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Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.
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The size and axial alignment of prostheses, when planned during total knee replacement (TKA) are critical for recovery of knee function and improvement of knee pain symptoms. This research aims to study the effect of artificial intelligence (AI)-based preoperative three dimensional (3D) planning technology on prosthesis size and axial alignment planning in TKA, and to compare its advantages with two dimensional (2D) X-ray template measurement technology. A total of 60 patients with knee osteoarthritis (KOA) who underwent TKA for the first time were included in the AI (n = 30) and 2D (n = 30) groups. The preoperative and postoperative prosthesis size, femoral valgus correction angle (VCA) and hip-knee-ankle angle (HKA) were recorded and compared between the two groups. The results of the University of Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the American Knee Association Score (AKS) were evaluated before surgery, 3 months, 6 months, and 12 months after surgery. The accuracy of prosthesis size, VCA and HKA prediction in AI group was significantly higher than that in 2D group (P < 0.05). The WOMAC and AKS scores in AI group at 3 months, 6 months and 12 months after surgery were better than those in 2D group (P < 0.05). Both groups showed significant improvement in WOMAC and AKS scores at 12 months follow-up. AI-based preoperative 3D planning technique has more reliable planning effect for prosthesis size and axial alignment in TKA.
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Artroplastia de Reemplazo de Rodilla , Inteligencia Artificial , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Imagenología Tridimensional/métodos , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Cuidados Preoperatorios/métodos , Periodo PreoperatorioRESUMEN
Lung cancer is one of the most common malignancies worldwide, with non-small cell lung cancer (NSCLC) being the most common type. As understanding of precise treatment options for NSCLC deepens, circulating tumor DNA (ctDNA) has emerged as a potential biomarker that has become a research hotspot and may represent a new approach for the individualized diagnosis and treatment of NSCLC. This article reviews the applications of ctDNA for the early screening of patients with NSCLC, guiding targeted therapy and immunotherapy, evaluating chemotherapy and postoperative efficacy, assessing prognosis and monitoring recurrence. With the in-depth study of the pathogenesis of NSCLC, plasma ctDNA may become an indispensable part of the precise treatment of NSCLC, which has great clinical application prospects.
[Box: see text].
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Acupuncture has obvious therapeutic effect on intracerebral hemorrhage (ICH). miR-34a-5p regulated by acupuncture was found to attenuate neurological deficits in ICH. However, the underlying mechanisms are unclear. Ubiquitin Like 4A (UBL4A) has not been studied in ICH. SD rats were injected with autologous blood to induce ICH and treated with Baihui-penetrating-Qubin acupuncture. Acupuncture resulted in an increase in forelimb placing test scores, and a decrease in corner test scores and brain water content of ICH rats. Histopathological examination showed that acupuncture inhibited ICH-induced inflammation, decreased damaged neurons and increased UBL4A expression. UBL4A overexpression increased cell viability, inhibited apoptosis, reduced ROS level and increased MnSOD activity, mitochondrial membrane potential and mtDNA level in rat embryonic primary cortical neurons. miR-34a-5p knockdown increased UBL4A expression, apoptosis rate and ROS level in hemin-treated neurons. Dual luciferase assays showed that miR-34a-5p bound to UBL4A. Apoptotic cells and ROS level were increased in hemin-treated neurons with UBL4A and miR-34a-5p knockdown. We firstly demonstrate the inhibitory effect of UBL4A on neuronal apoptosis, and the regulation relationship between UBL4A and miR-34a-5p. This study provides a new candidate target for ICH treatment and more basis for elucidating the molecular mechanism of acupuncture. In the future, we will conduct a deeper exploration of the effects of UBL4A on ICH.
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To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on the similarity between the phenotype of primates and humans. We screened out patients with LMD and compared the clinical data of LMD with TTN-mutated and mutation-free dilated cardiomyopathy to obtain the unique phenotype. After establishment of the LMNA c.357-2A>G primate model, primates were continuously observed for 48 months, and echocardiographic, electrophysiological, histologic, and transcriptional data were recorded. The LMD primate model was found to highly simulate the phenotype of clinical LMD. In addition, the LMD primate model shared a similar natural history with humans.
