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1.
Life Sci Alliance ; 5(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34663690

RESUMO

Chd7 encodes an ATP-dependent chromatin remodeler which has been shown to target specific genomic loci and alter local transcription potentially by remodeling chromatin structure. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. We examined whether nuclear RNAs might contribute to its targeting and function and identified a preferential interaction between CHD7 and lncRNAs derived from HERVH loci in pluripotent stem cells. Knockdown of HERVH family lncRNAs using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH family RNAs led to the activation of multiple genes. CHD7 bound HERVH RNA with high affinity but low specificity and this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH lncRNAs act as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and the activation of numerous genes that might impact the differentiation process.

2.
J Neurosurg Spine ; : 1-14, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740175

RESUMO

OBJECTIVE: Previous studies have demonstrated the short-term radiographic and clinical benefits of circumferential minimally invasive surgery (cMIS) and hybrid (i.e., minimally invasive anterior or lateral interbody fusion with an open posterior approach) techniques to correct adult spinal deformity (ASD). However, it is not known if these benefits are maintained over longer periods of time. This study evaluated the 2- and 3-year outcomes of cMIS and hybrid correction of ASD. METHODS: A multicenter database was retrospectively reviewed for patients undergoing cMIS or hybrid surgery for ASD. Patients were ≥ 18 years of age and had one of the following: maximum coronal Cobb angle (CC) ≥ 20°, sagittal vertical axis (SVA) > 5 cm, pelvic incidence-lumbar lordosis mismatch (PI-LL) ≥ 10°, or pelvic tilt (PT) > 20°. Radiographic parameters were evaluated at the latest follow-up. Clinical outcomes were compared at 2- and 3-year time points and adjusted for age, preoperative CC, levels operated, levels with interbody fusion, presence of L5-S1 anterior lumbar interbody fusion, and upper and lower instrumented vertebral level. RESULTS: Overall, 197 (108 cMIS, 89 hybrid) patients were included with 187 (99 cMIS, 88 hybrid) and 111 (60 cMIS, 51 hybrid) patients evaluated at 2 and 3 years, respectively. The mean (± SD) follow-up duration for cMIS (39.0 ± 13.3 months, range 22-74 months) and hybrid correction (39.9 ± 16.8 months, range 22-94 months) were similar for both cohorts. Hybrid procedures corrected the CC greater than the cMIS technique (adjusted p = 0.022). There were no significant differences in postoperative SVA, PI-LL, PT, and sacral slope (SS). At 2 years, cMIS had lower Oswestry Disability Index (ODI) scores (adjusted p < 0.001), greater ODI change as a percentage of baseline (adjusted p = 0.006), less visual analog scale (VAS) back pain (adjusted p = 0.006), and greater VAS back pain change as a percentage of baseline (adjusted p = 0.001) compared to hybrid techniques. These differences were no longer significant at 3 years. At 3 years, but not 2 years, VAS leg pain was lower for cMIS compared to hybrid techniques (adjusted p = 0.032). Those undergoing cMIS had fewer overall complications compared to hybrid techniques (adjusted p = 0.006), but a higher odds of pseudarthrosis (adjusted p = 0.039). CONCLUSIONS: In this review of a multicenter database for patients undergoing cMIS and hybrid surgery for ASD, hybrid procedures were associated with a greater CC improvement compared to cMIS techniques. cMIS was associated with superior ODI and back pain at 2 years, but this difference was no longer evident at 3 years. However, cMIS was associated with superior leg pain at 3 years. There were fewer complications following cMIS, with the exception of pseudarthrosis.

