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1.
Biol Pharm Bull ; 44(7): 902-909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193687

RESUMO

Local anesthetic toxicity is closely related to neuronal death and activation of the inflammatory response. Dexmedetomidine (Dex) is an adrenergic α2 receptor agonist that can reduce the neurotoxicity induced by lidocaine. It also has anti-inflammatory effects. However, the mechanism underlying the neuroprotective effects of Dex against lidocaine-induced toxicity remains to be defined. We hypothesized that Dex exerts its neural protective effect through inhibiting inflammasome activation and through anti-pyroptosis effects against local anesthetic-induced nerve injury. In a rat model of lidocaine-induced spinal cord injury, we studied the protective effect of Dex on lidocaine-induced changes in spinal cord function, inflammasome formation and pyroptosis, pro-inflammatory cytokine expression, and protein kinase C (PKC)-δ phosphorylation. Dex reduced lidocaine-induced neurotoxicity and inhibited PKC-δ phosphorylation in the spinal cord of rats. Furthermore, Dex inhibited pyroptosis and inflammasome formation (caspase-1, NLRP3, and apoptosis-associated speck-like protein (ASC)). Finally, Dex attenuated interleukin (IL)-1ß and IL-18 expression, as well as microglia response. In conclusion, Dex can reduce the severity of lidocaine-induced spinal cord injury in rats by inhibiting priming and inflammasome activation and reducing pyroptosis via PKC-δ phosphorylation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34195941

RESUMO

Suaeda salsa (L.) Pall., a typical halophyte plant in the Yellow River estuary, has high enrichment capacity for heavy metals. However, few studies have investigated the Cd absorption characteristics of S. salsa under different sediment burial and exogenous Cd input conditions, especially following the water-sediment regulation scheme (WSRS), which brought sediment burial and exogenous substances to the estuary. So, we established a greenhouse pot culture experiment with four sediment burial depths (0 cm, 3 cm, 6 cm, and 12 cm) and exogenous Cd input levels (0 mg·kg-1, 0.5 mg·kg-1, 1.0 mg·kg-1, and 1.5 mg·kg-1) and analyzed the leaf, stem, root, and total biomass; leaf, stem, and root Cd content; and storage, sediment Cd content, accumulation factor, root/leaf (R/L), root/stem (R/S), and stem/leaf (S/L) ratios to study the Cd absorption characteristics of S. salsa under the different sediment burial and exogenous Cd input. Results showed that high Cd content in roots, stems, and leaves was harmful to S. salsa growth, and then led to a decrease in biomass (characterized by stem, leaf, and total biomass). Suaeda salsa exhibited a survival strategy to deal with Cd toxicity, which involved the roots absorbing Cd from the sediment and storing it in stems and leaves (stem and leaf Cd content peaked at 0.5 mg·kg-1 Cd input) at low Cd input, whereas roots stored more Cd and reduced Cd transport to stems and leaves at high Cd input. Therefore, we observed the maximum value of leaf (500.63 ± 19.15 g·m-2), stem (648.22 ± 50.08 g·m-2), and total biomass (1246.92 ± 55.49 g·m-2) in the treatment with 1.5 mg·kg-1 Cd input and 3-cm sediment depth due to the Cd content in leaves and stems being relatively low. The accumulation factors of leaves, stems, and roots varied (0.39-0.99, 0.19-2.58, and 0.80-20.45, respectively), and most of the accumulation factors for roots and leaves and the R/L and R/S ratios were >1, which indicated that S. salsa had high enrichment levels of Cd, which mostly accumulated in the roots. Shallow or moderate burial depth was beneficial to S. salsa growth, but sediment burial was not beneficial to Cd absorption because the sum of leaf, stem, and root Cd storage was higher at 0-cm depth compared with the other depths. Variance analysis showed that the influence of Cd input on leaf, stem, root, and sediment Cd content and stem and root Cd storage was significant (P < 0.05), whereas sediment burial, interaction of sediment burial and Cd input on Cd content, storage, and biomass were not significant (P > 0.05). Therefore, we concluded that more attention should be paid to the control of sediment burial and heavy metal input, especially during the WSRS, in the Yellow River estuary.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34310897

