from nuclear-related activities, posed severe effects on both human health and environment. The efficient removal of radioiodine from aqueous medium and vapor phase is of paramount importance for the sustainable development of nuclear energy. Herein, a metal-organic framework (MOF) nanosheet with a positive charge was constructed for the capture of iodine for the first time. The as-synthesized ultrathin nanosheets, with a thickness of 4.4 ± 0.1 nm, showed a record-high iodine adsorption capacity (3704.08 mg g-1) from aqueous solution, which is even higher than that from the vapor phase (3510.05 mg g-1). It can be ascribed to the fully interactions between the extensive accessible active sites on the largely exposed surface of 2D MOF nanosheets and the target pollutants, which also gave rise to fast adsorption kinetics with relative high removal efficiencies in the low concentrations, even in seawater. Moreover, a facile recyclability with fast desorption kinetics can also be achieved for the MOF nanosheets. The excellent iodine removal performance in aqueous solution demonstrated that the electrostatic attraction between MOF nanosheets with a positive charge and the negatively charged triiodide (I3-, the dominant form of iodine in aqueous solution) is the driving force in adsorption, which endows the adsorbents with the characteristics of fast adsorption and desorption kinetics. The adsorption mechanism was systematically verified by the studies of ζ potential, Fourier transform infrared, X-ray photoelectron spectroscopy, and Raman spectra.


Asunto(s)
Yodo , Estructuras Metalorgánicas , Neoplasias de la Tiroides , Contaminantes Químicos del Agua , Adsorción , Humanos , Yoduros , Radioisótopos de Yodo , Estructuras Metalorgánicas/química , Agua , Contaminantes Químicos del Agua/análisis
12.
Appl Microbiol Biotechnol ; 106(21): 7099-7112, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36184690

RESUMEN

Komagataeibacter xylinus is an aerobic strain that produces bacterial cellulose (BC). Oxygen levels play a critical role in regulating BC synthesis in K. xylinus, and an increase in oxygen tension generally means a decrease in BC production. Fumarate nitrate reduction protein (FNR) and aerobic respiration control protein A (ArcA) are hypoxia-inducible factors, which can signal whether oxygen is present in the environment. In this study, FNR and ArcA were used to enhance the efficiency of oxygen signaling in K. xylinus, and globally regulate the transcription of the genome to cope with hypoxic conditions, with the goal of improving growth and BC production. FNR and ArcA were individually overexpressed in K. xylinus, and the engineered strains were cultivated under different oxygen tensions to explore how their overexpression affects cellular metabolism and regulation. Although FNR overexpression did not improve BC production, ArcA overexpression increased BC production by 24.0% and 37.5% as compared to the control under oxygen tensions of 15% and 40%, respectively. Transcriptome analysis showed that FNR and ArcA overexpression changed the way K. xylinus coped with oxygen tension changes, and that both FNR and ArcA overexpression enhanced the BC synthesis pathway. The results of this study provide a new perspective on the effect of oxygen signaling on growth and BC production in K. xylinus and suggest a promising strategy for enhancing BC production through metabolic engineering. KEY POINTS: • K. xylinus BC production increased after overexpression of ArcA • The young's modulus is enhanced by the ArcA overexpression • ArcA and FNR overexpression changed how cells coped with changes in oxygen tension.


Asunto(s)
Celulosa , Gluconacetobacter xylinus , Humanos , Celulosa/metabolismo , Nitratos/metabolismo , Gluconacetobacter xylinus/genética , Gluconacetobacter xylinus/metabolismo , Oxígeno/metabolismo , Fumaratos/metabolismo , Hipoxia
13.
Drug Metab Dispos ; 49(5): 369-378, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674269

