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1.
J Biomech Eng ; 144(3)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34505126

RESUMO

Plate fractures after fixation of a Vancouver Type B1 periprosthetic femoral fracture (PFF) are difficult to treat and could lead to severe disability. However, due to the lack of direct measurement of in vivo performance of the PFF fixation construct, it is unknown whether current standard mechanical tests or previous experimental and computational studies have appropriately reproduced the in vivo mechanics of the plate. To provide a basis for the evaluation and development of appropriate mechanical tests for assessment of plate fracture risk, this study applied loads of common activities of daily living (ADLs) to implanted femur finite element (FE) models with PFF fixation constructs with an existing or a healed PFF. Based on FE simulated plate mechanics, the standard four-point-bend test adequately matched the stress state and the resultant bending moment in the plate as compared with femur models with an existing PFF. In addition, the newly developed constrained three-point-bend tests were able to reproduce plate stresses in models with a healed PFF. Furthermore, a combined bending and compression cadaveric test was appropriate for risk assessment including both plate fracture and screw loosening after the complete healing of PFF. The result of this study provides the means for combined experimental and computational preclinical evaluation of PFF fixation constructs.

2.
Chemosphere ; 287(Pt 3): 132358, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34583294

RESUMO

Previous studies suggested immunotoxicity of perfluoroalkyl substances (PFASs), but contradictory findings were reported for the associations of PFASs with allergies. The current study aimed to investigate the association of serum PFASs with incident chronic spontaneous urticaria (CSU) in adults. A nested case-control study within a longitudinal cohort of 7051 government employees in China was conducted. Participants with urticaria at the baseline were excluded. During the first follow-up, 70 incident CSU cases were included, and 70 matched healthy controls were randomly selected. In serum samples collected at the baseline, eight PFASs were determined using the UHPLC-MS/MS approach. The median serum concentrations of perfluorobutanoic acid (PFBA) and perfluoroheptanoic acid (PFHpA) were significantly higher in participants with incident CSU. The area under the receiver operating characteristic curve was 0.714 (95% CI: 0.60-0.83) based on the joint prediction by PFBA and PFHpA. The Bayesian kernel machine regression showed a nonlinear positive overall effect of the mixture of PFASs, and identified significant single effects of PFBA and PFHpA. Serum interleukin-4 was significantly higher in the case group at baseline, and was positively associated with PFHpA (r = 0.24). Causal mediation analysis indicated interleukin-4 as a partial mediator (14.8%) in the association of PFHpA with CSU. In conclusion, serum PFASs are associated with an increased risk of incident CSU, and PFBA and PFHpA might be the effective compounds.


Assuntos
Ácidos Alcanossulfônicos , Urticária Crônica , Fluorcarbonetos , Adulto , Teorema de Bayes , Estudos de Casos e Controles , Fluorcarbonetos/toxicidade , Humanos , Espectrometria de Massas em Tandem
3.
Carbohydr Polym ; 276: 118766, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823786

RESUMO

The crystal structures of cellulose nanomaterials play an important role in their morphologies and applications, however, there was still lacking systematic research on preparing various crystalline allomorphs of cellulose nanocrystals with high thermal stability. Herein, the efficient synthesis route was presented to design various crystalline allomorphs of cellulose from cotton. And then, cellulose nanocrystals with different crystal structures (CNC-I, CNC-II, CNC-IIIII, CNC-IVII) were prepared by hydrogen peroxide hydrolysis of resultant cellulose. Overall, needle-like CNC-I (length of 180 ± 25 nm, diameter of 12 ± 2 nm), near-spherical CNC-II (diameter of 101 ± 12 nm), and spherical CNC-IIIII (diameter of 22 ± 3 nm) and CNC-IVII (diameter of 21 ± 2 nm) all exhibited remarkable dispersibility and thermal stability (Tmax > 357 °C). This work provides a simple and low-cost synthesis route for various crystalline allomorphs of CNCs with high thermal stability from the same raw materials (cotton).