RESUMO

Biochanin A is a natural plant estrogen, with various biological activities such as anti-apoptosis, anti-oxidation and suppression of inflammatory. In this study, we investigated the protective effects of biochanin A on AngⅡ-induced dopaminergic neurons damage in vivo and molecular mechanisms. Spontaneous activity and motor ability of mice among groups was detected by open-field test and swim-test. The expression of TH, LC3BⅡ/LC3BⅠ, Beclin-1, P62, p-FoxO3a / FoxO3a, FoxO3 and Endophilin A2 were determined by western blot and immunohistochemistry or immunofluorescence staining. Our results showed that AngⅡ treatment significantly increased the behavioral dysfunction of mice and DA neurons damage. Meanwhile, AngⅡ treatment increased the expression of LC3BⅡ/LC3BⅠ, Beclin-1, P62 and FoxO3a and decreased the expression of Endophilin A2 and p-FoxO3a / FoxO3a, however, biochanin A treatment alleviate these changes. In summary, these results suggest that biochanin A exerts protective effects on AngⅡ-induced mouse model may be related to regulating Endophilin A2, FoxO3a and autophagy-related proteins. However, the specific mechanism is not yet clear and needs further study.

4.
Schizophr Bull ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313787

RESUMO

OBJECTIVES: Patients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification. METHODS: In total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA). RESULTS: All HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions. CONCLUSIONS: HRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.

5.
Plant Physiol Biochem ; 166: 712-722, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34214781

RESUMO

Phosphorus (P) and nitrogen (N) are both essential macronutrients for maintaining plant growth and development. In rice (Oryza sativa L.), OsPHR3 is one of the four paralogs of PHR1, which acts as a central regulator of phosphate (Pi) homeostasis, as well being involved in N homeostasis. However, the functions of OsPHR3 in N utilization under different Pi conditions have yet to be fully studied. In this study, we aimed to dissect the effect of OsPHR3-overexpression on N utilization under Pi deficient regimes. Biochemical, molecular and physiological assays were performed to determine the N-influx, translocation, and accumulation in OsPHR3-overexpressing rice lines, grown under Pi-sufficient and -deficient conditions, in both hydroponic and soil systems. Furthermore, important agronomic traits of these plants were also evaluated. The overexpression of OsPHR3 increased N uptake under Pi stress regimes. Increased N uptake also elevated total N concentrations in these plants by inducing N transporter genes expression. Furthermore, overexpression of OsPHR3 increased N use efficiency, 1000-grain weight and grain yield under different Pi conditions. We established new findings that OsPHR3-overexpression facilitates N utilization under Pi deficient conditions. This will help achieving higher yields by coordinating the utilization of N and P.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 371-381, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238413

RESUMO

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With P<0.05 and |log2FC|>1 as the thresholds, we used GEO2R and Venn Diagram Software to filter out the common significant differentially expressed genes(DEGs).Cytoscape 3.6.1 plug-ins CytoHubba and molecular complex detection(MCODE)were used to screen out the hub genes and modules of DEGs.In addition, survival analysis of DEGs was performed by gene expression profiling(GEPIA), and Human Protein Atlas(HPA)were used to examine the protein expression levels of key genes in normal liver tissue and liver cancer tissue.Results There were 45 obviously up-regulated genes and 132 down-regulated genes, and MCODE identified 13 clusters.The cluster 1 and cluster 2 with higher scores included 16 genes and 13 genes, respectively.Among the 32 significant DEGs, IGFALS, HGFAC, CYP3A4, SLC22A1, TAT and CYP2E1 demonstrated significantly higher expression levels in liver tissue than in other organs.The HPA immunohistochemistry(IHC)data showed that the expression levels of IGFALS, CYP3A4, SLC22A1 and CYP2E1 in liver cancer tissue were significantly down-regulated and related to the low overall survival rate of patients.Conclusion The liver tissue-specific genes IGFALS, CYP3A4, SLC22A1 and CYP2E1 are under-expressed in liver cancer and associated with poor prognosis, which may be potential biomarkers and prognostic indicators for liver cancer.


