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1.
Eur J Neurol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559384

RESUMO

BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease. Although genetic factors are involved in its pathogenesis, limited evidence is available in this area. The aim of the present study was to identify the major genetic factors contributing to NMOSD in Chinese patients with aquaporin 4 (AQP4)-IgG seropositivity. METHODS: Whole-exome sequencing (WES) was performed on 228 Chinese NMOSD patients seropositive for AQP4-IgG and 1400 healthy controls in Guangzhou, South China. Human leukocyte antigen (HLA) sequencing was also utilized. Genotype model and haplotype, gene burden, and enrichment analyses were conducted. RESULTS: A significant region of the HLA composition is on chromosome 6, and great variation was observed in DQB1, DQA2 and DQA1. HLA sequencing confirmed that the most significant allele was HLA-DQB1*05:02 (p < 0.01, odds ratio [OR] 3.73). The genotype model analysis revealed that HLA-DQB1*05:02 was significantly associated with NMOSD in the additive effect model and dominant effect model (p < 0.05). The proportion of haplotype "HLA-DQB1*05:02-DRB1*15:01" was significantly greater in the NMOSD patients than the controls, at 8.42% and 1.23%, respectively (p < 0.001, OR 7.39). The gene burden analysis demonstrated that loss-of-function mutations in NOP16 were more common in the NMOSD patients (11.84%) than the controls (5.71%; p < 0.001, OR 2.22). The IgG1-G390R variant was significantly more common in NMOSD, and the rate of the T allele was 0.605 in patients and 0.345 in the controls (p < 0.01, OR 2.92). The enrichment analysis indicated that most of the genetic factors were mainly correlated with nervous and immune processes. CONCLUSIONS: Human leukocyte antigen is highly correlated with NMOSD. NOP16 and IgG1-G390R play important roles in disease susceptibility.

2.
Sci Adv ; 7(4)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33523954

RESUMO

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

3.
J Int Med Res ; 49(1): 300060520982829, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33496629

RESUMO

Bullous pemphigoid (BP) is an autoimmune disease that requires immunosuppressive therapy. Systemic corticosteroids are considered the standard treatment for moderate-to-severe BP. Kaposi's sarcoma (KS) is a rare multifocal endothelial tumour that affects the skin, mucosa and viscera. As an angioproliferative disease of obscure aetiopathogenesis and histogenesis, KS is associated with human herpesvirus 8 (HHV-8). This current case report describes a rare occurrence of extensive cutaneous KS in a 60-year-old Chinese male patient after oral methylprednisolone treatment for BP with an emphasis on its pathological characterization. A total of more than 40 nodules were found on his trunk and lower limbs covering more than 20% of his body surface area. Immunohistochemical staining of biopsy samples from the lesion showed the patient was positive for HHV-8, CD31, CD34, XIIIa, ERG and Ki-67. The Epstein-Barr virus test showed the patient tested negative for immunoglobulin (Ig)A and IgM, but was positive for IgG. Immunosuppression associated with the treatment for BP may activate a latent HHV-8 infection and induce the development of KS.

4.
Oncogene ; 40(8): 1516-1530, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33452462

RESUMO

The basic leucine zipper ATF-like transcription factor 2 (BATF2) has been implicated in inflammatory responses and anti-tumour effects. Little, however, is known regarding its extracellular role in maintaining a non-supportive cancer microenvironment. Here, we show that BATF2 inhibits glioma growth and myeloid-derived suppressor cells (MDSCs) recruitment. Interestingly, extracellular vesicles (EVs) from BATF2-overexpressing glioma cell lines (BATF2-EVs) inhibited MDSCs chemotaxis in vitro. Moreover, BATF2 inhibited intracellular SDF-1α and contributes to decreased SDF-1α in EVs. In addition, BATF2 downregulation-induced MDSCs recruitment were reversed by blocking SDF-1α/CXCR4 signalling upon AMD3100 treatment. Specifically, detection of EVs in 24 pairs of gliomas and healthy donors at different stages revealed that the abundance of BATF2-positive EVs in plasma (BATF2+ plEVs) can distinguish stage III-IV glioma from stage I-II glioma and healthy donors. Taken together, our study identified novel regulatory functions of BATF2 in regulating MDSCs recruitment, providing a prognostic value in terms of the number of BATF2+ plEVs in glioma stage.