4.
Dis Markers ; 2021: 1171239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853619

RESUMO

Background: Accurate analysis of intestinal microbiota will facilitate establishment of an evaluating system for assessing colorectal cancer (CRC) risk and prognosis. This study evaluates the potential role of Fusobacterium nucleatum (F. nucleatum) and Escherichia coli with a pks gene (pks+ E. coli) in early CRC diagnosis. Methods: We recruited 139 patients, including CRC (n = 60), colorectal adenomatous polyposis (CAP) (n = 37), and healthy individuals (n = 42) based on their colonoscopy examinations. We collected stool and serum samples from the participants and measured the relative abundance of F. nucleatum and pks+ E. coli in fecal samples by quantitative PCR. Receiver operating characteristic curve (ROC) analyses were used to analyze the diagnostic value of single or combined biomarkers. Results: Fecal F. nucleatum and pks+ E. coli levels were higher in the CRC group in either the CAP group or healthy controls (P = 0.02; 0.01). There was no statistical difference in the distribution of F. nucleatum and pks+ E. coli in patients with different tumor sites (P > 0.05). The combination of F. nucleatum+pks+ E. coli+CEA+CA19-9+FOBT was chosen as the optimal panel in differentiating both CRC and CAP from the controls. The combination of F. nucleatum, pks+ E. coli, and FOBT improved diagnostic efficiency. However, there was difficulty in differentiating CRC from CAP. Conclusion: Our results suggested that combining bacterial markers with conventional tumor markers improves the diagnostic efficiency for noninvasive diagnosis of CRC.

5.
Adv Mater ; : e2108793, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856022

RESUMO

Materials with strong magneto-structural coupling have complex energy landscapes featuring multiple local ground states, thus making it possible to switch among distinct magnetic-electronic properties. However, these energy minima are rarely accessible by a mere application of an external stimuli to the system in equilibrium state. Here, we report that a ferromagnetic ground state, with Tc above room temperature, can be created in an initially paramagnetic alloy by non-equilibrium nano-structuring. By dealloying process we transformed bulk chemically-disordered FeRh alloys into a nanoporous structure with a topology of a few nanometer-sized ligaments and nodes. Magnetometry and Mössbauer spectroscopy revealed the co-existence of two magnetic ground states - a conventional low-temperature spin glass and a hitherto-unknown robust ferromagnetic phase. The emergence of the ferromagnetic phase is validated by the density functional theory calculations showing that local tetragonal distortion induced by surface stress favors ferromagnetic ordering. Our study provides a means for reaching conventionally inaccessible magnetic states, resulting in a complete on/off ferromagnetic-paramagnetic switching over a broad temperature range. This article is protected by copyright. All rights reserved.

6.
Psychol Res Behav Manag ; 14: 1889-1900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858069

RESUMO

Objective: To explore the sleep quality and depression-anxiety-stress state of frontline nurses in high-risk areas who conduct nucleic acid sampling testing for COVID-19 to provide a basis for formulating intervention programs in crisis management. Methods: From August 22 to 30, 2021, a convenient sampling method was used in Zhangjiajie City, Hunan Province, China. A total of 248 frontline nurses who performed nucleic acid sample collection were selected. The following tests were used: the general information questionnaire, Pittsburgh Sleep Quality Questionnaire (PSQI), and Depression-Anxiety Stress Scale (DASS-21). Results: A total of 236 nurses completed the survey; 88.14% (n = 208) were women, the average age was 33.02±6.81, the PSQI score was 15 (13-17), and 231 (97.88%) nurses had sleep disorders during the period in Zhangjiajie, 219 nurses (81.36%) had anxiety, 135 nurses (45.76%) had depression, and 112 nurses (42.59%) felt stressed. Spearman correlation analysis was used to associate the PSQI with the DASS-21. The results showed that the use of hypnotic drugs was negatively correlated with DASS-21 (P<0.05), while the rest were positively correlated. The results of the multivariate analysis of sleep disorders showed that depression, anxiety, and stress were related to sleep quality (P<0.05), and there was no statistical difference in the other variables. Conclusion: During the COVID-19 pandemic, the sleep quality and depression-anxiety-stress state of the frontline nurses performing nucleic acid testing were adversely affected. Sleep disturbance is a serious problem among nurses testing for the delta strain during the pandemic. Anxiety, stress, and depression are associated with sleep disorders. It is necessary to take corresponding measures and conduct crisis management interventions to improve sleep quality and mental health adjustment during public health emergencies.