3.
J Neurosurg Spine ; : 1-7, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740180

RESUMO

OBJECTIVE: Degenerative cervical myelopathy (DCM) results in significant morbidity. The duration of symptoms prior to surgical intervention may be associated with postoperative surgical outcomes and functional recovery. The authors' objective was to investigate whether delayed surgical treatment for DCM is associated with worsened postoperative outcomes. METHODS: Data from 1036 patients across 14 surgical centers in the Quality Outcomes Database were analyzed. Baseline demographic characteristics and findings of preoperative and postoperative symptom evaluations, including duration of symptoms, were assessed. Postoperative functional outcomes were measured using the Neck Disability Index (NDI) and modified Japanese Orthopaedic Association (mJOA) scale. Symptom duration was classified as either less than 12 months or 12 months or greater. Univariable and multivariable regression were used to evaluate for the associations between symptom duration and postoperative outcomes. RESULTS: In this study, 513 patients (49.5%) presented with symptom duration < 12 months, and 523 (50.5%) had symptoms for 12 months or longer. Patients with longer symptom duration had higher BMI and higher prevalence of anxiety and diabetes (all p < 0.05). Symptom duration ≥ 12 months was associated with higher average baseline NDI score (41 vs 36, p < 0.01). However, improvements in NDI scores from baseline were not significantly different between groups at 3 months (p = 0.77) or 12 months (p = 0.51). Likewise, the authors found no significant differences between groups in changes in mJOA scores from baseline to 3 months or 12 months (both p > 0.05). CONCLUSIONS: Surgical intervention resulted in improved mJOA and NDI scores at 3 months, and this improvement was sustained in both patients with short and longer initial symptom duration. Patients with DCM can still undergo successful surgical management despite delayed presentation.

4.
J Am Dent Assoc ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34756591

RESUMO

BACKGROUND: Studies have indicated the negative effects of temporomandibular disorders (TMDs) on oral health-related quality of life (OHRQoL). The authors investigated the OHRQoL of patients with acute and chronic TMD subtypes. METHODS: The authors recruited a total of 830 patients. They derived TMD diagnoses using the Diagnostic Criteria for TMDs protocol involving symptom history, physical examination, and diagnostic imaging as indicated. The authors categorized patients into acute (≤ 3 months) or chronic (> 3 months) pain-related TMD (PT), nonpainful intra-articular TMD (IT), and combined TMD (CT) groups. They also gathered sociodemographic information and assessed OHRQoL with the Oral Health Impact Profile (OHIP)-TMDs. The authors evaluated data using 2-way analysis of variance and Bonferroni test and multiple regression analysis. RESULTS: Patients in the chronic PT and CT subgroups had significantly higher mean global OHIP scores than their acute counterparts. The authors observed significant acute-chronic differences in OHIP-TMDs domain scores in 5 and 2 domains for the PT and CT groups, respectively. Patients in the acute IT group had significantly higher functional limitation scores than those in the chronic IT group. The ranking of mean global scores, in descending order was CT, PT, and IT for acute TMDs and PT, CT, and IT for chronic TMDs, with significant differences observed among the 3 TMD subtypes (P < .001). CONCLUSIONS: Both TMD chronicity and subtypes influenced OHRQoL. Painful TMDs (PT and CT) were associated with significantly poorer OHRQoL than nonpainful TMDs. TMD chronicity appeared to affect OHRQoL only for the painful TMD conditions. Future work on the impact of TMDs on OHRQoL should strive to stratify patients by TMD chronicity and subtypes. PRACTICAL IMPLICATIONS: TMD chronicity and subtypes influence the impact of TMDs on OHRQoL. Given that chronic painful TMDs impair quality of life, early biopsychosocial intervention of acute TMD pain is important for minimizing chronification and OHRQoL deterioration.

