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1.
Cell Death Dis ; 12(4): 357, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824286

RESUMO

Mesenchymal stem cells (MSCs) are one of the most widely clinically trialed stem cells, due to their abilities to differentiate into multiple cell lineages, to secrete regenerative/rejuvenative factors, and to modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSCs from 32 donors and revealed donor-dependent variations in two non-correlated properties, (1) cell proliferation, and (2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSCs. Through unbiased transcriptomic analyses, we discovered that IFN-γ and NF-κB signaling were positively associated with immune modulatory function of MSCs. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while having abolished donor-dependent variations in immune modulatory function, did not overall make different donor-derived MSCs the same at whole transcriptomic levels, demonstrating that the cells were still different in many other biological perspectives, and may not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to ensure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSCs to treat inflammation-related clinical conditions and/or autoimmune diseases.

2.
Exp Mol Med ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859350

RESUMO

Senile osteoporosis can cause bone fragility and increased fracture risks and has been one of the most prevalent and severe diseases affecting the elderly population. Bone formation depends on the proper osteogenic differentiation of bone marrow stromal cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types in the bone marrow. With aging, bone marrow provides signals that repress osteogenesis. Finding the signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the abnormal changes in BMSCs with aging are key to elucidating the mechanisms of senile osteoporosis. In a pilot experiment, we found that 4-1BBL and 4-1BB were more abundant in bone marrow from aged (18-month-old) mice than young (6-month-old) mice. Meanwhile, significant bone loss was observed in aged mice compared with young mice. However, very little data have been generated regarding whether high-level 4-1BB/4-1BBL in bone marrow was associated with bone loss in aged mice. In the current study, we found upregulation of 4-1BB in the BMSCs of aged mice, which resulted in the attenuation of the osteogenic differentiation potential of BMSCs from aged mice via the p38 MAPK-Dkk1 pathway. More importantly, bone loss of aged mice could be rescued through the blockade of 4-1BB signaling in vivo. Our study will benefit not only our understanding of the pathogenesis of age-related trabecular bone loss but also the search for new targets to treat senile osteoporosis.

3.
J Mater Chem B ; 9(16): 3489-3501, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33690737

RESUMO

Osteoporosis (OP) is a major systemic bone disease leading to an imbalance in bone homeostasis which remains a challenge in the current treatment of bone defects. Our previous studies on strontium (Sr) doping apparently stimulated osteogenesis of bioceramics, which suggested a promising strategy for the treatment of bone defects. However, the potential effects and the underlying mechanisms of Sr-doping on osteoporotic bone defects still remain unclear. Autophagy is a conventional self-degradation process of cells involved in bone homeostasis and regeneration under physiological and pathological conditions. Therefore, it is essential to design appropriate biomaterials and investigate the associated osteogenic mechanisms via autophagy. Based on this hypothesis, Sr-doped 45S5 bioglass (Sr/45S5) was fabricated, and ovariectomy bone marrow-derived mesenchymal stem cells (OVX-BMSCs) were applied as the in vitro cell culture model. First, the optimal Sr-doping concentration of 10 mol% was screened by cell proliferation, ALP staining, alizarin red S staining and the real-time PCR assay. Then, the results of western blot (WB) analysis showed that Sr-induced osteogenic differentiation of OVX-BMSCs was associated with time-dependent modulation of autophagy and related to the AKT/mTOR signaling pathway. Meanwhile, the autophagy in Sr-induced osteogenic differentiation of OVX-BMSCs was detected by WB, immunofluorescence staining and transmission electron microscopy. Furthermore, the effect of osteogenic differentiation of OVX-BMSCs has been significantly inhibited by the administration of autophagy inhibitors and the AKT/mTOR pathway inhibitors, respectively, in the early and late periods of osteogenic differentiation. Finally, the results of the model of femoral condyle defects in OVX-rats indicated that Sr10/45S5 granules remarkably enhanced bone regeneration which provided the evidences in vivo. Our research indicates that Sr-doping provides a promising strategy to promote osteogenic differentiation of OVX-BMSCs and bone regeneration in osteoporotic bone defects via early improvement of autophagy and late activation of the Akt/mTOR signaling pathway.