7.
Front Cell Infect Microbiol ; 11: 703126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858864

RESUMO

Background: Chronic urticaria (CU) is a chronic inflammatory skin disease associated with Th2 immune response. The two most common subtypes of CU, i.e., chronic spontaneous urticaria and symptomatic dermographism (CSD), often coexist. However, the pathogenesis of CSD is still unclear. Gut microbiota plays an important role in immune-related inflammatory diseases. The purpose of this study was to explore the correlation between gut microbiota and CSD. Methods: A case-control study was conducted on CSD patients as well as gender- and age-matched normal controls (NCs). The 16S ribosomal DNA sequencing of fecal samples was used to detect the gut microbiota of all subjects. QPCR was used to further verify the species with differences between the two groups. Results: The alpha diversity of gut microbiota decreased in CSD patients, accompanied by significant changes of the structure of gut microbiota. Subdoligranulum and Ruminococcus bromii decreased significantly in CSD patients and had a potential diagnostic value for CSD according to receiver operating characteristic curve (ROC) analysis. Enterobacteriaceae and Klebsiella were found to be positively correlated with the duration of CSD, while Clostridium disporicum was positively correlated with the dermatology life quality index (DLQI). Conclusions: The gut microbiota of CSD patients is imbalanced. Subdoligranulum and Ruminococcus bromii are the gut microbiota biomarkers in CSD.

8.
Front Public Health ; 9: 743368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858925

RESUMO

Objectives: To investigate the association of gender, ethnicity, living region, and socioeconomic status (SES) with health literacy and attitudes toward nevi and melanoma in Chinese adolescents and to examine whether health literacy mediates the association of SES with attitudes. Study Design: A multicenter cross-sectional study was conducted among newly enrolled college students. First-year students were recruited from five universities in different regions of China in 2018 using the cluster sampling method. The observers were blinded to the participants. Methods: Health literacy and attitudes were measured using a previously validated tool (Nevus and Melanoma Health Literacy and attitudes Test). SES was measured by annual family income and parental highest educational level. Nonparametric test was used to examine the association of participants' characteristics with health literacy and attitudes. Two-level generalized linear model with logarithm link function and Gamma distribution was used individually for SES. The mediation effect model was used to examine the mediation effect of health literacy. Results: A total of 21,086 questionnaires were completed by college students with a mean age of 18.0 ± 0.8 years. The mean scores of health literacy and attitudes were 9.83 ± 7.46 (maximum score: 28) and 16.98 ± 2.92 (maximum score: 20), respectively. Female, Han nationality, annual family income, and parental educational levels were positively associated with health literacy and attitudes. Regional differences showed different effects on health literacy and attitudes. A mediation model showed that literacy mediated the association of SES with attitudes toward nevi and melanoma. Health literacy mediated ~30-50% of the association of SES with attitudes. Conclusions: Melanoma-related health literacy among Chinese college students is generally insufficient and needs to be improved. Targeted and personalized health education for improving health literacy related to nevi and melanoma may improve the general population's attitudes and further promote health-related behavior to prevent and identify early-stage melanoma.

9.
Front Plant Sci ; 12: 731484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764965

RESUMO

Small nucleolar RNAs (snoRNAs) are a class of conserved nuclear RNAs that play important roles in the modification of ribosomal RNAs (rRNAs) in plants. In rubber trees, rRNAs are run off with latex flow during tapping and need to be regenerated for maintaining the functions of the laticifer cells. SnoRNAs are expected to play essential roles in the regeneration of rRNAs. However, snoRNAs in the rubber tree have not been sufficiently characterized thus far. In this study, we performed nuclear RNA sequencing (RNA-seq) to identify snoRNAs globally and investigate their roles in latex regeneration. We identified a total of 3,626 snoRNAs by computational prediction with nuclear RNA-seq data. Among these snoRNAs, 50 were highly expressed in latex; furthermore, the results of reverse transcription polymerase chain reaction (RT-PCR) showed the abundant expression of 31 of these snoRNAs in latex. The correlation between snoRNA expression and adjusted total solid content (TSC/C) identified 13 positively yield-correlated snoRNAs. To improve the understanding of latex regeneration in rubber trees, we developed a novel insulated tapping system (ITS), which only measures the latex regenerated in specific laticifers. Using this system, a laticifer-abundant snoRNA, HbsnoR28, was found to be highly correlated with latex regeneration. To the best of our knowledge, this is the first report to globally identify snoRNAs that might be involved in latex regeneration regulation and provide new clues for unraveling the mechanisms underlying the regulation of latex regeneration.