5.
Cancers (Basel) ; 13(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34771598

RESUMO

BACKGROUND: Whether perioperative packed red blood cell (pRBC) transfusion is associated with inferior long-term outcomes after stomach cancer surgery remains controversial. METHODS: This research used a retrospective cohort study. Patients with stage I~III stomach cancer undergoing tumor resection were collected at a tertiary medical center. Patient characteristics, surgical features and pathologic findings were gathered from an electronic medical chart review. The associations of perioperative pRBC transfusion with postoperative disease-free and overall survivals were evaluated using Cox regression analysis with an inverse probability of treatment weighting (IPTW). Restricted cubic spline functions were employed to characterize dose-response relationships between the amount of transfusion and cancer outcomes after surgery. RESULTS: Among the 569 patients, 160 (28.1%) received perioperative pRBC transfusion. Perioperative transfusion was associated with worse disease-free survival (IPTW adjusted HR: 1.42, 95% CI: 1.18-1.71, p < 0.001) and overall survival (IPTW adjusted HR: 1.27, 95% CI: 1.05-1.55, p = 0.014). A non-linear dose-response relationship was noted between the amount of transfusions and worse disease-free or overall survival. CONCLUSIONS: Perioperative pRBC transfusion was associated with worse disease-free and overall survival after stomach cancer surgery, and strategies aiming to minimize perioperative transfusion exposure should be further considered to reduce the potential risk.

6.
Int J Biol Sci ; 17(15): 4285-4304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803498

RESUMO

Circular RNAs (circRNAs) is a novel class of non-coding RNAs resulting from the non-canonical splicing of linear pre-mRNAs. However, the role of circRNAs in gastric cancer (GC) remains indistinct. This study aims to explore their potential modulation in GC and its prognostic value. We first screen for circRNA expression patterns in GC through GC and adjacent noncancerous tissues by microarray. Based on the bioinformatics analysis of the microarray data, we screened out a novel circRNA, circ-PTPDC1. Then we demonstrated that circ-PTPDC1 was up-regulated in GC cells, tissues, and serum. Its overexpression was positively correlated with age, invasion depth, advanced clinical stages, and worse survival in patients with GC. We further revealed that circ-PTPDC1 promotes the proliferation, migration, and invasion of GC cell lines via sponging miR-139-3p by regulating ELK1. Importantly, we identified that circ-PTPDC1 promotes tumor upgrowth and metabasis in vivo. Additionally, we established its prognostic prediction model based on the follow-up data of the patients. Our study revealed a novel regulatory mechanism and a comprehensive landscape of circ-PTPDC1 in GC, suggesting that circ-PTPDC1 has the potential to be a biomarker for early detection and prognostic prediction of GC.

7.
Int J Rheum Dis ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34821056

RESUMO

AIM: To investigate the associations of ultrasound and radiographic features of thumb-base osteoarthritis (OA) with thumb-base pain and hand function at baseline and 12 weeks. METHOD: Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb-base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self-reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12-week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors. RESULTS: A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound-detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks. CONCLUSION: This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb-base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb-base OA.

8.
Asian J Androl ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34782548

RESUMO

This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.

9.
Planta Med ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715693

RESUMO

Two new maytansinoids, N-methyltreflorine (1: ) and methyltrewiasine (2: ), were isolated from the dried fruits of Trewia nudiflora, together with three known congeners (3:  - 5: ). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1: and 2: was determined by X-ray crystallographic analysis. Compounds 1:  - 5: exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 - 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1: and 4: also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1: and 2: significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively.