4.
Comput Biol Med ; 131: 104291, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33676337

RESUMO

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) is a well-established surgical treatment for patients with lumbar degenerative disc disease; however, the optimal position for the interbody fusion cage in TLIF procedures for reducing cage-related complications remains uncertain. The present study aims to compare the biomechanical effects between different cage positions in TLIF and percutaneous endoscopic-TLIF (PE-TLIF). METHOD: An intact finite element model of L3-L5 from computed tomography images of a 25-year-old healthy male without any lumbar disease was reconstructed and validated. TLIF and PE-TLIF were performed on L4-L5 with bilateral pedicle screws fixation. Two surgical finite element models were subjected to loads with six degrees of freedom. The range of motion (ROM) and von Mises stress of the implantations and endplates were measured for the anterior, middle, and posterior district and the traverse or oblique direction of the cage respectively. RESULTS: As the cage was implanted forward, the ROMs in the fused L4-L5 segments and the von Mises stress of the cage and endplates decreased while the von Mises stress of the screws increased; this was also shown in the traverse cage when compared with the oblique cage (A-90-compared with A-45- had a 31.3%, 1.7%, 12.6%, and 5.7% decrease in FL, EX, LB and AR). The ROMs (TLIF A-45 increase of 80.8%, 23.8%, and 12.2% in FL, EX, and LB when compared with PE-TLIF), cage stress, and endplate stress of PE-TLIF were lower than those of TLIF. CONCLUSIONS: Considering the ROM of the fusion segments, implanting the cage in the anterior district in the traverse direction can effectively enhance the fusion segment stiffness, thus contributing to the stability of the lumbar spine after fusion. It can also cause less cage stress and endplate stress, which indicates its beneficial effect in avoiding cage injury or subsidence. However, the higher stress of the pedicle screws and rods indicates higher failure risk. PE-TLIF had better biomechanical performance than TLIF. Therefore, it is recommended that the surgeon implant the cage in the anterior district of the L5 vertebra's upper endplate in the traverse direction using the PE-TLIF technique.

5.
Proteomics Clin Appl ; : e2000022, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33599092

RESUMO

PURPOSE: The changes of glycosylation of different IgG subclass in colorectal cancer (CRC) were rarely investigated. The authors aimed to use a simple and high-throughput analytical method to explore the changes of subclass-specific IgG glycosylation in CRC, and to find the specific glyco-biomarkers for early detection of this disease. EXPERIMENTAL DESIGN: Serum samples from 71 cancer patients and 22 benign patients with 50 age- and sex-matched healthy controls were collected from two independent cohorts. Subclass-specific IgG glycosylation was profiled by MALDI-MS followed by the structural identification through MALDI-MS/MS. The exported MS data was automatically and rapidly processed by the self-developed MATLAB code. RESULTS: Statistical analysis suggested the significantly decreased galactosylation and remarkably increased agalactosylation of IgG1 or IgG2 in the malignant transformation of CRC, which enables the differentiation between cancer patients and healthy controls. The changes of glycan features were elucidated by the exploration of individual glycopeptides, showing the biantennary fucosylated glycan without galactose (H3N4F1) or with two galactose (H5N4F1) of IgG1 and IgG2 could distinguish cancer group from both benign and control groups. CONCLUSIONS AND CLINICAL RELEVANCE: Through the simple and high-throughput procedures, this study revealed the important role of IgG glycopeptides in the premature pathology of CRC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33586540

RESUMO

The cervical spine injury is a complicated procedure in the combination of different injury loads and postures. The aim of this study is to investigate the injury mechanism considering different types of cervical curvatures subjected to contusion loads. A finite element model of a cervical spinal cord was constructed. Gray matter, white matter and pia matter were modeled and hyperelastic material properties were assigned. Convergence analysis and validation analysis were carried out. The model was simulated in 3 different spinal curvatures and loaded by 2 directions with 4 compression degrees. The maximum von Mises stress in the whole model was concentrated in the pia matter in all loading cases. When investigating spinal cord injury, the pia matter must be considered. For all three curvatures, the stress in the gray matter and white matter was higher in front-to-back loading condition than that in back-to-front loading condition. The front-to-back impact may cause a larger damage. A back-to-front load damaged the structure around the central canal and a front-to-back contusion load damaged the anterior horn of the spinal cord at most time. From the view of the maximum stress, the lordotic curvature did not show significant buffering effect. However, the pathological curvature had large areas affected and the lordotic curvature showed some benefits to some degree from the view of stress distribution.