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BACKGROUND/AIMS: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. METHODS: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. RESULTS: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. CONCLUSION: For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.
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Anemia , Eritropoyetina , Glicina , Hematínicos , Hemoglobinas , Isoquinolinas , Diálisis Peritoneal , Humanos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Anemia/tratamiento farmacológico , Anemia/etiología , Anemia/sangre , Eritropoyetina/uso terapéutico , Eritropoyetina/efectos adversos , Resultado del Tratamiento , Glicina/análogos & derivados , Glicina/uso terapéutico , Glicina/efectos adversos , Anciano , Isoquinolinas/uso terapéutico , Isoquinolinas/efectos adversos , Diálisis Peritoneal/efectos adversos , Hematínicos/uso terapéutico , Hematínicos/efectos adversos , Hemoglobinas/metabolismo , Adulto , Factores de Tiempo , Biomarcadores/sangre , Inhibidores de Prolil-Hidroxilasa/uso terapéutico , Inhibidores de Prolil-Hidroxilasa/efectos adversosRESUMEN
OBJECTIVE: Common peroneal nerve (CPN) injury is a frequently encountered lower extremity injury. Furthermore, several previous studies have demonstrated that patients who underwent direct suturing of the CPN following rupture experienced unfavorable postoperative prognoses. Therefore, we aimed to present a novel modified surgical approach for CPN rupture and assess the effectiveness of this technique in restoring lower limb functionality. METHODS: In this retrospective observational study, we included patients with CPN rupture who underwent one-stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap for CPN rupture between January 2016 and December 2020. Lower limb function was evaluated using the lower extremity functional scale (LEFS) and British Medical Research Council (BMRC) grading system. We also assessed the influence of age, sex, duration of symptoms, mechanism of injury, and surgical modality on the postoperative recovery of lower extremity function using subgroup and regression analyses. RESULTS: Thirty-seven patients (mean age = 35.76 ± 13.01 years) with at least 2 years of follow-up were included in the final analysis. The LEFS scores significantly improved after surgery at the last follow-up (p < 0.01). Moreover, 67.57% of the patients achieved good or excellent postoperative outcomes (BMRC: M3 or above). Results of the subgroup analysis and regression models suggested that patients who underwent direct suturing showed better recovery of lower extremity function than those who underwent nerve grafting. CONCLUSION: One-stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap exhibited encouraging outcomes in restoring lower-limb function among patients with CPN rupture. This novel surgical technique is expected to be an effective method for treating CPN ruptures in the future.
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Neuropatías Peroneas , Procedimientos de Cirugía Plástica , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Nervio Peroneo/cirugía , Nervio Peroneo/lesiones , Músculo Esquelético/cirugía , Colgajos Quirúrgicos , Estudios RetrospectivosRESUMEN
In addition to long-distance molecular motor-mediated transport, cellular vesicles also need to be moved at short distances with defined directions to meet functional needs in subcellular compartments but with unknown mechanisms. Such short-distance vesicle transport does not involve molecular motors. Here, we demonstrate, using synaptic vesicle (SV) transport as a paradigm, that phase separation of synaptic proteins with vesicles can facilitate regulated, directional vesicle transport between different presynaptic bouton sub-compartments. Specifically, a large coiled-coil scaffold protein Piccolo, in response to Ca2+ and via its C2A domain-mediated Ca2+ sensing, can extract SVs from the synapsin-clustered reserve pool condensate and deposit the extracted SVs onto the surface of the active zone protein condensate. We further show that the Trk-fused gene, TFG, also participates in COPII vesicle trafficking from ER to the ER-Golgi intermediate compartment via phase separation. Thus, phase separation may play a general role in short-distance, directional vesicle transport in cells.
