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1.
Nanomaterials (Basel) ; 11(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803187

RESUMO

Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system; however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation.

2.
Int J Nanomedicine ; 16: 2477-2486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824586

RESUMO

Purpose: Sensitive and selective point-of-care biosensor is an urgent pursuit of serological antibody detection to control parasite pathogen. For specific, quantitative and on-site screening of Trichinella spiralis infection in livestock, a quantum dot nanobead-monoclonal antibody (QB-mAb) probe-based immunochromatographic assay (ICA) was developed by introducing a competitive sandwich strategy (QB-CICA). Methods: In the QB-CICA, QB-mAb probes competed with serum antibody for a particular epitope, followed by immunocomplexes binding to capture antibody on the test line. With the accumulation of target antibody, captured probes served as signal elements for fluorescent readout in a "turn off" mode, along with the fluorescence gradually weakened. The sensitivity and standard calibration curve of the QB-CICA were quantified using swine sera as negative control (n = 200) and artificial infected swine sera (n = 80) compared with a commercial ELISA kit. Besides, Trichinella spiralis-antibody targeting test ability of the QB-CICA, instead of other parasites or viruses antibodies (n = 10), was evaluated. Results: The QB-CICA exhibited a good linear range, a low detection limit of 189.92 ng mL-1 and 100% selectivity that was higher than commercial ELISA kit (90%), as well as the same serological positive rate (100%) with commercial ELISA kit in different infection dose models. Conclusion: Taking advantage of its simplicity, short response time (25 min), sensitivity and specificity, the proposed QB-CICA has potential applications for parasite-related antibody monitoring in food safety and clinical diagnosis fields.

3.
Cell Tissue Bank ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837877

RESUMO

Vascular network reconstruction plays a pivotal role in the axonal regeneration and nerve function recovery after peripheral nerve injury. Increasing evidence indicates that Schwann cells (SCs) can promote nerve function repair, and the beneficial effects attributed to SCs therapy may exert their therapeutic effects through paracrine mechanisms. Recently, the previous research of our group demonstrated the promising neuroregenerative capacity of Schwann-like cells (SCLCs) derived from differentiated human embryonic stem cell-derived neural stem cells (hESC-NSCs) in vitro. Herein, the effects of SC-like cell conditioned medium (SCLC-CM) on angiogenesis and nerve regeneration were further explored. The assays were performed to show the pro-angiogenic effects of SCLC-CM, such as promoted endothelial cell proliferation, migration and tube formation in vitro. In addition, Sprague-Dawley rats were treated with SCLC-CM after sciatic nerve crush injury, SCLC-CM was conducive for the recovery of sciatic nerve function, which was mainly manifested in the SFI increase, the wet weight ratio of gastrocnemius muscle, as well as the number and thickness of myelin. The SCLC-CM treatment reduced the Evans blue leakage and increased the expression of CD34 microvessels. Furthermore, SCLC-CM upregulated the expressions of p-Akt and p-mTOR in endothelial cells. In conclusion, SCLC-CM promotes angiogenesis and nerve regeneration, it is expected to become a new treatment strategy for peripheral nerve injury.

4.
Carbohydr Polym ; 261: 117869, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766356

RESUMO

Osteoarthritis (OA) is an age-related joint disorder and one of the leading causes of physical disability. In this study, we designed and synthesized a new polysaccharide complex, carboxymethyl chitosan strontium (CMCS-Sr), which is believed to have positive effects on relieving OA. The synthesized CMCS-Sr was structurally verified by SEM, EDS, FTIR, etc. The therapeutic effects of CMCS-Sr were evaluated using various biological experiments. The cell viability and apoptosis results reveal that CMCS-Sr can significantly promote the proliferation and suppress OA chondrocytes apoptosis in vitro. The immunofluorescence staining results suggest that CMCS-Sr facilitates the promotion of the secretion of Type II collagen (Col-II). The transcriptomic results support the observed positive effects of CMCS-Sr on inhibiting chondrocytes apoptosis and alleviating inflammatory reactions. Moreover, animal study demonstrates that CMCS-Sr effectively reduced articular cartilage damage and subchondral bone degradation. Therefore, we propose the use of CMCS-Sr as a promising candidate for relieving OA.