10.
Neurosurgery ; 89(6): 1033-1041, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34634113

RESUMO

BACKGROUND: Trials of lumbar spondylolisthesis are difficult to compare because of the heterogeneity in the populations studied. OBJECTIVE: To define patterns of clinical presentation. METHODS: This is a study of the prospective Quality Outcomes Database spondylolisthesis registry, including patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis. Twenty-four-month patient-reported outcomes (PROs) were collected. A k-means clustering analysis-an unsupervised machine learning algorithm-was used to identify clinical presentation phenotypes. RESULTS: Overall, 608 patients were identified, of which 507 (83.4%) had 24-mo follow-up. Clustering revealed 2 distinct cohorts. Cluster 1 (high disease burden) was younger, had higher body mass index (BMI) and American Society of Anesthesiologist (ASA) grades, and globally worse baseline PROs. Cluster 2 (intermediate disease burden) was older and had lower BMI and ASA grades, and intermediate baseline PROs. Baseline radiographic parameters were similar (P > .05). Both clusters improved clinically (P < .001 all 24-mo PROs). In multivariable adjusted analyses, mean 24-mo Oswestry Disability Index (ODI), Numeric Rating Scale Back Pain (NRS-BP), Numeric Rating Scale Leg Pain, and EuroQol-5D (EQ-5D) were markedly worse for the high-disease-burden cluster (adjusted-P < .001). However, the high-disease-burden cluster demonstrated greater 24-mo improvements for ODI, NRS-BP, and EQ-5D (adjusted-P < .05) and a higher proportion reaching ODI minimal clinically important difference (MCID) (adjusted-P = .001). High-disease-burden cluster had lower satisfaction (adjusted-P = .02). CONCLUSION: We define 2 distinct phenotypes-those with high vs intermediate disease burden-operated for lumbar spondylolisthesis. Those with high disease burden were less satisfied, had a lower quality of life, and more disability, more back pain, and more leg pain than those with intermediate disease burden, but had greater magnitudes of improvement in disability, back pain, quality of life, and more often reached ODI MCID.

11.
Org Lett ; 23(21): 8482-8487, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641687

RESUMO

An elegant tandem reaction process for transferring N-allyl amide into CF2H-ß-amino alcohol is described. This approach proceeded smoothly under visible light irradiation in the presence of a 3 mol % Ir complex, exhibiting a broad substrate scope and functional group tolerance, and a variety of CF2H-ß-amino alcohols were readily accessed in good to excellent yields under mild conditions. The reliable mechanistic studies revealed that sequential difluoromethyl radical addition/carbocation trap/rearrangement is involved.

12.
Chin J Dent Res ; 24(3): 177-183, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491012

RESUMO

OBJECTIVE: To assess the prevalence, location, diameter, course and anastomosis of the lateral lingual foramina (LLF) and canals (LLCs) in a northern Chinese population using CBCT. METHODS: CBCT images of 506 patients (181 male and 325 female, mean age 21.03 ± 8.11 years) were collected. The prevalence, location, diameter, length, angle and anastomosis of the LLF and LLCs were assessed. The measurement variables were analysed by sex and age. Statistical analysis was performed using SPSS (v. 25, IBM, Armonk, NY, USA). RESULTS: A total of 461 LLF were detected in 307 (60.7%) subjects, 175 (57.0%) of whom had unilateral LLF and 132 (43.0%) of whom had bilateral LLF, with each lateral having one to four LLF. The majority of LLF (375/461, 81.3%) were located below the premolars, particularly the first premolar. The mean diameter of the LLF was 0.58 ± 0.20 mm. The mean vertical distance from the LLF to the inferior border and the alveolar crest was 6.68 ± 1.43 mm and 23.65 ± 2.89 mm, respectively. In total, 197 LLCs were visible in the cancellous bone and evaluated. The mean length of LLCs was 6.26 ± 1.29 mm, and the mean angle of LLCs was 140.64° ± 17.29°. The overwhelming majority (93.4%) of LLCs communicated with the mandibular incisive canal and the rest connected with the mandibular canal. CONCLUSION: The prevalence of LLCs was high in the northern Chinese population. The presence of LLCs is a significant predictor of communication with the mandibular incisive canal.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Adolescente , Adulto , Processo Alveolar , Criança , China , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Adulto Jovem
13.
J Neurosurg Spine ; : 1-8, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34534963