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Vesículas Cubiertas por Proteínas de Revestimiento , Retículo Endoplásmico , Vesículas Sinápticas , Animales , Vesículas Sinápticas/metabolismo , Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Retículo Endoplásmico/metabolismo , Calcio/metabolismo , Aparato de Golgi/metabolismo , Ratas , Transporte Biológico , Terminales Presinápticos/metabolismo , Sinapsinas/metabolismo , Condensados Biomoleculares/metabolismo , Proteínas del Citoesqueleto/metabolismo , Separación de FasesRESUMEN
BACKGROUND: The extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarcoma. METHOD: In this study, we used RNA sequencing to assess whether the recently invented membrane-anchored and tumor-targeted IL-12-armed (attIL12) T cells, which bind cell-surface vimentin (CSV) on tumor cells, could destroy CAFs to disrupt the ECM. We established an in vitro model of the interaction between osteosarcoma CAFs and attIL12-T cells to uncover the underlying mechanism by which attIL12-T cells penetrate stroma-enriched osteosarcoma tumors. RESULTS: RNA sequencing demonstrated that attIL12-T cell treatment altered ECM-related gene expression. Immunohistochemistry staining revealed disruption or elimination of high-density CAFs and ECM in osteosarcoma xenograft tumors following attIL12-T cell treatment, and CAF/ECM density was inversely correlated with T-cell infiltration. Other IL12-armed T cells, such as wild-type IL-12-targeted or tumor-targeted IL-12-T cells, did not disrupt the ECM because this effect depended on the engagement between CSV on the tumor cell and its ligand on the attIL12-T cells. Mechanistic studies found that attIL12-T cell treatment elevated IFNγ production on interacting with CSV+ tumor cells, suppressing transforming growth factor beta secretion and in turn upregulating FAS-mediated CAF apoptosis. CAF destruction reshaped the tumor stroma to favor T-cell infiltration and tumor inhibition. CONCLUSIONS: This study unveiled a novel therapy-attIL12-T cells-for targeting CAFs/ECM. These findings are highly relevant to humans because CAFs are abundant in human osteosarcoma.
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Neoplasias Óseas , Fibroblastos Asociados al Cáncer , Osteosarcoma , Animales , Humanos , Interleucina-12 , Xenoinjertos , Osteosarcoma/terapia , Membrana Celular , Matriz Extracelular , Modelos Animales de Enfermedad , Neoplasias Óseas/terapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Objective: To investigate the clinical efficacy of beraprost sodium (BPS) in the treatment of chronic kidney disease (CKD). Methods: In this single-centre, prospective, controlled, single-blind study, 252 patients diagnosed with CKD and treated at the Affiliated Hospital of Xuzhou Medical University were enrolled from September 2018 to June 2021. All participants were randomised into three groups: the control, BPS 40 µg, and BPS 20 µg groups. Both treatment groups were administered conventional therapy for 6 months. Renal function in the three groups was measured and compared 3 and 6 months post-treatment. Results: 1. Renal function in the BPS 20 µg and BPS 40 µg groups was better than that in the control group after 3 and 6 months of treatment. 2. After 3 months of treatment, the levels of serum creatinine (P = 0.043), cystatin C (P = 0.039), and 24 h urinary total protein (P = 0.041) in the BPS 40 µg group were significantly lower than those in the BPS 20 µg group, the eGFR (P = 0.046) level was higher than that in the BPS 20 µg group, and the index improvement rate was better than that in the BPS 20 µg group (P < 0.05). 3. After 6 months of treatment, the improvement in renal function in the BPS 20 µg group was close to that in the BPS 40 µg group (P > 0.05). Conclusion: BPS improved renal function, reduced urinary protein levels, and delayed CKD progression. The clinical efficacy of BPS in the 40 µg group was faster than that in the BPS 20 µg group. The long-term use of BPS is effective in patients with CKD.
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The use of an appropriate preparation route is the key to immobilize active molecules into a host matrix with high loadings and stability. Herein, we demonstrate a simple and general strategy to immobilize ferrocene and its derivatives into ZIF-8 with high loadings of up to 4.3% Fe content. The unique host pore structure allows for the stabilization of guest molecules and effectively prevents their leaching. As a result, the obtained electrocatalysts exhibit competitive oxygen evolution reaction (OER) catalytic performance. Optimized Fc-CHO/ZIF-8 requires only a low overpotential of 238 mV to achieve 10 mA cm-2, along with a relatively small Tafel slope of 44.4 mV dec-1. This performance is superior to that of commercial IrO2, suggesting its potential application in electrochemical energy conversion.