5.
J Hum Nutr Diet ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406287

RESUMO

BACKGROUND: Accurate estimation of food portion sizes remains an important challenge in dietary data collection. The present study aimed to develop a food atlas with adequate visual reference to improve the accuracy of dietary surveys in China. METHODS: A food atlas for dietary surveys in China was developed using three visual reference systems, namely, regularly placed food portions, the two-dimensional background coordinates and common objects known in daily life. The atlas was validated by estimating a meal before and after using the food atlas, and differences in weight estimation were compared using a paired t-test. In total, 50 college students participated in the study. RESULTS: After determination of food varieties; design of the food display; purchase, processing, cooking and weighing of food; photographing food; post-image processing and data processing, a total of 799 pictures of 303 types of food and two types of tableware were produced. The mean value of food weight estimated with the atlas was closer to the actual weight, and the variation range of these values was smaller and more stable than that estimated without the atlas. The differences estimated before and after using the atlas for all foods were significant (P < 0.05). Comparing the differences in weight before using the atlas, the error ranges of food samples were reduced. CONCLUSIONS: A food atlas has been developed for a retrospective dietary survey in China, which can be used to enable a better understanding of nutritional adequacy in the Chinese population.

6.
IEEE Trans Cybern ; PP2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33502993

RESUMO

Wavelet transform is being widely used in classical image processing. One-dimension quantum wavelet transforms (QWTs) have been proposed. Generalizations of the 1-D QWT into multilevel and multidimension have been investigated but restricted to the quantum wavelet packet transform (QWPTs), which is the direct product of 1-D QWPTs, and there is no transform between the packets in different dimensions. A 2-D QWT is vital for image processing. We construct the multilevel 2-D QWT's general theory. Explicitly, we built multilevel 2-D Haar QWT and the multilevel Daubechies D4 QWT, respectively. We have given the complete quantum circuits for these wavelet transforms, using both noniterative and iterative methods. Compared to the 1-D QWT and wavelet packet transform, the multilevel 2-D QWT involves the entanglement between components in different degrees. Complexity analysis reveals that the proposed transforms offer exponential speedup over their classical counterparts. Also, the proposed wavelet transforms are used to realize quantum image compression. Simulation results demonstrate that the proposed wavelet transforms are significant and obtain the same results as their classical counterparts with an exponential speedup.

7.
J Clin Neurosci ; 83: 108-111, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33317883

RESUMO

BACKGROUND: Serum neurofilament light chain (sNfL) is a promising biomarker for neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS), but there is limited validation data in specific ethnic and disease groups. OBJECTIVE: To investigate the levels of sNfL in a cohort of Chinese patients with NMOSD and compare sNfL levels in patients with different disease courses and treatments. METHODS: We analysed sNfL levels in 153 Chinese patients with NMOSD (n = 51) and MS (n = 102) using single-molecule array (Simoa) technology. The sNfL levels were compared with those of 71 healthy controls from two centres in southern China. For each disease, we assessed correlations between sNfL and disease phases and treatments. RESULTS: Higher levels of sNfL were found in the patients with NMOSD [17.97 (10.55-27.94) pg/mL] and MS [15.83 (8.92-25.67) pg/mL] compared to healthy controls [10.09 (7.19-13.29) pg/mL, p < 0.001]. No significant differences were found between the AQP4-IgG-positive NMOSD group and OCB-positive MS group. CONCLUSIONS: sNfL measured by Simoa technology is a potential candidate blood biomarker for the diagnosis and disease monitoring of NMOSD in Chinese patients, warranting further prospective and multicentre studies.

8.
Sci Total Environ ; 754: 141999, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254870

RESUMO

N-doped carbon materials have been proven to be effective catalysts for activating peroxymonosulfate (PMS). Marine algae biomass is rich in nitrogenous substances , which can reduce the cost of N-doping process and can obtain excellent N-doped catalysts cheaply and easily. In this study, kelp biomass was selected to prepare N-doped kelp biochar (KB) materials. The high defect degree, high specific surface area, and participation of graphite N make KB have excellent catalytic degradation ability. The KB degraded 40 mg/L ofloxacin (OFL) close to 100% within 60 min, applied with PMS. Through quenching experiments and electron paramagnetic resonance spectroscopy, the degradation process dominated by non-radical pathways was determined. At the same time, O2·- and 1O2 were closely related, and a significant impact of quenching O2·- on the reaction was observed. The non-radical approach made the system excellent performance over a wide pH range and in the presence of multiple anions. The experiments of reusability confirmed the stability of the material. Its catalytic performance was restored after low-temperature pyrolysis. This research supports the use of endogenous nitrogen in biomass. It provides more options for advanced oxidation process application and marine resource development.