7.
ACS Nano ; 15(2): 2812-2830, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33527830

RESUMO

Immune microenvironment amelioration and reconstruction by functional biomaterials has become a promising strategy for spinal cord injury (SCI) recovery. In this study, we evaluated the neural regeneration and immunoregulation functions of Mg/Al layered double hydroxide (Mg/Al-LDH) nanoparticles in completely transected and excised mice and revealed the immune-related mechanisms. LDH achieved significant performance in accelerating neural stem cells (NSCs) migration, neural differentiation, L-Ca2+ channel activation, and inducible action potential generation. In vivo, the behavioral and electrophysiological performance of SCI mice was significantly improved by LDH implantation, with BrdU+ endogenous NSCs and neurons clearly observed in the lesion sites. According to RNA-seq and ingenuity pathway analysis, transforming growth factor-ß receptor 2 (TGFBR2) is the key gene through which LDH inhibits inflammatory responses and accelerates neural regeneration. Significant colocalization of TGFBR2 and LDH was found on the cell membranes of NSCs both in vitro and in vivo, and LDH increased the expression of TGF-ß2 in NSCs and activated the proliferation of precursor neural cells. LDH decreased the expression of M1 markers and increased the expression of M2 markers in both microglia and bone marrow-derived macrophages, and these effects were reversed by a TGFBR2 inhibitor. In addition, as a carrier, LDH loaded with NT3 exhibited better recovery effects with regard to the basso mouse scale score, motor evoked potential performance, and regenerated neural cell numbers than LDH itself. Thus, we have developed Mg/Al-LDH that can be used to construct a suitable immune microenvironment for SCI recovery and have revealed the targeted receptor.

8.
FASEB J ; 35(3): e21392, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33577131

RESUMO

The variations and dynamics of essential and toxic metal(loid)s in patients with COVID-19 may associate with the progression and fatal outcome of the disease, which still remains to investigate. In the present study, a retrospective analysis was performed in a cohort of 306 confirmed COVID-19 patients admitted to Tongji hospital (Wuhan, China) from February 10 to March 15, 2020. Whole blood levels of essential and/or toxic metal(loid)s were analyzed, including magnesium, calcium, chromium, manganese, iron, copper, zinc, arsenic, cadmium, mercury, thallium, and lead according to the disease severity and outcome. Compared to the non-severe COVID-19 patients, severe cases showed significant higher levels of whole blood calcium, chromium, and copper, but lower levels of magnesium, manganese, iron, zinc, arsenic, thallium, and lead. These differences were further found consistently across the clinical course since the disease onset by longitudinal analysis. Among the severe patients, chromium and cadmium were higher in the deceased group compared to the recovered group, while arsenic was lower. Whole blood iron, age, and sex were determined to be independent factors associated with the disease severity, while chromium, cadmium, and the comorbidity of cardiovascular disease were determined to be independent factors associated with the mortality. These results suggest that variations of whole blood metal(loid)s may be associated with the severe illness and fatal outcome of COVID-19, which could be persistently monitored and would be helpful in the evaluation of the dynamic changes in patients with COVID-19.