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The endoplasmic reticulum (ER), which is composed of a continuous network of tubules and sheets, forms the most widely distributed membrane system in eukaryotic cells. As a result, it engages a variety of organelles by establishing membrane contact sites (MCSs). These contacts regulate organelle positioning and remodeling, including fusion and fission, facilitate precise lipid exchange, and couple vital signaling events. Here, we systematically review recent advances and converging themes on ER-involved organellar contact. The molecular basis, cellular influence, and potential physiological functions for ER/nuclear envelope contacts with mitochondria, Golgi, endosomes, lysosomes, lipid droplets, autophagosomes, and plasma membrane are summarized.
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Retículo Endoplásmico , Mitocondrias , Retículo Endoplásmico/metabolismo , Humanos , Animales , Mitocondrias/metabolismo , Aparato de Golgi/metabolismo , Lisosomas/metabolismo , Endosomas/metabolismo , Transducción de Señal , Membrana Celular/metabolismo , Autofagosomas/metabolismo , Membrana Nuclear/metabolismo , Gotas Lipídicas/metabolismoRESUMEN
Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC. During the development of EAC, several intestinal-type proteins and signaling cascades are induced. The anti-inflammatory and immunosuppressive microenvironment is associated with poor survival. The accumulation of somatic mutations at the early phase and chromosomal structural rearrangements at relatively later time points contribute to the dynamic and heterogeneous genetic landscape of EAC. EAC is also characterized by frequent DNA methylation and dysregulation of microRNAs. We summarize the findings of dysregulations of specific cytokines, chemokines and immune cells in the tumor microenvironment and conclude that DNA methylation and microRNAs vary with each different phase of BE, LGD, HGD, early EAC and invasive EAC. Furthermore, we discuss the suitability of the currently employed therapies in the clinic and possible new therapies in the future. The development of targeted and immune therapies has been hampered by the heterogeneous genetic characteristics of EAC. In view of this, the up-to-date knowledge revealed by this work is absolutely important for future EAC studies and the discovery of new therapeutics.
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BACKGROUND: Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases. OBJECTIVES: The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis. METHODS: AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression. RESULTS: Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis via activating the SIX1/HBO1 signaling pathway. CONCLUSION: The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.
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BACKGROUND: Although COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic. METHODS: Based on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan-Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort. FINDINGS: Before matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15-180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18-39 years, but was not detected for those aged 40 years or older. INTERPRETATION: The receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage.
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Vacunas contra la COVID-19 , COVID-19 , Adulto Joven , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios de Cohortes , SARS-CoV-2RESUMEN
Despite innovations in cancer therapeutics, cancer remains associated with high mortality and is one of biggest health challenges worldwide. Therefore, developing precise cancer imaging and effective treatments is an unmet clinical need. A relatively novel type of therapeutics are heavy chain variable domain antibody fragments (VHHs) derived from llamas. Here, we explored the suitability of VHHs for cancer imaging and therapy through reviewing the existing literature. We searched the MEDLINE, EMBASE and Cochrane databases and identified 32 papers on molecular imaging and 41 papers on therapy that were suitable for comprehensive reviewing. We found that VHHs harbor a higher specificity and affinity compared to mAbs, which contributes to high-quality imaging and less side-effects on healthy cells. The employment of VHHs in cancer imaging showed remarkably shorter times between administration and imaging. Studies showed that 18F and 99mTc are two optimal radionuclides for imaging with VHHs and that site-specific labelling is the optimal conjugation modality for VHHs with radionuclide or fluorescent molecules. We found different solutions for reducing kidney retention and immunogenicity of VHHs. VHHs as anticancer therapeutics have been tested in photodynamic therapy, targeted radionuclide therapy, immunotherapy and molecular targeted therapy. These studies showed that VHHs target unique antigen epitopes, which are distinct from the ones recognized by mAbs. This advantage means that VHHs may be more effective for targeted anticancer therapy and can be combined with mAbs. We found that high cellular internalization and specificity of VHHs contributes to the effectiveness and safety of VHHs as anticancer therapeutics. Two clinical trials have confirmed that VHHs are effective and safe for cancer imaging and therapy. Together, VHHs seem to harbor several advantages compared to mAbs and show potential for application in personalized treatment for cancer patients. VHH-based imaging and therapy are promising options for improving outcomes of cancer patients.