RESUMO

OBJECTIVE: Reduction of Meyerding grade is often performed during fusion for spondylolisthesis. Although radiographic appearance may improve, correlation with patient-reported outcomes (PROs) is rarely reported. In this study, the authors' aim was to assess the impact of spondylolisthesis reduction on 24-month PRO measures after decompression and fusion surgery for Meyerding grade I degenerative lumbar spondylolisthesis. METHODS: The Quality Outcomes Database (QOD) was queried for patients undergoing posterior lumbar fusion for spondylolisthesis with a minimum 24-month follow-up, and quantitative correlation between Meyerding slippage reduction and PROs was performed. Baseline and 24-month PROs, including the Oswestry Disability Index (ODI), EQ-5D, Numeric Rating Scale (NRS)-back pain (NRS-BP), NRS-leg pain (NRS-LP), and satisfaction (North American Spine Society patient satisfaction questionnaire) scores were noted. Multivariable regression models were fitted for 24-month PROs and complications after adjusting for an array of preoperative and surgical variables. Data were analyzed for magnitude of slippage reduction and correlated with PROs. Patients were divided into two groups: < 3 mm reduction and ≥ 3 mm reduction. RESULTS: Of 608 patients from 12 participating sites, 206 patients with complete data were identified in the QOD and included in this study. Baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts except for depression, listhesis magnitude, and the proportion with dynamic listhesis (which were accounted for in the multivariable analysis). One hundred four (50.5%) patients underwent lumbar decompression and fusion with slippage reduction ≥ 3 mm (mean 5.19, range 3 to 11), and 102 (49.5%) patients underwent lumbar decompression and fusion with slippage reduction < 3 mm (mean 0.41, range 2 to -2). Patients in both groups (slippage reduction ≥ 3 mm, and slippage reduction < 3 mm) reported significant improvement in all primary patient reported outcomes (all p < 0.001). There was no significant difference with regard to the PROs between patients with or without intraoperative reduction of listhesis on univariate and multivariable analyses (ODI, EQ-5D, NRS-BP, NRS-LP, or satisfaction). There was no significant difference in complications between cohorts. CONCLUSIONS: Significant improvement was found in terms of all PROs in patients undergoing decompression and fusion for lumbar spondylolisthesis. There was no correlation with clinical outcomes and magnitude of Meyerding slippage reduction.

14.
Front Oncol ; 11: 701492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527580

RESUMO

Background: Lymphoma-associated macrophages (LAMs) are key components in the lymphoma microenvironment, which may impact disease progression and response to therapy. There are two major subtypes of LAMs, CD68+ M1 and CD163+ M2. M2 LAMs can be transformed from M1 LAMs, particularly in certain diffuse large B-cell lymphomas (DLBCL). While mantle cell lymphoma (MCL) is well-known to contain frequent epithelioid macrophages, LAM characterization within MCL has not been fully described. Herein we evaluate the immunophenotypic subclassification, the expression of immune checkpoint molecule PD-L1, and the prognostic impact of LAMs in MCL. Materials and Methods: A total of 82 MCL cases were collected and a tissue microarray block was constructed. Immunohistochemical staining was performed using CD68 and CD163, and the positive cells were recorded manually in four representative 400× fields for each case. Multiplexed quantitative immunofluorescence assays were carried out to determine PD-L1 expression on CD68+ M1 LAMs and CD163+ M2 LAMs. In addition, we assessed Ki67 proliferation rate of MCL by an automated method using the QuPath digital imaging analysis. The cut-off points of optimal separation of overall survival (OS) were analyzed using the X-Tile software, the SPSS version 26 was used to construct survival curves, and the log-rank test was performed to calculate the p-values. Results: MCL had a much higher count of M1 LAMs than M2 LAMs with a CD68:CD163 ratio of 3:1. Both M1 and M2 LAMs were increased in MCL cases with high Ki67 proliferation rates (>30%), in contrast to those with low Ki67 (<30%). Increased number of M1 or M2 LAMs in MCL was associated with an inferior OS. Moreover, high expression of PD-L1 on M1 LAMs had a slightly better OS than the cases with low PD-L1 expression, whereas low expression of PD-L1 on M2 LAMs had a slightly improved OS, although both were not statistically significant. Conclusions: In contrast to DLBCL, MCL had a significantly lower rate of M1 to M2 polarization, and the high levels of M1 and M2 LAMs were associated with poor OS. Furthermore, differential PD-L1 expressions on LAMs may partially explain the different functions of tumor-suppressing or tumor-promoting of M1 and M2 LAMs, respectively.