Assuntos
/sangue , Metaloides/sangue , Metais/sangue , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Nat Methods ; 18(2): 212-218, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33432243

RESUMO

Exosomes have shown great potential in disease diagnostics and therapeutics. However, current isolation approaches are burdensome and suffer from low speed, yield and purity, limiting basic research and clinical applications. Here, we describe an efficient exosome detection method via the ultrafast-isolation system (EXODUS) that allows automated label-free purification of exosomes from varied biofluids. We obtained the ultra-efficient purification of exosomes by negative pressure oscillation and double coupled harmonic oscillator-enabled membrane vibration. Our two coupled oscillators generate dual-frequency transverse waves on the membranes, enabling EXODUS to outperform other isolation techniques in speed, purity and yield. We demonstrated EXODUS by purifying exosomes from urine samples of 113 patients and validated the practical relevance in exosomal RNA profiling with the high-resolution capability and high-throughput analysis.


Assuntos
Exossomos , Automação , Ensaios de Triagem em Larga Escala/métodos , Humanos , RNA/isolamento & purificação
10.
Environ Int ; 146: 106305, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395947

RESUMO

BACKGROUND: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. OBJECTIVE: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. METHODS: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose-response associations between exposures and outcomes. RESULTS: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: -0.44, -0.15 and -0.21 cm, 95% CI: -0.36, -0.07 comparing the extreme exposure groups, respectively, both p for trends < 0.01). These associations were more pronounced in girls with inverted U-shaped dose-response relationships. Maternal urinary BPA and BPF were positively related to ponderal index (0.05 g/cm3 × 100, 95% CI: 0.01, 0.09 and 0.04 g/cm3 × 100, 95% CI: 0.01, 0.08 comparing the extreme exposure groups, respectively, both p for trends = 0.02), and maternal urinary BPS was associated with shorter gestational age (-0.20 weeks, 95% CI: -0.37, -0.03 comparing the extreme exposure groups, p for trend = 0.02). These associations were only observed in girls and exhibited a linear dose-response relationship. CONCLUSIONS: Prenatal BPA, BPF, and BPS exposures were associated with detrimental effects on fetal growth parameters, and stronger effects were noted in female infants.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Fenóis , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
11.
Environ Res ; 194: 110670, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33387537

RESUMO

BACKGROUND: The dynamics of urinary trace elements in patients with COVID-19 still remains to be investigated. METHODS: A retrospective study was performed on a cohort of 138 confirmed COVID-19 patients for their urinary levels of essential and/or toxic metals including chromium, manganese, copper, arsenic, selenium, cadmium, mercury, thallium and lead according to the different disease severity (severe or non-severe) and outcome (recovered or deceased). RESULTS: Urinary concentrations of chromium, manganese, copper, selenium, cadmium, mercury and lead after creatinine adjustment were found to be higher in severe patients than the non-severe cases with COVID-19. And among the severe cases, these elements were also higher in the deceased group than the recovered group. When the weeks of the post-symptom onset were taken in account, the changes of these urinary elements were existed across the clinical course since the disease onset. These urinary elements were found to be mostly positively inter-correlated, and further positively correlated with other laboratory inflammatory parameters including serum cytokines (IL-1B, IL2R, IL6, IL8, IL10, TNFα), ferritin, and neutrophil count and white blood cell count. As a independently predictive factor, urinary creatinine-adjusted copper of ≥25.57 µg/g and ≥99.32 µg/g were associated with significantly increased risk of severe illness and fatal outcome in COVID-19, respectively. CONCLUSIONS: These results suggest abnormities in urinary levels of the trace metals were tightly associated with the severe illness and fatal outcome of COVID-19.


Assuntos
Selênio , Oligoelementos , Cádmio , Cobre , Humanos , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
Spine (Phila Pa 1976) ; 46(1): E37-E47, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991511