5.
Commun Biol ; 4(1): 402, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767359

RESUMO

Osteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.

6.
J Biomed Nanotechnol ; 17(2): 291-302, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33785099

RESUMO

Schwann cells promote axonal regeneration following peripheral nerve injury. However, in terms of clinical treatment, the therapeutic effects of Schwann cells are limited by their source. The transmission of microvesicles from neuroglia cells to axons is a novel communication mechanism in axon regeneration.To evaluate the effect of microvesicles released from Schwann-like cells on axonal regeneration, neural stem cells derived from human embryonic stem cells differentiated into Schwann-like cells, which presented a typical morphology and characteristics similar to those of schwann cells. The glial markers like MBP, P0, P75NTR, PMP-22, GFAP, HNK-1 and S100 were upregulated, whereas the neural stem markers like NESTIN, SOX1 and SOX2 were significantly downregulated in schwann-like cells. Microvesicles enhanced axonal growth in dorsal root ganglia neurons and regulated GAP43 expression in neuron-like cells (N2A and PC12) through the PTEN/PI3 K/Akt signaling pathway. A 5 mm section of sciatic nerve was transected in Sprague-Dawley rats. With microvesicles transplantation, regenerative nerves were evaluated after 6 weeks. Microvesicles increased sciatic function index scores, delayed gastrocnemius muscle atrophy and elevated ßIII-tubulin-labeled axons in vivo. Schwann-like cells serve as a convenient source and promote axonal growth by secreting microvesicles, which may potentially be used as bioengineering materials for nerve tissue repair.


Assuntos
Axônios , Regeneração Nervosa , Animais , Materiais Biocompatíveis , Ratos , Ratos Sprague-Dawley , Células de Schwann , Nervo Isquiático
7.
Neurosurg Rev ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33738637

RESUMO

Intraoperative internal carotid artery injury is one of the most daunting complications in endoscopic skull base surgery. This paper proposed a novel technique to manage ICA injury after proximal and distal controls. The appropriate block sites together with the proximal and distal controls of ICA were demonstrated in six injected cadaveric specimens. The surgical outcomes of five patients with intraoperative ICA injury and managed with this concept were retrospectively reviewed. Five block sites for vascular control could be identified in all six specimens, including (1) distal to the distal dural ring, (2) proximal to the proximal dural ring, (3) anterior genu of the parasellar ICA, (4) the upper third of the paraclival ICA, and (5) just above the foramen lacerum. Both proximal and distal controls of ICA were achieved by using the block sites in combination. Gross tumor resection was achieved in all five cases after the intraoperative ICA injury was successfully managed. Three coping techniques were used, including direct coagulation to seal (three cases), endoscopic suture (one case), and coagulation to sacrifice (one case). Focal brainstem infarction occurred in one case, one patient died of intracranial infection, and the other three cases had no sequelae. No pseudoaneurysm occurred in all patients. Except the sacrificed ICA, the other ICA was intact during follow-up. It is technically feasible to manage ICA injuries after proximal and distal controls during EEA surgeries. The surgical outcomes from our case series supported the use of this novel technique.

8.
ACS Biomater Sci Eng ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691399

RESUMO

Microbial infection and the limitation of tissue regeneration are main obstacles to chronic wound healing. Herein, a biofunctional hydrogel is prepared to simultaneously kill bacteria efficiently and promote would healing. First, a rose bengal/polypyrrole hybrid poly(vinyl alcohol) hydrogel (RB/PPy PVA HD) is synthesized and its antibacterial property is investigated under coirradiation of 550 nm visible light and 808 near-infrared light. The hydrogel exhibits excellent antibacterial activity within 10 min below 45 °C in vitro due to the synergistic effect of photothermal and photodynamic antibacterial therapy. Next, the recombined human epidermal growth factor (rhEGF) is physically absorbed on the surface of the porous hydrogel to form a RB/PPy/rhEGF hybrid PVA HD (rhEGF/RB/PPy PVA HD). The introduction of rhEGF enables the hydrogel to promote fibroblast proliferation and collagen secretion. Furthermore, the in vivo results indicate that the rhEGF/RB/PPy PVA HD can control infection effectively and promote wound healing significantly.