Assuntos
Kelp , Carvão Vegetal , Ofloxacino , Peróxidos
9.
Reprod Biol Endocrinol ; 18(1): 121, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287836

RESUMO

BACKGROUND: It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS). METHODS: Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH, n = 30) or without GH treatment (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay. RESULTS: Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (P < 0.05). The mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly decreased, whereas Bcl-2 was increased in GCs of the PCOS-GH group than those in the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were decreased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were increased in GCs of the PCOS-GH group, compared with those in the PCOS-C group (P < 0.05). CONCLUSION: OS induced apoptosis and downregulated the PI3K/Akt signaling pathway in patients with PCOS. GH could alleviate apoptosis and activate the PI3K/Akt signaling pathway. CLINICAL TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry. ChiCTR1800019437 . Prospectively registered on October 20, 2018.

10.
Carcinogenesis ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269791

RESUMO

Macrophages are a double-edged sword with potential cancer-promoting and anti-cancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus (GEO) database by The CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increased in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma were significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient's lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage CM inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC.

11.
Aging (Albany NY) ; 13(2): 2049-2072, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323552

RESUMO

The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 (FGL2), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of FGL2 correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.

12.
Adv Mater ; : e2004070, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225525

RESUMO

Since the first experimental discovery of graphene 16 years ago, many other 2D layered nanomaterials have been reported. However, the majority of 2D nanostructures suffer from relatively complicated fabrication processes that have bottlenecked their development and their uptake by industry for practical applications. Here, the recent progress in sensing, photonic, and (opto-)electronic applications of PtSe2 , a 2D layered material that is likely to be used in industries benefiting from its high air-stability and semiconductor-technology-compatible fabrication methods, is reviewed. The advantages and disadvantages of a range of synthesis methods for PtSe2 are initially compared, followed by a discussion of its outstanding properties, and industrial and commercial advantages. Research focused on the broadband nonlinear photonic properties of PtSe2 , as well as reports of its use as a saturable absorber in ultrafast lasers, are then reviewed. Additionally, the advances that have been achieved in a range of PtSe2 -based field-effect transistors, photodetectors, and sensors are summarized. Finally, a conclusion on these results along with the outlook for the future is presented.

13.
ACS Appl Mater Interfaces ; 12(47): 52845-52856, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33170619

RESUMO

Conversion-type batteries with electrode materials partially dissolved in a liquid electrolyte exhibit high specific capacity and excellent redox kinetics, but currently poor stability due to the shuttle effect. Using a solid-electrolyte separator to block the mass exchange between the cathode and the anode can eliminate the shuttle effect. A stable interface between the solid-electrolyte separator and the liquid electrolyte is essential for the battery performance. Here, we demonstrate that a stable interface with low interfacial resistance and limited side reactions can be formed between the sulfide solid-electrolyte ß-Li3PS4 and the widely used ether-based liquid electrolytes, under both reduction and oxidation conditions, due to the rapid formation of an effective protective layer of ether-solvated Li3PS4 at the sulfide/liquid electrolyte interface. This discovery has inspired the design of a ß-Li3PS4-coated solid-electrolyte Li7P3S11 separator with a simultaneously high ion-conduction ability and good interfacial stability with the liquid electrolyte, so that hybrid lithium-sulfur (Li-S) batteries with this composite separator conserve a high discharge capacity of 1047 mA h g-1 and a high second discharge plateau of 2.06 V after 150 cycles.