RESUMEN

Deoxycholic acid (DCA, 3α, 12α-dihydroxy-5ß-cholan-24-oic acid) is the major circulating secondary bile acid, which is synthesized by gut flora in the lower gut and selectively oxidized by CYP3A into tertiary metabolites, including 1ß,3α,12α-trihydroxy-5ß-cholan-24-oic acid (DCA-1ß-ol) and 3α,5ß,12α-trihydroxy-5ß-cholan-24-oic acid (DCA-5ß-ol) in humans. Since DCA has the similar exogenous nature and disposition mechanisms as xenobiotics, this work aimed to investigate whether the tertiary oxidations of DCA are predictive of in vivo CYP3A activities in beagle dogs. In vitro metabolism of midazolam (MDZ) and DCA in recombinant canine CYP1A1, 1A2, 2B11, 2C21, 2C41, 2D15, 3A12, and 3A26 enzymes clarified that CYP3A12 was primarily responsible for either the oxidation elimination of MDZ or the regioselective oxidation metabolism of DCA into DCA-1ß-ol and DCA-5ß-ol in dog liver microsomes. Six male dogs completed the CYP3A intervention studies including phases of baseline, inhibition (ketoconazole treatments), recovery, and induction (rifampicin treatments). The oral MDZ clearance after a single dose was determined on the last day of the baseline, inhibition, and induction phases, and subjected to correlation analysis with the tertiary oxidation ratios of DCA detected in serum and urine samples. The results confirmed that the predosing serum ratios of DCA oxidation, DCA-5ß-ol/DCA, and DCA-1ß-ol/DCA were significantly and positively correlated both intraindividually and interindividually with oral MDZ clearance. It was therefore concluded that the tertiary oxidation of DCA is predictive of CYP3A activity in beagle dogs. Clinical transitional studies following the preclinical evidence are promising to provide novel biomarkers of the enterohepatic CYP3A activities. SIGNIFICANCE STATEMENT: Drug development, clinical pharmacology, and therapeutics are under insistent demands of endogenous CYP3A biomarkers that avoid unnecessary drug exposure and invasive sampling. This work has provided the first proof-of-concept preclinical evidence that the CYP3A catalyzed tertiary oxidation of deoxycholate, the major circulating secondary bile acid synthesized in the lower gut by bacteria, may be developed as novel in vivo biomarkers of the enterohepatic CYP3A activities.


Asunto(s)
Inhibidores del Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/metabolismo , Ácido Desoxicólico/metabolismo , Microsomas Hepáticos/metabolismo , Adulto , Animales , Inhibidores del Citocromo P-450 CYP3A/farmacología , Perros , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Femenino , Predicción , Moduladores del GABA/metabolismo , Moduladores del GABA/farmacología , Humanos , Cetoconazol/metabolismo , Cetoconazol/farmacología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Midazolam/metabolismo , Midazolam/farmacología , Oxidación-Reducción/efectos de los fármacos
14.
J Magn Reson Imaging ; 54(5): 1551-1559, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34060693

RESUMEN

BACKGROUND: Studies have shown that loss of sensorimotor function in spinal cord injury (SCI) leads to brain functional reorganization, which may play important roles in motor function recovery. However, the specific functional changes following SCI are still poorly understood. PURPOSE: To investigate whether there are functional reorganizations outside the sensorimotor regions after complete thoracolumbar SCI (CTSCI), and how these reorganizations are associated with clinical manifestations. STUDY TYPE: Prospective. SUBJECTS: Eighteen CTSCI patients (28-67 years of age; 16 men) and 18 age-, gender-matched healthy controls (HCs) (27-64 years of age; 16 men). FIELD STRENGTH/SEQUENCE: Resting-state functional magnetic resonance imaging (RS-fMRI) using echo-planar-imaging (EPI) sequence at 3.0 T. ASSESSMENT: Data preprocessing was performed using Data Processing Assistant for Resting-State fMRI (DPARSF). Amplitude of low-frequency fluctuations (ALFF) was used to characterize regional neural function, and seed-based functional connectivity (FC) was used to evaluate the functional integration of the brain network. STATISTICAL TESTS: Two-sample t-tests were used for ALFF and FC measures (the data conform to the normal distribution), partial correlation analysis was used to analyze the correlation between clinical and imaging indicators, and receiver operating characteristic (ROC) analysis was used to search for sensitive imaging indicators. RESULTS: Compared with HCs, CTSCI patients showed decreased ALFF in right lingual gyrus (LG), increased ALFF in right middle frontal gyrus (MFG), and decreased FC between the right LG and Vermis_3 (cluster-level FWE correction with P < 0.05). Subsequent correlation analyses revealed that decreased FC between the right LG and Vermis_3 positively correlated with the visual analog scale (VAS) (P = 0.043, r = 0.443). Finally, the ROC analysis showed that the area under the curve (AUC) of FC value between right LG and Vermis3 was 0.881. DATA CONCLUSION: These findings suggest a possible theoretical basis of the mechanism of visual-, emotion-, and cognition-related techniques in rehabilitation training for CTSCI.


Asunto(s)
Mapeo Encefálico , Traumatismos de la Médula Espinal , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Traumatismos de la Médula Espinal/diagnóstico por imagen
15.
Med Sci Monit ; 27: e930363, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34103464