9.
Sci Rep ; 11(1): 5246, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664411

RESUMO

Glutamine:fructose-6-phosphate aminotransferase (GFAT) and phosphofructokinase (PFK) are enzymes related to chitin metabolism. RNA interference (RNAi) technology was used to explore the role of these two enzyme genes in chitin metabolism. In this study, we found that GFAT and PFK were highly expressed in the wing bud of Nilaparvata lugens and were increased significantly during molting. RNAi of GFAT and PFK both caused severe malformation rates and mortality rates in N. lugens. GFAT inhibition also downregulated GFAT, GNPNA, PGM1, PGM2, UAP, CHS1, CHS1a, CHS1b, Cht1-10, and ENGase. PFK inhibition significantly downregulated GFAT; upregulated GNPNA, PGM2, UAP, Cht2-4, Cht6-7 at 48 h and then downregulated them at 72 h; upregulated Cht5, Cht8, Cht10, and ENGase; downregulated Cht9 at 48 h and then upregulated it at 72 h; and upregulated CHS1, CHS1a, and CHS1b. In conclusion, GFAT and PFK regulated chitin degradation and remodeling by regulating the expression of genes related to the chitin metabolism and exert opposite effects on these genes. These results may be beneficial to develop new chitin synthesis inhibitors for pest control.

10.
Front Immunol ; 12: 602492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717085

RESUMO

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96-CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT-NK cells, while CD96+CD226- cells expanded. Reduced CD96-CD226+ cells and elevated CD96+CD226- cells among NK cells especially TIGIT-NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A-NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C-NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A-NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT-NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT-NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT-NK cells, except for TNF-α-CD107a+IFN-γ-NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

11.
Iran J Parasitol ; 16(1): 122-135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33786054

RESUMO

Background: Trichinellosis is a serious food-borne parasitic zoonosis, thus finding high quality antigens is the key to serodiagnosis of trichinosis. This article reports the characterization and sensitivity of four recombinant proteins expressed by four genes (Wn10, Zh68, T668, and Wm5) from different developmental stages of Trichinella spiralis for the diagnosis of trichinellosis in mice. Methods: This study was conducted in Jilin University and National Institute of Parasitic Diseases of Chinese Center for Disease Control and Prevention in 2017-2018. The structures and functions of the proteins encoded by four genes were predicted by bioinformatics analysis. The four genes were cloned and expressed, and the recombinant proteins were purified. Anti-Trichinella IgM and IgG antibodies in the sera of mice infected with T. spiralis from 1-45 d post-infection (dpi) were evaluated by ELISA. Results: The optimal antigen epitopes of four proteins (P1, P2, P3, and P4) encoded by the four genes from T- and B-cells were predicted, and four purified recombinant proteins (r-P1, r-P2, r-P3, and r-P4) were successfully produced. For IgM, the antibody levels detected by the four recombinant antigens were approximately equal to the cut-off value. Anti-Trichinella IgG antibodies were first detected by r-P1 at 8 dpi, followed by r-P2, r-P3, and r-P4 at 10 dpi, 14 dpi, and 16 dpi, respectively, and the antibody levels remained high until 45 dpi. Conclusion: The recombinant antigens r-P1, r-P2, r-P3, and r-P4 could be antigens that react with antibodies, they showed high sensitivity in the detection of anti-Trichinella IgG antibodies in mice. Among these proteins, r-P1 may be a candidate antigen for the detection of anti-Trichinella IgG antibodies in the early infection phase and exhibited the best sensitivity among the antigens.