RESUMO

STUDY DESIGN: A retrospective data analysis was performed. OBJECTIVE: The aim of this study is to explore the significant prognostic factors and propose new nomograms to facilitate clinical decision-making. SUMMARY OF BACKGROUND DATA: Chordoma is a rare bone tumor. The clinical features and optimal therapeutic strategies are still uncertain. METHODS: Chordoma patients treated in four medical centers of mainland China before January 2015 were included. The predictors for local relapse-free survival (LRFS) and overall survival (OS) were identified by the Lasso regression and Cox proportional hazards regression model. Then the nomograms were developed. Their discrimination, calibration, and accuracy were evaluated by the C-index, calibration curve, and receiver operating characteristic curve (ROC), respectively. RESULTS: A total of 341 patients were identified and full prognostic variable data were available for 276 patients. A total of 179 patients (64.9%) experienced recurrence and 122 patients (44.2%) died of all causes with a median follow-up time of 57.5 (range, 1-325) months. We identified recurrence-relevant factors of tumor size, tumor location, histology subtype and resection method, and death-relevant factors of tumor size, tumor location, resection method, complication, and postoperative recurrence. The constructed LRFS and OS nomograms showed good calibration and discriminative ability (C index 0.79 and 0.76, respectively). The ROCs suggested decent prediction ability with the 5-year area under curve (AUC) value of 0.868 and 0.786, respectively. CONCLUSION: Based on the multicenter case series of chordoma with a relative long follow-up, we proposed two nomograms to predict the prognosis on the basis of recurrence- and death-relevant factors. These findings could be referenced in the clinical decision-making process and provide additional prognostic information for risk stratification. LEVEL OF EVIDENCE: 4.


Assuntos
Cordoma/diagnóstico , Cordoma/mortalidade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Adulto , Idoso , Área Sob a Curva , Neoplasias Ósseas/patologia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos
13.
Reprod Biomed Online ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33288478

RESUMO

RESEARCH QUESTION: Does SARS-CoV-2 infection have an effect on ovarian reserve, sex hormones and menstruation of women of child-bearing age? DESIGN: This is a retrospective, cross-sectional study in which clinical and laboratory data from 237 women of child-bearing age diagnosed with COVID-19 were retrospectively reviewed. Menstrual data from 177 patients were analysed. Blood samples from the early follicular phase were tested for sex hormones and anti-Müllerian hormone (AMH). RESULTS: Among 237 patients with confirmed COVID-19, severely ill patients had more comorbidities than mildly ill patients (34% versus 8%), particularly for patients with diabetes, hepatic disease and malignant tumours. Of 177 patients with menstrual records, 45 (25%) patients presented with menstrual volume changes, and 50 (28%) patients had menstrual cycle changes, mainly a decreased volume (20%) and a prolonged cycle (19%). The average sex hormone and AMH concentrations of women of child-bearing age with COVID-19 were not different from those of age-matched controls. CONCLUSIONS: Average sex hormone concentrations and ovarian reserve did not change significantly in COVID-19 women of child-bearing age. Nearly one-fifth of patients exhibited a menstrual volume decrease or cycle prolongation. The menstruation changes of these patients might be the consequence of transient sex hormone changes caused by suppression of ovarian function that quickly resume after recovery.

14.
Cell Death Dis ; 11(12): 1058, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33311478

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aß containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Aß production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of δ-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, δ-secretase facilitates AD pathogenesis independent of any patient-derived mutation.


Assuntos
Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/complicações , Animais , Disfunção Cognitiva/complicações , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Humanos , Inflamação/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Sinapses/metabolismo , Sinapses/ultraestrutura
15.
J Nutr ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188401

RESUMO

BACKGROUND: Vitamin D might have beneficial potential in influencing the natural history of the coronavirus disease 2019 (COVID-19) due to its immunomodulatory and anti-inflammatory properties. OBJECTIVE: The aim was to investigate whether vitamin D deficiency is associated with COVID-19 incidence and disease severity in Chinese people. METHODS: In a cross-sectional study we retrospectively analyzed 335 COVID-19 patients (median: 56.0; IQR: 43.0-64.0 y) who were admitted to the Wuhan Tongji Hospital between 27 February and 21 March 2020. We also included an age- and sex-matched population of 560 individuals (median: 55; IQR: 49.0-60.0 y) who underwent the physical examination program. Their serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during the same period from 2018-2019. Serum 25(OH)D concentrations were measured for all COVID-19 patients on admission. Severity of COVID-19 was determined based on the level of respiratory involvement. A general linear model with adjustment for covariates was used to compare 25(OH)D concentrations between the COVID-19 and 2018-2019 control groups. Adjusted ORs with 95% CIs for associations between vitamin D status and COVID-19 severity were estimated via multivariable logistic regression. RESULTS: In the general linear model adjusted for age, sex, comorbidities, and BMI, serum 25(OH)D concentrations were significantly lower among COVID-19 patients than the 2018-2019 controls [ln transformed values of 3.32 ± 0.04 vs. 3.46 ± 0.022 ln (nmol/L), P = 0.014]. Multivariable logistic regression showed that male sex (OR: 2.26; 95% CI: 1.06, 4.82), advanced age (≥65 y) (OR: 4.93; 95% CI: 1.44, 16.9), and vitamin D deficiency (<30 nmol/L) (OR: 2.72; 95% CI: 1.23, 6.01) were significantly associated with COVID-19 severity (all P < 0.05). CONCLUSIONS: These findings suggested that vitamin D deficiency impacts COVID-19 hospitalization and severity in the Chinese population.