Assuntos
Citocromo P-450 CYP2E1 , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Biologia Computacional , Citocromo P-450 CYP3A , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Mapas de Interação de Proteínas
7.
Sci Rep ; 11(1): 14233, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244586

RESUMO

The myodural bridge (MDB) is a dense connective tissue bridge connecting the suboccipital muscles to the spinal dura mater, and it has been proven to be a normal common existing structure in humans and mammals. Some scholars believe that the suboccipital muscles can serve as a dynamic cerebrospinal fluid (CSF) pump via the MDB, and they found head rotations promote the CSF flow in human body, which provided evidence for this hypothesis. Head movement is a complex motion, but the effects of other forms of head movement on CSF circulation are less known. The present study explored the effects of head-nodding on CSF circulation. The CSF flow of 60 healthy volunteers was analyzed via cine phase-contrast magnetic resonance imaging at the level of the occipitocervical junction before and after one-minute-head-nodding period. Furthermore, the CSF pressures of 100 volunteers were measured via lumbar puncture before and after 5 times head-nodding during their anesthetizing for surgical preparation. As a result, it was found that the maximum and average CSF flow rates at the level of the upper border of atlas during ventricular diastole were significantly decreased from 1.965 ± 0.531 to 1.839 ± 0.460 ml/s and from 0.702 ± 0.253 to 0.606 ± 0.228 ml/s respectively. In the meantime, the changes in the ratio of cranial and caudal orientation of the net flow volume were found differed significantly after the one-minute-head-nodding period (p = 0.017). And on the other hand, the CSF pressures at the L3-L4 level were markedly increased 116.03 ± 26.13 to 124.64 ± 26.18 mmH2O. In conclusion, the head-nodding has obvious effects on CSF circulation and head movement is one of the important drivers of cerebrospinal fluid circulation. We propose that the suboccipital muscles, participating in various head movements, might pull the dura sac via the myodural bridge, and thus, head movement provides power for the CSF circulation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34204145

RESUMO

Depressive symptoms are a common mental health problem among adolescents, which may affect their physical and mental health development and impose heavy burdens on individual families and society. This study aimed to examine the associations between sleep duration, academic pressure, and depressive symptoms among Chinese adolescents and to construct the mediation model to explore the mediating effect of sleep duration. The data are from the China Family Panel Studies (CFPS). Methodologically, the aforementioned associations were explored by constructing a structural equation model and applying multivariate multilevel logistic regression. In this study, we found that approximately 6.49% of the 3724 Chinese adolescents had depressive symptoms. Sleep duration of <6 h/night (OR = 2.39, 95%CI = 1.33-4.32) and high/maximum academic pressure (high: OR = 1.43, 95%CI = 1.02-1.99; maximum: OR = 2.43, 95%CI = 1.58-3.73) were both associated with an increased risk of depressive symptoms in adolescents. Meanwhile, the multiplicative interaction between sleep duration and academic pressure was significantly associated with depressive symptoms in adolescents (p < 0.001). The sleep duration played a partial mediating role in the relationship between academic pressure and depressive symptoms (a*b = 0.006, 95%BootCI = 0.001-0.012). Our study highlights that it is essential to mitigate the academic pressure of adolescents to increase their sleep duration and further reduce the occurrence of depressive symptoms by adopting corresponding preventive measures.


Assuntos
Depressão , Saúde Mental , Adolescente , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Depressão/epidemiologia , Humanos , Sono
9.
Ginekol Pol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263914