12.
Front Immunol ; 12: 627226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732250

RESUMO

Background: Vitamin D deficiency is a well-described preventable cause of many cancers; the association of vitamin D use with the development of head and neck cancer (HNC) is not clear. We aim to conduct a systematic review of the studies assessing the relation between vitamin D exposure and the prevention and prognosis of the HNC using meta-analysis. Methods: PubMed, EMBASE, Cochrane Library, Web of Science up to 1 January 2021, and reference lists of related studies were searched. We extracted observational studies reporting the association between vitamin D (vitamin D receptor gene polymorphisms, 25-hydroxyvitamin D concentrations, and vitamin D intake) and the outcomes of interest (HNC incidence and HNC mortality) in HNC patients aged 18 or older. Fixed effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs) by RevMan (version 5.3). Results: Sixteen studies with a total of 81,908 participants were enrolled in our meta-analysis. Based on the pooled genomic analysis, comparing with participants with the genotypes of Ff + FF or FF, the pooled odds ratio (OR) of participants with the genotype of ff was 0.77 (95% CI: 0.61 to 0.97) and 0.75 (0.58 to 0.97), respectively. A similar trend was noted when comparing tt with Tt + TT or TT, in which OR (95% CI) was 0.70 (0.55 to 0.90) and 0.72 (0.55 to 0.95). No significant association was identified between BsmI polymorphism and HNC. Furthermore, the OR of HNC incidence was 0.77 (0.65 to 0.92) for participants with vitamin D intake over the ones with a regular diet. High concentrations of circulated 25-hydroxyvitamin D (25-OHD) significantly decreased by 32% of HNC incidence (OR (95% CI): 0.68 (0.59 to 0.78)) and increased HNC survival (pooled hazard ratio 1.13, 1.05 to 1.22) during a 4-5 years follow-up. High concentrations of circulating 25-OHD in patients with HNC led to a decreased risk of mortality to 0.75 (0.60 to 0.94) as the follow-up extends to 8-12 years. Conclusions: Elevated activities of vitamin D by diet intake, genomic polymorphisms, or circulated 25-OHD may protect people from HNC and improve the prognosis of patients with HNC. Systematic Review Registration: PROSPERO, identifier CRD42020176002 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=176002).

13.
Int J Biol Macromol ; 181: 452-461, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33775764

RESUMO

Bone regeneration and repair has become one of the major clinical challenges worldwide and it involves multiple processes including inflammation, angiogenesis and osteogenesis. In this study, we synthesized strontium Laminarin polysaccharide (LP-Sr), a novel polysaccharide-metal complex that should have therapeutic effects on modulating osteogenesis and angiogenesis. The structure and composition of the as-fabricated LP-Sr were analyzed by EDS, XRD, FITR, 1H NMR, HPLC, etc. The results indicate that we successfully synthesized this novel polysaccharide complex. Moreover, we evaluated the biomedical potential of this complex in promoting osteogenesis and angiogenesis by cell proliferation assay, ALP staining, immunofluorescent staining of CD31 and reverse transcription polymerase chain reaction (RT-PCR). The biological experiment results show that LP-Sr can effectively promote proliferation and increase the expression of VEGF and EGFL6 in HUVECs and significantly up-regulate the expression of Col1α1 and OCN in MC3T3-E1. Besides, it is suggested that LP-Sr has positive effects on the suppression of pro-inflammatory factor IL6 in both HUVECs and MC3T3-E1. Moreover, the osteogenic and angiogenic markers, i.e. alkaline phosphatase (ALP) and CD31, exhibited high expression in LP-Sr group. Hence, we believe that LP-Sr should be a promising and novel polysaccharide complex in modulating osteogenesis-angiogenesis for bone regeneration.