16.
Dose Response ; 18(4): 1559325820946918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192200

RESUMO

Introduction: Osteoarthritis (OA) is associated with deregulation of various miRNAs (miRs). The present study reported protective effect of miR-152 in osteoarthritis. Methods: Tissue cartilage tissues of OA and normal subjects were used, rat model of anterior cruciate ligament transection (ACLT) was developed. Cartilage study was done by Safranin O-fast green, histological and immunostaining. The chondrocytes were isolated from tissues and were treated with IL-1ß and infected with miR-152 or TCF-4 cloned lentiviral vectors. MTT assay was done for cell viability, apoptosis by Annexin-V-FITC staining. Expressions of proteins by western blot assay. Collagen-II assay was done by immunofluroscent assay. Luciferase activity by dual luciferase reporter assay. Results: Upregulation of miR-152 improved viability of chondrocytes, decreased apoptosis and balanced the catabolic and anabolic factors of extracellular matrix in vitro. Injecting miR-152 lentivirus in rats improved articular cartilage in osteoarthritis ACLT rats. Bioinformatics analysis suggested TCF-4 as favorable target gene of miR-152, having binding site on the 3'UTR region of TCF-4 mRNA and inhibited the expression of TCF-4. Osteoarthritis tissue cartilage both from humans and rats showed expression of miR-152 inversely linked with expression of TCF-4. Conclusion: Present study concludes miR-152 diminished the progression of osteoarthritis partially by inhibiting the expression of TCF-4.

17.
FEBS J ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098359

RESUMO

Up to 10-20% of patients with coronavirus disease 2019 (COVID-19) develop a severe pulmonary disease due to immune dysfunction and cytokine dysregulation. However, the extracellular proteomic characteristics in respiratory tract of these critical COVID-19 patients still remain to be investigated. In the present study, we performed a quantitative proteomic analysis of the bronchoalveolar lavage fluid (BALF) from patients with critical COVID-19 and from non-COVID-19 controls. Our study identified 358 differentially expressed BALF proteins (P < 0.05), among which 41 were significantly changed after using the Benjamini-Hochberg correction (q < 0.05). The up-regulated signaling was found to be mainly involved in inflammatory signaling and response to oxidative stress. A series of increased extracellular factors including Tenascin-C (TNC), Mucin-1 (KL-6 or MUC1), Lipocalin-2 (LCN2), periostin (POSTN), Chitinase 3-like 1 (CHI3L1 or YKL40), and S100A12, and the antigens including lymphocyte antigen 6D/E48 antigen (LY6D), CD9 antigen, CD177 antigen, and prostate stem cell antigen (PSCA) were identified, among which the proinflammatory factors TNC and KL-6 were further validated in serum of another thirty-nine COVID-19 patients and healthy controls, showing high potentials of being biomarkers or therapeutic candidates for COVID-19. This BALF proteome associated with COVID-19 would also be a valuable resource for researches on anti-inflammatory medication and understanding the molecular mechanisms of host response. DATABASE: Proteomic raw data are available in ProteomeXchange (http://proteomecentral.proteomexchange.org) under the accession number PXD022085, and in iProX (www.iprox.org) under the accession number IPX0002429000.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33091677