14.
Reprod Sci ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33171515

RESUMO

GALNT2 is a GalNAc transferase that regulates insulin signaling, lipogenesis, and serum lipid fractions. The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of polycystic ovary syndrome (PCOS) and related traits. The two SNPs were genotyped in 616 PCOS patients and 482 control subjects. Genetic associations with related traits were also analyzed. The genotype distributions of the two SNPs in PCOS patients were similar to those of normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables. In the PCOS group, subjects with genotype AA at the rs4846914 SNP exhibited an increased fasting serum insulin and homeostasis model insulin resistance (HOMA-IR) index compared with that of corresponding GG or GA genotype carriers (all P < 0.05). When PCOS patients were further separated into obese and non-obese subgroups, the genotype-related effects on insulin and HOMA-IR were more obvious, and variations in BMI and FSH levels were exclusively observed in obese PCOS subjects (all P < 0.05). In addition, fasting plasma glucose levels were affected by the genotypes of the rs2144300 SNP in normal control women (P < 0.05). rs4846914 and rs2144300 polymorphisms in the GALNT2 gene are associated with insulin and HOMA-IR, BMI, and FSH levels in obese PCOS patients and glucose levels in normal control women, respectively, but not with PCOS. GALNT2 rs4846914 AA carrier status may be associated with insulin resistance and related traits in obese patients.

15.
Mol Cancer Ther ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177154

RESUMO

Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen's anti-tumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecological and non-gynecological adverse events thus the development of safer estrogenic agents remains a clinical priority. Here, we study synthetic selective estrogen mimics (SEMs) BMI-135 and TTC-352, and the naturally-occurring estrogen estetrol (E4), which are proposed as safer estrogenic agents compared to 17ß-estradiol (E2), for the treatment of endocrine-resistant BC. TTC-352 and E4 are being evaluated in BC clinical trials. Cell viability assays, real-time polymerase chain reaction, immunoblotting, ERE DNA pull downs, Mass spectrometry, X-ray crystallography, docking and molecular dynamic simulations, live cell imaging, and annexin V staining were conducted in 11 biologically-different BC models. Results were compared with the potent full agonist E2, less potent full agonist E4, the benchmark partial agonist triphenylethylene bisphenol (BPTPE), and antagonists 4-hydroxytamoxifen and endoxifen. We report ERα's regulation and coregulators' binding profiles with SEMs and E4. We describe TTC-352's pharmacology as a weak full agonist and anti-tumor molecular mechanisms. This study highlights TTC-352's benzothiophene scaffold that yields an H-bond with Glu353, which allows Asp351-to-helix 12 (H12) interaction; sealing ERα's ligand binding domain, recruiting E2-enriched coactivators, and triggering rapid ERα-induced unfolded protein response (UPR) and apoptosis, as the basis of its anti-cancer properties. BPTPE's phenolic OH yields an H-Bond with Thr347, which disrupts Asp351-to-H12 interaction; delaying UPR and apoptosis, and increasing clonal evolution risk.

16.
Electromagn Biol Med ; : 1-16, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179558

RESUMO

Physiological electric fields (EFs), as one of the environmental cues influencing both normal and tumor cells, have profound effects on tumor cell malignancy potential. The cellular responses to EFs by choriocarcinoma cells and their underlying mechanisms are unknown. In this study, the migration/motility, cell cycle progression and proliferation of choriocarcinoma cells in electric field culture showed that choriocarcinoma cells migrated cathodally in an applied EF, and EF stimulation influenced cell cycle progression through G2/M arrest and therefore induced a reduction in cellular proliferation. The transcriptome of choriocarcinoma cells subjected to EF stimulation (150 mV/mm) was analyzed using RNA sequencing (RNA-Seq), and the results were verified by reverse transcription quantitative polymerase chain reaction. A Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that ErbB and HIF-1 signaling pathways that are involved in cell migration/motility, cell cycle progression and proliferation were significantly altered in cells treated with an EF of 150 mV/mm compared with control cells, and in addition, the downstream pathways of these signaling pathways such as AKT and P42/P44 MAPK (ERK1/2) showed primary activation by Western blotting. This study's results suggest that an applied EF is an effective cue in regulating cellular phenotypes of choriocarcinoma cells and that transcriptional analysis contributes to the understanding of the mechanism of EF-guided cell functions.