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Metal-organic frameworks (MOFs) are promising electrocatalysts for clean energy conversion systems. However, developing MOF-based electrodes with high performance toward oxygen evolution reaction (OER) is still challenging. In this work, a series of MOF film electrodes derived from Ni-btz were prepared by employing the secondary growth strategy under solvothermal conditions. Fe and Co ions were also incorporated into the Ni-btz framework to produce a trimetallic coupling effect to obtain enhanced OER activity. The as-prepared FeCoNi-btz/NF exhibited not only good stability but also excellent OER performance under alkaline conditions. Furthermore, the possible intermediates including metal oxides and metal oxyhydroxides were confirmed by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM).
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Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral blood samples in 58 pediatric CNS tumor patients. In this study, we used a CSV-coated cell capture chip, the Abnova CytoQuest automated CTC isolation system, to boost the CTC capture from pediatric patients with CNS tumors. We successfully isolated CTCs in six glioma patients using immunostaining of histone H3 lysine27-to-methionine (H3K27M) mutations which are highly expressed by this tumor. We show that CSV is a viable marker for CNS CTC isolation and that this is a feasible method for detecting microscopic disease. Larger-scale studies focusing on CTCs in pediatric CNS tumors to explore their diagnostic and prognostic value are warranted.
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Fetal stages are critical periods for brain development. However, the protein molecular signature and dynamics of the human brain remain unclear due to sampling difficulty and ethical limitations. Non-human primates present similar developmental and neuropathological features to humans. This study constructed a spatiotemporal proteomic atlas of cynomolgus macaque brain development from early fetal to neonatal stages. Here we showed that (1) the variability across stages was greater than that among brain regions, and comparisons of cerebellum vs. cerebrum and cortical vs. subcortical regions revealed region-specific dynamics across early fetal to neonatal stages; (2) fluctuations in abundance of proteins associated with neural disease suggest the risk of nervous disorder at early fetal stages; (3) cross-species analysis (human, monkey, and mouse) and comparison between proteomic and transcriptomic data reveal the proteomic specificity and genes with mRNA/protein discrepancy. This study provides insight into fetal brain development in primates.
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Encéfalo , Proteómica , Animales , Encéfalo/metabolismo , Cerebelo , Desarrollo Fetal , Macaca fascicularisRESUMEN
PURPOSE: Flap endonuclease 1 (FEN1) is highly upregulated in prostate cancer and promotes the growth of prostate cancer cells. Androgen receptor (AR) is the most critical determinant of the occurrence, progression, metastasis, and treatment of prostate cancer. However, the effect of FEN1 on docetaxel (DTX) sensitivity and the regulatory mechanisms of AR on FEN1 expression in prostate cancer need to be further studied. METHODS: Bioinformatics analyses were performed using data from the Cancer Genome Atlas and the Gene Expression Omnibus. Prostate cancer cell lines 22Rv1 and LNCaP were used. FEN1 siRNA, FEN1 overexpression plasmid, and AR siRNA were transfected into cells. Biomarker expression was evaluated by immunohistochemistry and Western blotting. Apoptosis and the cell cycle were explored using flow cytometry analysis. Luciferase reporter assay was performed to verify the target relationship. Xenograft assays were conducted using 22Rv1 cells to evaluate the in vivo conclusions. RESULTS: Overexpression of FEN1 inhibited cell apoptosis and cell cycle arrest in the S phase induced by DTX. AR knockdown enhanced DTX-induced cell apoptosis and cell cycle arrest at the S phase in prostate cancer cells, which was attenuated by FEN1 overexpression. In vivo experiments showed that overexpression of FEN1 significantly increased tumour growth and weakened the inhibitory effect of DTX on prostate tumour growth, while AR knockdown enhance the sensitivity of DTX to prostate tumour. AR knockdown resulted in FEN1, pho-ERK1/2, and pho-ELK1 downregulation, and the luciferase reporter assay confirmed that ELK1 can regulate the transcription of FEN1. CONCLUSION: Collectively, our studies demonstrate that AR knockdown improves the DTX sensitivity of prostate cancer cells by downregulating FEN1 through the ERK/ELK1 signalling pathway.