15.
Front Cell Dev Biol ; 9: 668947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485273

RESUMO

Circular RNAs (circRNA) have been reported to exert evident functions in many human carcinomas. However, the possible mechanisms concerning the circRNA in various tumors are still elusive. In this research, we analyzed the expression profile and biological functions of circular RNA CDYL (circCDYL, circBase ID: hsa_circ_0008285) in Wilms' tumor. Here, miRNA and gene expression were examined by real-time PCR in Wilms' tumor tissues and cell lines. The functions of circCDYL and its potential targets to influence cell proliferation, migration, and invasion in Wilms' tumor cells were determined by biological functional experiments in vitro and in vivo. We predicted and analyzed potential miRNA targets through online bioinformatic tools. To validate the interactions between circCDYL and its targets, we performed RNA fluorescence in situ hybridization, biotin-coupled miRNA capture assay, and biotin-coupled probe pull-down assay. Tight junction protein l (TJP1) was proved to be the target gene of the predicted miRNA by dual-luciferase reporter assay. The expression level of TJP1 in Wilms' tumor cells was identified via Western blot. We showed that circCDYL was downregulated in WT tissue compared with adjacent non-tumor tissue. Upregulation of circCDYL could reduce cell proliferation, migration, and invasion. Mechanically, circCDYL, functioning as a miRNA sponge, decreased the expression level of miR-145-5p and TJP1 3'UTR was validated as the target of miR-145-5p, facilitating the circCDYL/miR-145-5p/TJP1 axis. In conclusion, our study suggested circCDYL as a novel biomarker and therapeutic target for WT treatment.

16.
J Cancer ; 12(20): 6126-6134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539885

RESUMO

Purpose: To investigate the prognostic significance of programmed cell death ligand-1 (PD-L1) and phosphorylated ERK (p-ERK) and their interactions in T-cell lymphoma (TCL). Methods: The mRNA levels of PD-L1 and ERK in TCL samples were analyzed. Formalin-fixed paraffin-embedded tissues from 69 TCL patients were collected to detect the expression of PD-L1 and p-ERK by multiplexed immunofluorescence staining. The total PD-L1 and p-ERK was measured by western blotting, and membrane PD-L1 was determined using flow cytometry. Results: PD-L1 and ERK mRNA levels were significantly upregulated in TCL. The expression rates of PD-L1 and p-ERK were 52.2% and 27.5%, respectively. PD-L1 expression correlated with stage (R=0.304, P=0.011) and IPI score (R=0.313, P=0.009), and p-ERK expression correlated with stage (R=0.330, P=0.006) and IPI score (R=0.376, P=0.002). PD-L1 expression positively correlated with p-ERK expression (R=0.355, P=0.003). Patients with co-expression of PD-L1 and p-ERK had the worst overall survival (P=0.007). In three TCL cell lines with PD-L1 expression, we demonstrated that the expression of p-ERK was upregulated after stimulation with PD-1, suggesting that ERK signaling was activated. Conclusions: The PD-1/PD-L1 axis activates intracellular ERK signaling in tumor cells and that PD-L1, p-ERK or their combination are potential biomarkers for predicting the prognosis in TCL patients.

17.
Genes Dis ; 8(6): 814-826, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34522710

RESUMO

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009, Sato et al established a three-dimensional culture system, which mimicked the niche microenvironment by employing the niche factors, and successfully grew crypt ISCs into organoids or Mini-guts in vitro. Since then, the intestinal organoid technology has been used to delineate cellular signaling in ISC biology. However, the cultured organoids consist of heterogeneous cell populations, and it was technically challenging to introduce genomic changes into three-dimensional organoids. Thus, there was a technical necessity to develop a two-dimensional ISC culture system for effective genomic manipulations. In this study, we established a conditionally immortalized mouse intestinal crypt (ciMIC) cell line by using a piggyBac transposon-based SV40 T antigen expression system. We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition, retained the biological characteristics of intestinal epithelial stem cells, and could form intestinal organoids in three-dimensional culture. While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic, the ciMICs overexpressing oncogenic ß-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo. Collectively, these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.