RESUMEN

BACKGROUND The aim of this prospective study was to compare transcranial direct current stimulation (tDCS) plus electroacupuncture with standard analgesia in patients after total knee arthroplasty (TKA) to determine the effects on rehabilitation and functional recovery. MATERIAL AND METHODS Eighty patients with osteoarthritis of the knee who underwent TKA were included in the study. They were divided into experimental (n=40) and control groups (n=40) according to postoperative analgesia method. The control group received multimodal analgesia after TKA and the experimental group received additional tDCS plus electroacupuncture. Postoperative pain, knee function, and quality of life were compared between the 2 groups. RESULTS Compared with the control group, the experimental group had significantly lower visual analog scale scores at 3 and 7 days and 3 and 6 weeks after TKA (P<0.05). At 6 weeks after TKA, knee injury and osteoarthritis outcome and Hospital for Special Surgery scores and maximum knee flexion in the experimental group were significantly better than those in the control group (P<0.05). In the experimental group compared with the control group, the Short Form-36 Health Survey score also was significantly increased (P<0.05). CONCLUSIONS The findings from this study showed that tDCS plus electroacupuncture effectively reduced pain after TKA and improved rehabilitation and functional recovery.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/rehabilitación , Manejo del Dolor/métodos , Estimulación Transcraneal de Corriente Directa/métodos , Anciano , Analgesia/métodos , Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides , Electroacupuntura/métodos , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/terapia , Periodo Posoperatorio , Estudios Prospectivos , Calidad de Vida , Rango del Movimiento Articular/fisiología , Recuperación de la Función/fisiología
16.
J Adv Nurs ; 77(4): 1772-1782, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33305491

RESUMEN

AIMS: To determine job stress among Chinese operating room nurses, test the mediating effect of burnout and verify the moderating effect of over-commitment between job stress and mental health. DESIGN: A descriptive, cross-sectional study. METHODS: A multistage sampling method was adopted. First, a random sampling method was used to select 30 tertiary hospitals in Beijing, after which 509 operating room nurses were selected by convenience sampling from March-June 2017. Self-administered questionnaires were used to evaluate job stress, burnout, and organizational commitment among participants. Multiple-group path analysis was used to test the mediating effect and the moderating effect. RESULTS: Of all nurses, 70.3% were in a state of job stress, which had negative effects on organizational commitment mediated by emotional exhaustion and depersonalization. The result of multiple-group path analysis showed that the path coefficients are different between the low and high groups of over-commitment. When facing job stress, operating room nurses with low over-commitment were more likely to have emotional exhaustion (ß = 0.750 vs. 0.602), while those with high over-commitment were more likely to have low organizational commitment (ß = -0.641 vs. -0.594). CONCLUSION: The job stress of operating room nurses in China was high. Burnout played a mediating role between job stress and organizational commitment. Over-commitment played a moderating role in the relationship among job stress, burnout, and organizational commitment. IMPACT: This study analysed the relationship among operating room nurses' job stress, burnout, and organizational commitment. The findings provided confirmatory support on the mediated effect of burnout between job stress and organizational commitment and the moderation effect of over-commitment. Different measures are needed to reduce job stress, as for easing burnout and improving organizational commitment among different groups of nurses.


Asunto(s)
Agotamiento Profesional , Enfermeras y Enfermeros , Estrés Laboral , China , Estudios Transversales , Humanos , Satisfacción en el Trabajo , Quirófanos , Encuestas y Cuestionarios
17.
Int J Psychol ; 56(5): 783-790, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33855703

RESUMEN

Distraction tasks are known to affect the unconscious-thought (UT) effect. However, the relationship between two task types, namely distraction and target tasks, and their effect on UT effect have not been examined in previous studies. In this study, we assessed whether simultaneously performing dissimilar distraction and target tasks are beneficial to information processing by UT. In Experiment 1, the target task was an Alternate Use Task (speech task). For the similar-task test, the UT group was assigned the speech 1-back task (speech task) as the distraction task; for the dissimilar-task test, the UT group was assigned the spatial 1-back task (spatial task) as the distraction task. The results of the experiment revealed that under dissimilar tasks, the UT group not only provided more answers but also provided answers that were more novel. For Experiment 2, the target task was changed to Creative Mental Synthesis Task (spatial task) to replicate the results of Experiment 1. The results demonstrated that the dissimilarity between the distraction and target tasks facilitates the UT.


Asunto(s)
Sesgo Atencional , Habla , Pensamiento , Inconsciencia/psicología , Femenino , Humanos , Masculino
18.
Biotechnol Bioeng ; 117(7): 2165-2176, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32270472

RESUMEN

Diverse applications of bacterial cellulose (BC) have different requirements in terms of its structural characteristics. culturing Komagataeibacter xylinus CGMCC 2955, BC structure changes with alterations in oxygen tension. Here, the K. xylinus CGMCC 2955 transcriptome was analyzed under different oxygen tensions. Transcriptome and genome analysis indicated that BC structure is related to the rate of BC synthesis and cell growth, and galU is an essential gene that controls the carbon metabolic flux between the BC synthesis pathway and the pentose phosphate (PP) pathway. The CRISPR interference (CRISPRi) system was utilized in K. xylinus CGMCC 2955 to control the expression levels of galU. By overexpressing galU and interfering with different sites of galU sequences using CRISPRi, we obtained strains with varying expression levels of galU (3.20-3014.84%). By testing the characteristics of BC, we found that the porosity of BC (range: 62.99-90.66%) was negative with galU expression levels. However, the crystallinity of BC (range: 56.25-85.99%) was positive with galU expression levels; galU expression levels in engineered strains were lower than those in the control strains. Herein, we propose a new method for regulating the structure of BC to provide a theoretical basis for its application in different fields.