10.
Nat Commun ; 12(1): 6389, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737279

RESUMO

Focusing electromagnetic field to enhance the interaction with matter has been promoting researches and applications of nano electronics and photonics. Usually, the evanescent-wave coupling is adopted in various nano structures and materials to confine the electromagnetic field into a subwavelength space. Here, based on the direct coupling with confined electron oscillations in a nanowire, we demonstrate a tight localization of microwave field down to 10-6λ. A hybrid nanowire-bowtie antenna is further designed to focus the free-space microwave to this deep-subwavelength space. Detected by the nitrogen vacancy center in diamond, the field intensity and microwave-spin interaction strength are enhanced by 2.0 × 108 and 1.4 × 104 times, respectively. Such a high concentration of microwave field will further promote integrated quantum information processing, sensing and microwave photonics in a nanoscale system.

11.
Bosn J Basic Med Sci ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34784265

RESUMO

According to the previous reports, hypothyroidism has been shown to be strongly correlated with increased circulating concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Notably, thyroid hormones  are confirmed to modulate the production, clearance, and transformation process of cholesterol within circulation of mammals. Moreover, emerging evidence suggests that the thyroid-stimulating hormone could also participate in modulating serum lipid metabolism independently of thyroid hormones, which further induces the pathological development of dyslipidemia. However, the underlying mechanism is still not fully elucidated. Recently, several research studies have demonstrated that the pathogenic progression of hypothyroidism-related dyslipidemia might be correlated with the decreased serum concentrations of thyroid hormones and the increased serum concentrations of thyroid-stimulating hormones. Thus, this indicates that hypothyroidism could induce dyslipidemia and its related cardio-metabolic disorder diseases. In addition, several newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play an important role in the regulation of dyslipidemia induced by hypothyroidism. Furthermore, under the status of hypothyroidism, significantly dysfunctional HDL particles could also be observed. In the current review, we summarized the recent knowledge of the relationship between the development of hypothyroidism with dyslipidemia. We also discussed the updated understanding of the mechanisms whereby hypothyroidism induces the risk and the development of dyslipidemia and cardio-metabolic diseases.

12.
Bosn J Basic Med Sci ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34784266

RESUMO

Dyslipidemia has recently been identified as an important factor in modulating the progression of several health conditions, grouped as cardio-metabolic syndrome and including obesity,insulin resistance, and atherosclerosis. Among multiple factors which regulate the development of cardio-metabolic syndrome, sortilin has been found in multiple cell types, such as adipocyte, hepatocyte, and macrophage, suggesting that sortilin is correlated to the development and the severity of cardio-metabolic syndrome. Consistently, several genome-wide association  (GWAS) and basic experimental research studies are being conducted to find novel gene loci involved in regulating the pathological progression of cardio-metabolic syndrome. According to these data, both SORT1 gene and sortilin protein have an important function in regulating the circulating lipid and glucose metabolism resulting in modulation of disease progression. In this comprehensive review, we summarize the recent research results in regards to sortilin function in modulating the circulating lipid and glucose metabolism. Moreover, we also discuss and analyze the emerging evidence elucidating the potential mechanisms by which sortilin affects synthesis and secretion of lipid and glucose.

13.
Adv Sci (Weinh) ; : e2103065, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787377

RESUMO

Depression is a mental disorder affecting more than 300 million people in the world. Abnormalities in white matter are associated with the development of depression. Here, the authors show that mice with oligodendrocyte-specific deletion of Nerve injury-induced protein 2 (Ninj2) exhibit depressive-like behaviors. Loss of Ninj2 in oligodendrocytes inhibits oligodendrocyte development and myelination, and impairs neuronal structure and activities. Ninj2 competitively inhibits TNFα/TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of Ninj2 activates TNFα-induced necroptosis, and increases C-C Motif Chemokine Ligand 2 (Ccl2) production, which might mediate the signal transduction from oligodendrocyte to neurons. Inhibition of necroptosis by Nec-1s administration synchronously restores oligodendrocyte development, improves neuronal excitability, and alleviates depressive-like behaviors. This study thus illustrates the role of Ninj2 in the development of depression and myelination, reveals the relationship between oligodendrocytes and neurons, and provides a potential therapeutic target for depression.