14.
J Appl Clin Med Phys ; 22(3): 55-62, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33527712

RESUMO

PURPOSE AND BACKGROUND: The magnetic resonance (MR)-only radiotherapy workflow is urged by the increasing use of MR image for the identification and delineation of tumors, while a fast generation of synthetic computer tomography (sCT) image from MR image for dose calculation remains one of the key challenges to the workflow. This study aimed to develop a neural network to generate the sCT in brain site and evaluate the dosimetry accuracy. MATERIALS AND METHODS: A generative adversarial network (GAN) was developed to translate T1-weighted MRI to sCT. First, the "U-net" shaped encoder-decoder network with some image translation-specific modifications was trained to generate sCT, then the discriminator network was adversarially trained to distinguish between synthetic and real CT images. We enrolled 37 brain cancer patients acquiring both CT and MRI for treatment position simulation. Twenty-seven pairs of 2D T1-weighted MR images and rigidly registered CT image were used to train the GAN model, and the remaining 10 pairs were used to evaluate the model performance through the metric of mean absolute error. Furthermore, the clinical Volume Modulated Arc Therapy plan was calculated on both sCT and real CT, followed by gamma analysis and comparison of dose-volume histogram. RESULTS: On average, only 15 s were needed to generate one sCT from one T1-weighted MRI. The mean absolute error between synthetic and real CT was 60.52 ± 13.32 Housefield Unit over 5-fold cross validation. For dose distribution on sCT and CT, the average pass rates of gamma analysis using the 3%/3 mm and 2%/2 mm criteria were 99.76% and 97.25% over testing patients, respectively. For parameters of dose-volume histogram for both target and organs at risk, no significant differences were found between both plans. CONCLUSION: The GAN model can generate synthetic CT from one single MRI sequence within seconds, and a state-of-art accuracy of CT number and dosimetry was achieved.

15.
Chemosphere ; 271: 129830, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33556630

RESUMO

In this work, we have constructed a novel graphitic carbon nitride/multiwall carbon nanotube (GCN/CNT) doped Ti/PbO2 as anode for highly effective degradation of acetaminophen (ACE) wastewater. The ACE removal efficiency of 83.2% and chemical oxygen demand removal efficiency of 76.3% are achieved under the optimal condition of temperature 25 °C, initial pH 7, current density 15 mA cm-2 and Na2SO4 concentration 6.0 g L-1. The excellent electrocatalytic activity of Ti/PbO2-GCN-CNT anode for ACE oxidation is ascribed to the effective suppression of oxygen evolution and the enhanced electron transfer after introducing GCN and CNT. Furthermore, Ti/PbO2-GCN-CNT electrode displays excellent stability and reusability. ACE degradation is accomplished by direct oxidation and indirect oxidation, and ∙OH radical plays primary role in the indirect oxidation of ACE wastewater. The intermediates of ACE degradation are detailly investigated using LC-MS analysis and a possible degradation mechanism is proposed.


Assuntos
Nanotubos de Carbono , Poluentes Químicos da Água , Acetaminofen , Eletrodos , Grafite , Compostos de Nitrogênio , Oxirredução , Óxidos , Titânio , Poluentes Químicos da Água/análise
16.
J Neuroimmunol ; 353: 577493, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571816

RESUMO

Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514 pg/ml versus median 317 pg/ml, p = 0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5 ng/ml versus median 7.6 ng/ml, p = 0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p = 0.038) and plasma HIV detectability (p = 0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.

17.
Laryngoscope ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33592124

RESUMO

OBJECTIVE/HYPOTHESIS: Hepatitis C virus (HCV) was reported to associate with head and neck squamous cell carcinoma (HNSCC) in many studies. However, its correlation with prognosis of non-human papillomavirus (HPV) associated HNSCC remains unknown. Here, we sought to investigate clinical significance of HCV RNA transcript in non-HPV associated HNSCC by analyzing corresponding RNA-seq data. STUDY DESIGN: A retrospective cohort study. METHODS: Four hundred and forty-eight non-HPV associated HNSCC patients with aligned RNA-seq and clinical follow-up data were included and divided into two groups: low-HCV and high-HCV. Means of continuous variables and proportions of categorical variables were compared using independent sample t-test and chi-square test, respectively. Survival data were compared using Cox regression analysis, Kaplan-Meier curves, and log-rank test. Expression of genome-wide mRNAs and abundance of immune cells were compared using volcano plot and cell signature estimated score analysis. RESULTS: HCV RNA transcript negatively correlates with pathologic (P = .028) and clinical-stage (P = .023), clinical N stage (P = .025), and nodal extracapsular spread (P = .042) and is an independent prognosis factor in non-HPV associated HNSCC (HR = 1.488; 95% CI: 1.004-2.206; P = .048). Elevated expression of HCV improved 5-year overall survival (43.6% vs. 53.2%; P = .035) in all non-HPV associated HNSCC patients, the same as in male (46.6% vs. 58.7%; P = .049), clinical M0 stage (42.8% vs. 52.9%; P = .036), white (42.9% vs. 55.9%; P = .010), and histologic grade 1 to 2 subgroups (42.1% vs. 57.2%; P = .043). The expression of several immune-related genes and abundance of some immune cells significantly changed with the increase of HCV RNA transcript, while HCV-related oncogenes and tumor suppressor gene did not. CONCLUSIONS: HCV RNA transcript is an independent favorable factor for prognosis of non-HPV associated HNSCC. LEVELS OF EVIDENCE: 4 Laryngoscope, 2021.