18.
Genes Dis ; 8(6): 918-930, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34522718

RESUMO

As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However, the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs, especially microRNAs, may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins, Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs), which are critical for small RNA biogenesis. Here, we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of Ago1, Ago2 and Ago3 in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes, we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore, we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization, and ectopic bone formation. Collectively, our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

19.
Antioxidants (Basel) ; 10(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34572977

RESUMO

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, and it is often associated with a high mortality rate and significant morbidity among survivors. Recent studies have shown that bilirubin, a product of heme metabolism, can exhibit cytoprotective, antioxidant and, anti-inflammatory properties. However, little is known about the role of bilirubin in combating several pathophysiological pathways caused by intracerebral bleeding in patients with ICH. In this study, data were collected retrospectively on 276 patients with ICH who were admitted to a university hospital between 5 January 2014 and 31 December 2017. We assessed the relationship between levels of total, direct, and indirect serum bilirubin and assessments of initial stroke severity and clinical outcomes by using Spearman's rank correlation and Kruskal-Wallis H tests. A secondary examination of the carrier protein albumin was also undertaken. Our study found that higher levels of direct bilirubin were correlated with worse admission Glasgow Coma Scales (GCS) (rs = -0.17, p = 0.011), worse admission ICH Scores (rs = 0.19, p = 0.008), and worse discharge modified Rankin Scales (mRS) (rs = 0.15, p = 0.045). Direct bilirubin was still significantly correlated with discharge mRS after adjusting for temperature at admission (rs = 0.16, p = 0.047), oxygen saturation at admission (rs = 0.15, p = 0.048), white blood cell count (rs = 0.18, p = 0.023), or Troponin T (rs = 0.25, p = 0.001) using partial Spearman's correlation. No statistical significance was found between levels of total or indirect bilirubin and assessments of stroke severity and outcomes. In contrast, higher levels of albumin were correlated with better admission GCS (rs = 0.13, p = 0.027), discharge GCS (rs = 0.15, p = 0.013), and discharge mRS (rs = -0.16, p = 0.023). We found that levels of total bilirubin, direct bilirubin, and albumin were all significantly related to discharge outcomes classified by discharge destinations (p = 0.036, p = 0.014, p = 0.016, respectively; Kruskal-Wallis H tests). In conclusion, higher direct bilirubin levels were associated with greater stroke severity at presentation and worse outcomes at discharge among patients with ICH. Higher levels of albumin were associated with lower stroke severity and better clinical outcomes. Future prospective studies on the free bioactive bilirubin are needed to better understand the intricate relationships between bilirubin and ICH.

20.
BMC Infect Dis ; 21(1): 919, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488677

RESUMO

BACKGROUND: Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS. METHODS: 63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p < 0.0001; hs-CRP, p < 0.0001), and PLT was significantly lower than that in the control group (p < 0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors were significantly decreased (p < 0.0001) and PLT significantly improved (p = 0.0216). With RIP3 > 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT < 204.00 × 109/L as the positive criteria, the sensitivity values of the three indicators in the diagnosis of LOS were 69.8%, 60.3%, 60.3%, respectively, and the specificity values were 92.4%, 96.2%, 79.8%, respectively. The combination of RIP3, hs-CRP and PLT had a sensitivity of 77.8% and specificity of 97.5%. CONCLUSIONS: RIP3 may contribute to the early diagnosis of LOS and monitoring of treatment effect. The combined detection of RIP3, hs-CRP and PLT may be more effective than individual detection in the diagnosis of LOS.


Assuntos
Sepse , Biomarcadores , Proteína C-Reativa/análise , Diagnóstico Precoce , Humanos , Recém-Nascido , Contagem de Plaquetas , Curva ROC , Sepse/diagnóstico
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