RESUMO

OBJECTIVES: To investigate the mechanism of astragaloside IV (AS-IV) inhibiting the invasion and metastasis of vulvar squamous cell carcinoma (VSCC). MATERIAL AND METHODS: MTT and plate colony-formation assays were used to examine the cell proliferation of VSCC (SW962 cell line). Transwell and scratch wound-healing assays were used to analyse cell migration and invasion. Western blot was used to detect the expression of relevant proteins in terms of cell proliferation, invasion and metastasis, as well as the TGF-ß1/FAK/AKT signaling pathway. RESULTS: The results showed that AS-IV inhibited the proliferation of SW962 cells in a concentration-dependent manner, as demonstrated by the upregulation of P53 and P21 expression and the downregulation of cyclin D1 expression. AS-IV decreased the ability of cell invasion and metastasis by the downregulation of MMP-2 and MMP-9 expression. When TGF-ß1 was added to SW962 cells, the expression of the N-cadherin and Vimentin were upregulated and that of the E-cadherin was downregulated. Subsequently, fibroblast-like elongated spindle-shaped cells appeared, which suggests that TGF-ß1 could induce EMT in SW962 cells. Furthermore, the expression of p-FAK, p-AKT, MMP-2 and MMP-9 were upregulated. The expression of these proteins exhibited the opposite effect after AS-IV intervention. Cell invasion and metastasis were suppressed. CONCLUSIONS: AS-IV inhibits cell invasion and metastasis in VSCC through the TGF-ß1/FAK/AKT signalling pathway.

10.
Biomed Environ Sci ; 34(6): 493-498, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284858

RESUMO

We aimed to assess the risks of Cryptosporidium and Giardia infections associated with drinking water for local residents, based on a quantitative microbial risk assessment, in three densely populated regions of China. In total, 45 source water samples and 45 treated water samples were collected from June to December 2014. Five Cryptosporidium-positive samples and 5 Giardia-positive samples were found. The annual probability of infection for individuals in Jintan (6.27 × 10 -4-2.05 × 10 -3 for Cryptosporidium and 7.18 × 10 -4-2.32 × 10 -3 for Giardia), Ezhou (6.27 × 10 -4-1.10 × 10 -2 for Cryptosporidium and 3.65 × 10 -4-1.20 × 10 -3 for Giardia), and Binyang (3.79 × 10 -4-1.25 × 10 -3 for Cryptosporidium) exceeded the tolerable risk of infection of 10 -4 set by the United States Environmental Protection Agency. Moreover, the corresponding disease burdens of cryptosporidiosis and giardiasis, due to direct drinking and residual water in these regions, exceeded the threshold of 10 -6 disability-adjusted life years per person per year set by the World Health Organization. These results provide insights into strategies to improve the safety of drinking water.

11.
Sci Rep ; 11(1): 14658, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282232

RESUMO

The aim of the study was to assess longitudinal changes in the spatial relationship of the choroidal vasculature to retinal vasculature in myopic eyes. In the population-based longitudinal Beijing Eye Study in 2001/2011, we examined all highly myopic eyes with assessable fundus photographs and a randomized group of non-highly myopic. Using fundus photographs, we qualitatively assessed changes in the location of major choroidal vessels in relationship to retinal vessels. The study consisted of 85 highly myopic eyes (58 participants;age:64.8 ± 9.4 years) and 85 randomly selected non-highly myopic eyes. A choroidal shift in relationship to the retinal vessels was detected more often in the highly myopic group than the non-highly myopic group (47/85 (55%) vs 6/85 (7%); P < 0.001). In the highly myopic group, the choroidal vessel shift occurring on the disc-fovea line in 39 (44%) eyes, was similar to, or smaller than, the enlargement in gamma zone width in 26 (67%) eyes and in 11 (28%) eyes respectively. The choroidal vessel shift was larger (P = 0.002) in eyes without choroidal vessels in gamma zone than in eyes with large choroidal vessels in gamma zone. In 14 (17%) eyes, a localized centrifugal choroidal shift was observed in association with an increase in the stage of myopic maculopathy. The results suggest that highly myopic eyes show a change in the position of large choroidal vessels in relationship to retinal vessels, in association with development or enlargement of gamma zone and an increase in the stage of myopic maculopathy.