15.
J Zhejiang Univ Sci B ; 22(11): 893-905, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34783220

RESUMO

Cathepsin D (CTSD), the major lysosomal aspartic protease that is widely expressed in different tissues, potentially regulates the biological behaviors of various cells. Follicular granulosa cells are responsive to the increase of ovulation number, hence indirectly influencing litter size. However, the mechanism underlying the effect of CTSD on the behaviors of goat granulosa cells has not been fully elucidated. This study used immunohistochemistry to analyze CTSD localization in goat ovarian tissues. Moreover, western blotting was applied to examine the differential expression of CTSD in the ovarian tissues of monotocous and polytocous goats. Subsequently, the effects of CTSD knockdown on cell proliferation, apoptosis, cell cycle, and the expression of candidate genes of the prolific traits, including bone morphogenetic protein receptor IB (BMPR-IB), follicle-stimulating hormone (FSHR), and inhibin α (INHA), were determined in granulosa cells. Results showed that CTSD was expressed in corpus luteum, follicle, and granulosa cells. Notably, CTSD expression in the monotocous group was significantly higher than that in the polytocous group. In addition, CTSD knockdown could improve granulosa cell proliferation, inhibit cell apoptosis, and significantly elevate the expression of proliferating cell nuclear antigen (PCNA) and B cell lymphoma 2 (Bcl-2), but it lowered the expression of Bcl-2-associated X (Bax) and caspase-3. Furthermore, CTSD knockdown significantly reduced the ratios of cells in the G0/G1 and G2/M phases but substantially increased the ratio of cells in the S phase. The expression levels of cyclin D2 and cyclin E were elevated followed by the obvious decline of cyclin A1 expression. However, the expression levels of BMPR-IB, FSHR, and INHA clearly increased as a result of CTSD knockdown. Hence, our findings demonstrate that CTSD is an important factor affecting the litter size trait in goats by regulating the granulosa cell proliferation, apoptosis, cell cycle, and the expression of candidate genes of the prolific trait.

17.
Front Genet ; 12: 749435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804118

RESUMO

Background: Leptin receptor overlapping transcript (LEPROT) is reported to be involved in metabolism regulation and energy balance as well as molecular signaling of breast cancer and osteosarcoma. LEPROT is expressed in various tissue and is suggested to be involved in cancer developments but with contradictory roles. The comprehensive knowledge of the effects of LEPROT on cancer development and progression across pan-cancer is still missing. Methods: The expressions of LEPROT in cancers were compared with corresponding normal tissues across pan-cancer types. The relationships between expression and methylation of LEPROT were then demonstrated. The correlations of LEPROT with the tumor microenvironment (TME), including immune checkpoints, tumor immune cells infiltration (TII), and cancer-associated fibroblasts (CAFs), were also investigated. Co-expression analyses and functional enrichments were conducted to suggest the most relevant genes and the mechanisms of the effects in cancers for LEPROT. Finally, the correlations of LEPROT with patient survival and immunotherapy response were explored. Results: LEPROT expression was found to be significantly aberrant in 15/19 (78.9%) cancers compared with corresponding normal tissues; LEPROT was downregulated in 12 cancers and upregulated in three cancers. LEPROT expressions were overall negatively correlated with its methylation alterations. Moreover, LEPROT was profoundly correlated with the TME, including immune checkpoints, TIIs, and CAFs. According to co-expression analyses and functional enrichments, the interactions of LEPROT with the TME may be mediated by the interleukin six signal transducer/the Janus kinase/signal transducers and activators of the transcription signaling pathway. Prognostic values may exist for LEPROT to predict patient survival and immunotherapy response in a context-dependent way. Conclusions: LEPROT affects cancer development by interfering with the TME and regulating inflammatory or immune signals. LEPROT may also serve as a potential prognostic marker or a target in cancer therapy. This is the first study to investigate the roles of LEPROT across pan-cancer.