Asunto(s)
Proteínas Bacterianas/genética , Celulosa/genética , Gluconacetobacter xylinus/genética , UTP-Glucosa-1-Fosfato Uridililtransferasa/genética , Sistemas CRISPR-Cas , Celulosa/química , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Regulación hacia Abajo , Transcriptoma
19.
Cell Mol Biol (Noisy-le-grand) ; 66(6): 34-40, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33040782

RESUMEN

This experiment aimed to explore the curative effect of Tuling Wendan Decoction combined with flunarizine on migraine patients and the intervention effect on serum cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), nitric oxide(NO) levels. For this purpose, from January 2019 to January 2020, 96 patients with migraine in our hospital were selected as the research object. Using a simple randomization method, patients who meet the criteria were assigned 1:1, and each patient was assigned a random number, of which the number 1 to 48 were the observation group, and the number 49 to 96 were the control group. The control group was treated with flunarizine, and the observation group was treated with Tuling Wendan Decoction combined with flunarizine. Comparing the efficacy, incidence of adverse reactions, the incidence of headache, cerebral blood flow rate [basal artery (BA), vertebral artery (VA), middle cerebral artery (MCA)], vascular endothelial function (serum COX-2, ET-1, NO levels), neurological function [5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene-related peptide (CGRP)] before treatment, 4 weeks and 8 weeks after treatment between the two groups. The results for efficacy showed that after 8 weeks of treatment, the total effective rate of the observation group (93.75%) was higher than that of the control group (77.08%, P<0.05). In regards to the situation of headache attack, the number of headache attacks, duration, pain degree and accompanying symptom scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group (P<0.05). Results of cerebral blood flow velocity showed that the blood flow velocity of BA, VA, MCA in the observation group was lower than that in the control group after 4 and 8 weeks of treatment (P<0.05). Vascular endothelial function results indicated that the serum COX-2 and ET-1 levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum NO levels were higher than that of the control group (P<0.05). The serum BDNF and CGRP levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum 5-HT levels were higher than the control group (P<0.05). The incidence of adverse reactions between the two groups was not statistically significant (P>0.05). It was concluded that Tuling Wendan Decoction combined with flunarizine is the first treatment for migraine, with definite curative effect and can effectively improve the onset of headache, reduce the speed of cerebral blood flow, regulate vascular endothelial function and nerve function, and ensure safety.


Asunto(s)
Ciclooxigenasa 2/sangre , Medicamentos Herbarios Chinos/uso terapéutico , Endotelina-1/sangre , Flunarizina/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Óxido Nítrico/sangre , Adulto , Circulación Cerebrovascular/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/sangre , Adulto Joven
20.
Neural Plast ; 2020: 2796571, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32211038

RESUMEN

Objective: To investigate the reorganization of insular subregions in individuals suffering from neuropathic pain (NP) after incomplete spinal cord injury (ISCI) and further to disclose the underlying mechanism of NP. Method: The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all individuals were obtained using a 3.0 Tesla MRI system. A comparative analysis of structure and function connectivity (FC) with insular subareas as seeds in 10 ISCI individuals with below-level NP (ISCI-P), 11 ISCI individuals without NP (ISCI-N), and 25 healthy controls (HCs) was conducted. Associations between the structural and functional alteration of insula subregions and visual analog scale (VAS) scores were analyzed using the Pearson correlation in SPSS 20. Results: Compared with ISCI-N patients, when the left posterior insula as the seed, ISCI-P showed increased FC in right cerebellum VIIb and cerebellum VIII, Brodmann 37 (BA 37). When the left ventral anterior insula as the seed, ISCI-P indicated enhanced FC in right BA18 compared with ISCI-N patients. These increased FCs positively correlated with VAS scores. Relative to HCs, ISCI-P presented increased FC in the left hippocampus when the left dorsal anterior insula was determined as the seed. There was no statistical difference in the volume of insula subregions among the three groups. Conclusion: Our study indicated that distinctive patterns of FC in each subregion of insula suggest that the insular subareas participate in the NP processing through different FC following ISCI. Further, insula subregions could serve as a therapeutic target for NP following ISCI.


Asunto(s)
Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Neuralgia/patología , Neuralgia/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Adulto , Anciano , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Neuralgia/etiología , Adulto Joven
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