12.
Transl Vis Sci Technol ; 10(8): 17, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34264294

RESUMO

Purpose: Nonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy in those older than 50 years. There is no blood diagnostic test or efficient treatment for NAION. We investigated the suitability of blood inflammatory proteins as biomarkers and therapeutic targets of NAION. Methods: We conducted an exploratory, cross-sectional case-control study including 18 patients with NAION (n = 5 acute, and n = 13 chronic) and 9 controls. NAION was confirmed by clinical examination and optical coherence tomography. Subjects underwent peripheral blood collection; plasma was isolated within 2 hours and analyzed using a 76-plex array of cytokines, chemokines, and growth factors. Results: In acute NAION, there was increased peripapillary retinal thickness on optical coherence tomography consistent with optic disc edema. Plasma profiling revealed dramatic changes in inflammatory proteins in NAION. Statistical analysis generated a list of 20 top-ranked molecules in NAION, with 15% overlap in acute and chronic NAION. Principal component analysis, hierarchical clustering, and Spearman correlation generally segregated controls, acute and chronic NAION, with some overlap. Longitudinal data from one patient demonstrated an evolving inflammatory pattern from acute to chronic NAION. In acute NAION, Eotaxin-3, MCP-2, TPO, and TRAIL were the top biomarker candidates. In chronic NAION, IL-1α and CXCL10 emerged as the strongest therapeutic targets. Conclusions: Post-NAION inflammation occurs in both acute and chronic NAION. Statistical analysis of plasma profile changes generated a list of 20 potential biomarker and therapeutic targets of NAION. Translational Relevance: We identified blood molecular targets to improve NAION diagnosis and treatment.

13.
Phytochemistry ; 190: 112866, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34271299

RESUMO

Seven previously undescribed diterpenoid alkaloids, eight reaction products and thirteen known compounds were isolated from the whole plant of Delphinium grandiflorum L. (Ranunculaceae). Grandiflonines A and B have an unprecedented C20-diterpenoid alkaloid skeleton, which features inversion of the configuration of C-18. Their structures were determined by comprehensive analyses of spectroscopic data, X-ray diffraction and Mosher's method. The probable biosynthetic pathway of grandiflonine A was discussed. Additionally, the analgesic activity and anti-inflammatory activity by inhibition of NO production were evaluated. Among them, deoxylappaconitine (ED50 = 0.35 mg/kg, TI = 46.22) showed significant analgesic activity that was superior to the reference drug lappaconitine (ED50 = 3.5 mg/kg, TI = 3.34).

14.
Parkinsonism Relat Disord ; 89: 98-104, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271425

RESUMO

BACKGROUND: Reduced diffusion along perivascular spaces in adults with Alzheimer's-disease-related-dementias has been reported and attributed to reduced glymphatic function. OBJECTIVES: To apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration. METHODS: 181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 T MRI. Diffusion-tensor-imaging (spatial resolution = 2x2x2 mm; b-value = 1000 s/mm2; directions = 33) measures of diffusion (mm2/s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (ALPS-index), were calculated. Regions were identified by a board-certified neuroradiologist from T1-weighted and T2-weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score. RESULTS: The ALPS-index was reduced in PD compared to ET participants (p = 0.037). No association between the ALPS-index and MCI status, but an inverse association between the ALPS-index and Fazekas score (p = 0.002), was observed. The ALPS-index was inversely associated with age (p = 0.007). CONCLUSION: Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity.

15.
Zhongguo Gu Shang ; 34(7): 650-4, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34318642

RESUMO

OBJECTIVE: To study the changes of anterior soft tissue swelling after anterior cervical subtotal corpectomy, titanium mesh fusion and internal fixation. METHODS: From November 2015 to July 2018, 151 patients with cervical spondylotic myelopathy were treated with anterior single corpectomy, titanium mesh fusion and internal fixation, including 109 males and 42 females, aged 44 to 81 (59.77±8.34) years. Through postoperative follow up observation, the C2-C7 level of anterior intervertebral space distance was measured to evaluate the changes of anterior soft tissue swelling. RESULTS: All patients were followed up for 15 to 40(28.00±3.52) months. One week after the operation, the swelling of anterior soft tissue reached the peak, and then decreased. At 8 months after the operation, the swelling of anterior soft tissue on C5, C6 and C7 plane returned to normal. At 12 months after the operation, the swelling of anterior soft tissue on C2, C3 and C4 plane returned to normal. CONCLUSION: Anterior subtotal cervical corpectomy, titanium mesh bone graft fusion and internal fixation can cause swelling of the anterior soft tissue. One week after operation, we should pay more attention to the aggravation of the swelling of the anterior soft tissue to avoid the occurrence of dysphagia, respiratory obstruction, asphyxia and other complications.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34214160