17.
Explor Target Antitumor Ther ; 1: 355-371, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33210098

RESUMO

Aim: Tamoxifen (TAM) resistance remains a clinical issue in breast cancer. The authors previously reported that 15-hydroxyprostaglandin dehydrogenase (HPGD) was significantly downregulated in tamoxifen-resistant (TAMr) breast cancer cell lines. Here, the authors investigated the relationship between HPGD expression, TAM resistance and prediction of outcome in breast cancer. Methods: HPGD overexpression and silencing studies were performed in isogenic TAMr and parental human breast cancer cell lines to establish the impact of HPGD expression on TAM resistance. HPGD expression and clinical outcome relationships were explored using immunohistochemistry and in silico analysis. Results: Restoration of HPGD expression and activity sensitised TAMr MCF-7 cells to TAM and 17ß-oestradiol, whilst HPGD silencing in parental MCF-7 cells reduced TAM sensitivity. TAMr cells released more prostaglandin E2 (PGE2) than controls, which was reduced in TAMr cells stably transfected with HPGD. Exogenous PGE2 signalled through the EP4 receptor to reduce breast cancer cell sensitivity to TAM. Decreased HPGD expression was associated with decreased overall survival in ERα-positive breast cancer patients. Conclusions: HPGD downregulation in breast cancer is associated with reduced response to TAM therapy via PGE2-EP4 signalling and decreases patient survival. The data offer a potential target to develop combination therapies that may overcome acquired tamoxifen resistance.

18.
Infect Dis Poverty ; 9(1): 161, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239109

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

19.
J Cell Mol Med ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33124763

RESUMO

Cav 1.3 can affect the classical osteoclast differentiation pathway through calcium signalling pathway. Here, we performed cell transfection, real-time fluorescence quantitative PCR (qPCR), flow cytometry, SA-ß-Gal staining, Alizarin Red S staining, ALP activity test, immunofluorescence, Western blot and cell viability assay to analyse cell viability, cell cycle, osteogenesis differentiation and autophagy activities in vitro. Meanwhile, GST-pull down and CHIP experiments were conducted to explore the influence of Cav 1.3 and Sprouty-related EVH1 domain 2 (Spred 2) on bone marrow-derived mesenchymal stem cells (BMSCs). The results showed that OS lead to the decreased of bone mineral density and differentiation ability of BMSCs in rats. Cav 1.3 was up-regulated in OS rats. Overexpression of Cav 1.3 inhibited the activity of BMSCs, the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), as well as promoted the cell cycle arrest and senescence. Furthermore, the negative correlation between Cav 1.3 and Spred 2 was found through GST-pull down and CHIP. Overexpression of Spred 2 increased the expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 of BMSCs, which ultimately promoted the cell activity of BMSCs and ALP, RUNX2, OCN expression. In conclusion, Cav 1.3 negatively regulates Spred 2-mediated autophagy and cell senescence, and damages the activity and osteogenic differentiation of BMSCs in OS rats.

20.
Sci Rep ; 10(1): 18769, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127971

RESUMO

Oxidative stress (OS) is associated with poor oocyte quality and in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with polycystic ovary syndrome (PCOS). Growth hormone (GH) can function to reduce OS in some types of cells. Therefore, this prospective randomized study investigated whether GH can significantly improve OS and oocyte quality in women with PCOS. This study enrolled 109 and 50 patients with and without PCOS (controls), respectively. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-T) or not (PCOS-C). The primary outcome included markers of OS in serum and FF, and secondary outcomes were mitochondrial function in granulosa cells (GCs) and IVF-ET outcomes. The PCOS groups showed higher basal serum total oxidant status (TOS) and OS index (OSI) levels. The follicle fluid (FF) TOS and OSI and GC apoptosis rate were significantly higher, whereas the GC mitochondrial membrane potential (MMP) was significantly lower in the PCOS-C group than in the PCOS-T and non-PCOS control groups (P < 0.05). Significantly more oocytes were fertilised and cleavage stage embryos were produced in the PCOS-T group than in the PCOS-C group (P < 0.05). GH also improved the rates of implantation and clinical pregnancy, but not significantly (P > 0.05). This study showed that GH alleviated the TOS and OSI level in FF and improved GC mitochondrial dysfunction and oocyte quality in patients with PCOS.Clinical Trial Registration Number: This project was prospectively registered on the Chinese Clinical Trial Registry on October 20, 2018. (ChiCTR1800019437) ( https://www.chictr.org.cn/edit.aspx?pid=28663&htm=4 ).

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