18.
Adv Sci (Weinh) ; : e2103277, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34723442

RESUMO

Variable stiffness catheters are typically composed of an encapsulated core. The core is usually composed of a low melting point alloy (LMPA) or a thermoplastic polymer (TP). In both cases, there is a need to encapsulate the core with an elastic material. This imposes a limit to the volume of variable stiffness (VS) material and limits miniaturization. This paper proposes a new approach that relies on the use of thermosetting materials. The variable stiffness catheter (VSC) proposed in this work eliminates the necessity for an encapsulation layer and is made of a unique biocompatible thermoset polymer with an embedded heating system. This significantly reduces the final diameter, improves manufacturability, and increases safety in the event of complications. The device can be scaled to sub-millimeter dimensions, while maintaining a high stiffness change. In addition, integration into a magnetic actuation system allows for precise actuation of one or multiple tools.

19.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(10): 1021-1026, 2021 Oct 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34719417

RESUMO

OBJECTIVES: To study the value of serum miR-922 and miR-506 expression levels in the diagnosis and prognostic assessment of childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 132 children with ALL (ALL group) and 80 healthy children (healthy control group) were prospectively selected in this study. Quantitative real-time polymerase chain reaction was used to measure the expression levels of serum miR-922 and miR-506 in both groups. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of miR-922 and miR-506 for childhood ALL. The Kaplan-Meier method was used to plot survival curves, and multivariate COX regression models were used to analyze the risk factors for poor prognosis in children with ALL. RESULTS: The ALL group had significantly higher expression levels of serum miR-922 and miR-506 than the control group (P<0.001). The ROC curve analysis showed that the optimal cut-off values of miR-922 and miR-506 for the diagnosis of childhood ALL were 1.46 and 2.17, respectively. The high miR-922 expression (≥1.46) group and high miR-506 expression (≥2.17) group had significantly higher incidence rates of lymph node enlargement, leukocyte count ≥50×109/L, medium-high risk stratification, mixed-lineage leukemia (MLL) gene rearrangement, and karyotype abnormality than the low miR-922 expression group and low miR-506 expression group (P<0.05). The Kaplan-Meier analysis showed that high expression of miR-922 and miR-506 was associated with short survival time in children with ALL (P<0.05). The multivariate COX regression analysis showed that leukocyte count ≥50×109/L, medium-high risk stratification, MLL gene rearrangement, miR-922≥1.46, and miR-506≥2.17 could indicate poor prognosis in children with ALL (P<0.05). CONCLUSIONS: The expression levels of miR-922 and miR-506 are of good value in the diagnosis and prognostic assessment of childhood ALL.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Biomarcadores Tumorais , Criança , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/sangue , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Curva ROC
20.
Mol Ther Oncolytics ; 23: 277-287, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34761107

RESUMO

The incidence of pancreatic neuroendocrine tumor (PNET) has continued to rise. Due to their indolent feature, PNET patients often present with incurable, metastatic diseases. Novel therapies are urgently needed. We have previously shown that Receptor for Hyaluronic Acid-Mediated Motility isoform B (RHAMMB) and Bcl-xL are upregulated in PNETs and both of them promote PNET metastasis. Because RHAMM protein is undetectable in most adult tissues, we hypothesized that RHAMMB could be a gateway for nanomedicine delivery into PNETs. To test this, we developed a RHAMMB-targeting nanoparticle (NP). Inside this NP, we assembled small interfering RNA (siRNA) against Bcl-xL (siBcl-xL) and mitochondria-fusing peptide KLA. We demonstrated that RHAMMB-positive PNETs picked up the RHAMMB-targeting NPs. siBcl-xL or KLA alone killed only 30% of PNET cells. In contrast, a synergistic killing effect was achieved with the co-delivery of siBcl-xL and KLA peptide in vitro. Unexpectedly, siBcl-xL induced cell death before reducing Bcl-xL protein levels. The systemically injected RHAMMB-targeting NPs carrying siBcl-xL and KLA peptide significantly reduced tumor burden in mice bearing RHAMMB-positive PNETs. Together, these findings indicate that the RHAMMB-targeting nanotherapy serves as a promising drug delivery system for PNET and possibly other malignancies with upregulated RHAMMB. The combination of siBcl-xL and KLA peptide can be a therapy for PNET treatment.

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