RESUMO

CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using faecal and serum metabolomics. METHODS: We analysed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density (BMD) using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in faeces (15 categories) and serum (12 categories) were further analysed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Faecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, faecal metabolomics and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

18.
Biochem Genet ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255218

RESUMO

Several microRNAs (miRNAs) and circular RNAs (circRNAs) were reported to be involved in the Docetaxel (DTX) chemoresistance of cancer treatment, but the underlying mechanisms remain to be explored. In this study, we established cellular and animal models respectively to study the effect and underlying molecular mechanisms of the dysregulation of circRNA_0006404 and circRNA_0000735 in tumor response to DTX treatment. Quantitative real-time PCR was performed to measure the expression of circRNA_0006404, miR-346, circRNA_0000735, miR-526b, Dickkopf-related protein 3 (DKK3), and Dickkopf-related protein 4 (DKK4) mRNA. The expression of circRNA_0006404 and circRNA_0000735 was remarkably suppressed and activated in DTX-treated SKOV3-R cell lines, respectively. As revealed by luciferase assays, circRNA_0006404 and circRNA_0000735 was found to be respectively targeted by miR-346 and miR-526b, while DKK3 and DKK4 were respectively targeted by miR-346 and miR-526b. Moreover, the expression of DKK3 and DKK4, which were targets of miR-346 and miR-526b, respectively, was significantly altered along with the expression of p-GP. Furthermore, circ_0006404 shRNA and circRNA_0000735 shRNA showed remarkable efficiency in stimulating the expression of circRNA_0006404, miR-346, DKK3, circRNA_0000735, miR-526b, DKK4, and p-GP in cellular and animal models. Accordingly, the cell apoptosis and proliferation were apparently changed by circ_0006404 shRNA and circRNA_0000735 shRNA in both cellular and animal models. In summary, our study found the involvement of the circRNA_0006404/miR-346/DKK3/p-GP and circRNA_0000735/miR-546b/DKK4/p-GP axis in the tumor response to DTX. Both the up-regulation of circRNA_0006404 and down-regulation of circRNA_0000735 could inhibit the expression of p-GP in vivo and ex vivo, leading to the suppressed tumor response to DTX treatment.

19.
Acad Emerg Med ; 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245632

RESUMO

BACKGROUND: Clinical decision support may improve the post-neuroimaging management of children with mild traumatic brain injuries (mTBI) and intracranial injuries. While the CHIIDA score has been proposed for this purpose, a more sensitive risk model may have broader use. Consequently, this study's objectives were to: 1) develop a new risk model with improved sensitivity compared to the CHIIDA model; and 2) externally validate the new model and CHIIDA model in a multicenter dataset. METHODS: We analyzed children ≤ 18 years-old with mTBI and intracranial injuries included in the PECARN head injury dataset (2004-2006). We used binary recursive partitioning to predict the composite outcome of neurosurgical intervention, intubation for > 24 hours due to TBI, or death due to TBI. The new model was externally validated in a separate dataset that included children treated at any one of six centers from 2006-2019. RESULTS: Based on 839 patients from the PECARN dataset, a new risk model, the KIIDS-TBI model, was developed that incorporated imaging (e.g. midline shift) and clinical (e.g. GCS score) findings. Based on the model-predicted probability of the composite outcome, three cutoffs were evaluated to classify patients as 'high risk' for level of care decisions. In the external validation dataset consisting of 1,630 patients, the most conservative cutoff (i.e. any predictor present) identified 119/119 children with the composite outcome (sensitivity 100%), but had the lowest specificity (26.3%). The other two decision-making cutoffs had worse sensitivity (94.1%-96.6%) but improved specificity (67.4%-81.3%). The CHIIDA model lacked the most conservative cutoff and otherwise showed the same or slightly worse performance compared to the other two cutoffs. CONCLUSIONS: The KIIDS-TBI model has high sensitivity and moderate specificity for risk-stratifying children with mTBI and intracranial injuries. Use of this clinical decision support tool may help improve the safe, resource-efficient management of this important patient population.

20.
Orphanet J Rare Dis ; 16(1): 314, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266467

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis. METHODS: Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04-72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1-23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3-126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy. CONCLUSIONS: Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.

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