RESUMO

Serotonin (5-hydroxytryptamine, 5-HT) is readily secreted in patients with carcinoid tumors, especially arising from the midgut. Although serotonin assay in human plasma or whole blood has been extensively studied, serotonin assay in human serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has received much less attention. In this study, a simple and reliable LC-MS/MS method based on one step protein precipitation for sample pretreatment was developed for clinical assay of serum serotonin. Namely, 150 µL of serum was mixed with 50 µL of internal standard (IS) and 200 µL of 4 wt.% 5-sulfosalicylic acid (SSA) solution for protein precipitation. The supernatant after centrifugation was analyzed directly without further treatment. This method was validated for consistent linearity from 0.94 to 240 ng/mL with CVs ≤ 11.7%, good recovery in the range of 87.5%-104%, excellent analyte stability and low carryover. No obvious matrix effect was observed. Intra- and inter-day imprecision were below 8.03% and 11.5% respectively. Dilution linearity was verified with satisfying linearly dependent coefficients (r2 = 0.9937). The reference interval of serotonin was established from 126 results derived from subjects without carcinoid tumors. Therefore, apart from development of a serum serotonin assay by the LC-MS/MS method, the reference interval (RI) of 5-HT has also been established for clinical testing in patients with carcinoid tumors. In addition, this method has been successfully used in our laboratory, indicating that this robust LC-MS/MS assay with simple sample preparation and short analysis time could offer inspiring potential for clinical testing of 5-HT in routine clinical laboratories.

19.
Curr Med Sci ; 40(5): 817-821, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123896

RESUMO

In the period of regular epidemic prevention and control of Coronavirus disease 2019 (COVID-19) in our country, work resumption has been fully advanced. But there are still new sporadic local cases and imported cases across the country. In this situation, whether kindergartens reopening will increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread still remains uncertain. We reviewed two pediatric patients with moderate COVID-19, collected the epidemiologic information and monitored the cycle threshold value of rectal specimen and the viral loads, and discussed the transmission of SARS-CoV-2 in pediatric patients and the virulence of feces in children with moderate COVID-19, in order to analyze the risk of kindergartens reopening.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Fezes/virologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Feminino , Humanos , Pandemias/estatística & dados numéricos , Pais , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Instituições Acadêmicas , Carga Viral , Eliminação de Partículas Virais
20.
Front Genet ; 11: 953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014018

RESUMO

Hereditary spherocytosis (HS) is an inherited disorder characterized by anemia, splenomegaly, and spherical-shaped erythrocytes, caused by mutations in erythrocyte membrane Protein Genes (ANK1, SPTB, SLC4A1, SPTA1, and EPB42). We investigated molecular spectrum and genotype-phenotype correlation in HS patients in Hubei province, central China. Twenty-three patients with HS were included. A next-generation sequencing (NGS) panel targeting ANK1, SPTB, SLC4A1, SPTA1, and EPB42 genes was used to screen potential variants. Sanger sequencing was applied to validate variants. Of the twenty-three patients, thirteen patients carried ANK1 variants, and ten patients harbored SPTB variants, including ten non-sense, six indel, four splice site, one start-loss, and one missense variant. Four out of twenty-two variants in our study were known, and eighteen variants were novel. Most ANK1 and SPTB variants were indel (5/12) or non-sense (7/10), respectively. Family member analysis in thirteen families showed that six variants were de novo. Variable expressivities were observed in a pair of twins with ANK1 c.341C > T variant, and two unrelated patients both carried ANK1 c.2T > A variant. Genotype-phenotype analysis found no significant difference between ANK1 and SPTB regarding the levels of Hb, RBC, MCV, MCH, and MCHC. However, variants in the ANK1 death domain were associated with lower levels of MCV and MCH compared to other ANK1 domains. In conclusion, NGS is a fast way to provide a molecular HS diagnosis. We also identified unique genetic and clinical characteristics of patients with HS in Hubei Province, China. However, a large sample size is needed to further investigate the genotype-phenotype correlation.

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