18.
Kaohsiung J Med Sci ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611829

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder. Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4+ T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.

19.
J Am Chem Soc ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567211

RESUMO

The growth of three-dimensional covalent organic frameworks (3D COFs) with new topologies is still considered as a great challenge due to limited availability of high-connectivity building units. Here we report the design and synthesis of 3D triptycene-based COFs, termed JUC-568 and JUC-569, following the deliberate symmetry-guided design principle. By combining a triangular prism (6-connected) node with a planar triangle (3-connected) or another triangular prism node, the targeted COFs adopt non-interpenetrated ceq or acs topology, respectively. Both materials show permanent porosity and impressive performance in the adsorption of CO2 (∼98 cm3/g at 273 K and 1 bar), CH4 (∼48 cm3/g at 273 K and 1 bar), and especially H2 (up to 274 cm3/g or 2.45 wt % at 77 K and 1 bar), which is highest among porous organic materials reported to date. This research thus provides a promising strategy for diversifying 3D COFs based on complex building blocks and promotes their potential applications in energy storage and environment-related fields.

20.
Acta Trop ; 217: 105852, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33548205

RESUMO

Clonorchiasis is a zoonotic disease that can result in chronic infection in humans. The causative agent, Clonorchis sinensis (C. sinensis), is believed to primarily induce a Th2 immune response in infected mice. However, few studies have profiled host immune responses to C. sinensis infection during the juvenile phase. In the present study, the dynamics of select cellular responses and cytokine expression profiles during juvenile C. sinensis infection were investigated. The flow cytometry results showed that the CD4+ T cells percentage was significantly decreased between 12 days post-infection (dpi) and 24 dpi in the peripheral blood, and the CD8+ T cells percentage was significantly elevated after 3 dpi. The ratio of CD4+/CD8+ T cells was also significantly decreased after 3 dpi. Furthermore, we observed that the proportion of CD14+ monocyte-macrophages in the peripheral blood was significantly increased between 1 dpi and 12 dpi and peaked at 6 dpi. The percentage of classically activated macrophages (M1) and alternatively activated macrophages (M2) in the liver was significantly increased between 18 dpi and 30 dpi. qRT-PCR results showed that the expression levels of iNOS in the liver were significantly elevated after 3 dpi, and Arg-1 expression was significantly increased beginning at 12 dpi. ELISA results showed that the serum levels of the Th1 cytokines IFN-γ and IL-2 peaked at 6 dpi and decreased thereafter. Furthermore, the Th2 cytokines IL-4 and IL-13 began to be expressed and peaked at 24 dpi and 30 dpi, respectively. In addition, the levels of the Treg cytokines IL-10 and TGF-ß1 were significantly increased beginning at 6 dpi until 30 dpi. In the liver homogenate, the expression of IFN-γ, IL-2, and IL-4 mainly occurred before 6 dpi. IL-13 expression was significantly increased at 30 dpi. IL-10 and TGF-ß1 levels were significantly increased at 12 dpi and 24 dpi, and expression peaked at 24 dpi and 30 dpi, respectively. This study provides a fundamental characterization for the future analysis of host-parasite interactions and immune responses in hosts infected with juvenile C. sinensis.

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