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1.
Macromol Rapid Commun ; : e2200194, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578790

RESUMO

Despite being the mainstay treatment for many types of cancer in clinic, radiotherapy is undertaking great challenges in overcoming a series of limitations. Radiosensitizers are promising agents capable of depositing irradiation energy and generating free radicals to enhance the radiosensitivity of tumor cells. Combining radiosensitizers with functional polymer-based nanomaterials holds great potential to improve biodistribution, circulation time, and stability in vivo. The derived polymeric nano-radiosensitizers can significantly improve the efficiency of tumor targeting and radiotherapy, and reduce the side effect to healthy tissues. In this review, we provide an overview of functional polymer-based nanomaterials for radiosensitization in recent years. Particular emphases are given to the action mechanisms, drug loading methods, targeting efficiencies, the impact on therapeutic effects and biocompatibility of various radiosensitizing polymers, which are classified as polymeric micelles, dendrimers, polymeric nanospheres, nanoscale coordination polymers, polymersomes, and nanogels. The challenges and outlooks of polymeric nano-radiosensitizers are also discussed. This article is protected by copyright. All rights reserved.

2.
Ann Transl Med ; 10(7): 413, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530951

RESUMO

Background: The pathogenesis of Crohn's disease (CD) is unknown; however, angiogenesis is known to play an important role in the disease. The present research suggests that microRNA-21 (miR-21) may play a positive regulatory role in disordered angiogenesis in CD. Methods: C57 wild-type mice were divided into 6 groups. On day 0, all mice in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) group were given an enema at the concentration of TNBS 100 mg/kg mouse body weight (solvent 50% alcohol). In the control group, the enema was performed with 50% alcohol. On day 0, 2, 4, and 6, the mice of the agomir-21 + TNBS group and the agomir control + TNBS group were injected with 200 µL, 5 nmol agomir-21 or agomir control [dissolved in ribonuclease (RNase)-free water] by tail vein injection, while the antagomir-21 + TNBS group and the antagomir control + TNBS group were injected with 200 µL, 20 nmol antagomir-21 or antagomir control (dissolved in RNase-free water). The body weight and disease activity index (DAI) score were recorded daily. The colons were obtained to assess macro and microscopic colon damage. The inferior vena cava and the accompanying abdominal aorta were chosen to detect the protein expression of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT)/vascular endothelial growth factor (VEGF) axis through western blotting. Serum interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The distribution and expression of neovascularization were demonstrated by cluster of differentiation 31 (CD31) immunohistochemistry. Results: Compared with the only-TNBS group, the agomir-21 + TNBS group showed significantly severer colitis symptoms and more abnormal vascular hyperplasia, while the antagomir-21 + TNBS group showed symptom relief and reduced vascular hyperplasia. In addition, agomir-21 obviously inhibited the expression of PTEN and activated the PI3K/AKT/VEGF pathway in mice induced by TNBS, while antagomir-21 effectively antagonized this effect. Conclusions: miR-21 can promote the progression of colitis in mice induced by TNBS and aggravate the disordered angiogenesis by regulating the PTEN/PI3K/AKT axis. Intravenous injection of miR-21 antagonists can effectively relieve the symptoms of colitis and inhibit colonic angiogenesis.

3.
Nat Commun ; 13(1): 2625, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551194

RESUMO

X-ray computed tomography (CT) has an important role in precision medicine. However, CT contrast agents with high efficiency and the ability to translate diagnostic accuracy into therapeutic intervention are scarce. Here, poly(diiododiacetylene) (PIDA), a conjugated polymer composed of only carbon and iodine atoms, is reported as an efficient CT contrast agent to bridge CT diagnostic imaging with therapeutic intervention. PIDA has a high iodine payload (>84 wt%), and the aggregation of nanofibrous PIDA can further amplify CT intensity and has improved geometrical and positional stability in vivo. Moreover, with a conjugated backbone, PIDA is in deep blue color, making it dually visible by both CT imaging and the naked eyes. The performance of PIDA in CT-guided preoperative planning and visualization-guided surgery is validated using orthotopic xenograft rat models. In addition, PIDA excels clinical fiducial markers of imaging-guided radiotherapy in efficiency and biocompatibility, and exhibits successful guidance of robotic radiotherapy on Beagles, demonstrating clinical potential to translate CT diagnosis accuracy into therapeutic intervention for precision medicine.

4.
Isotopes Environ Health Stud ; : 1-18, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503680

RESUMO

Serving as a medium between source water and cellulose, leaf water contributes to the isotope ratios (δ18O, δ2H) of plant organic matter, which can be used for paleoclimate reconstruction. This study is the first to examine the diurnal variations in the δ18O and δ2H of leaf water on the southern Tibetan Plateau. The δ18O and δ2H of leaf water were relatively low when precipitation events occurred. In particular, 18O and 2H of leaf water became extremely depleted 5 h after the precipitation event. Our findings demonstrate that precipitation can modify the isotope ratios of leaf water from external and internal causes. First, precipitation events affect meteorological elements, lead to decreases in leaf transpiration, and immediately weaken the isotope enrichment of leaf water ('rapid effect' of precipitation). Second, precipitation events affect the internal plant-soil water cycle process, causing the plant to preferentially use deeper soil water, and the corresponding isotope ratios of leaf water exhibit extremely low values 5 h after precipitation events ('delay effect' of precipitation). This study suggests that researchers need to be cautious in separating the signals of precipitation and hydrological processes when interpreting isotope records preserved in tree-ring cellulose archives from the Tibetan Plateau.

5.
NMR Biomed ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488376

RESUMO

Hemifacial spasm (HFS) is characterized by involuntary and paroxysmal muscle contractions on the hemiface. It is generally believed that HFS is caused by neurovascular compression (NVC) at the root exit zone (REZ) of the facial nerve. In recent years, the structural alterations of brains with HFS have aroused growing concern. However, little attention has been directed to possible involvement of specific white matter (WM) tracts and topological properties of structural networks in HFS. In the present study, diffusion magnetic resonance imaging (dMRI) tractography was utilized to construct structural networks and perform tractometric analysis. The diffusion tensor imaging scalar parameters along with the WM tracts, and the topological parameters of global networks and sub-networks were assessed in 62 HFS patients and 57 demographically matched healthy controls (HCs). Moreover, we investigated the correlation of these parameters with disease-clinical-level (DCL) and disease-duration-time (DDT) of HFS patients. Compared with HCs, HFS patients had additional hub regions including the amygdala, ventromedial putamen, lateral occipital cortex, and rostral cuneus gyrus. Furthermore, HFS patients showed significant alternations with specific topological properties in some structural sub-networks including limbic, default mode, dorsal attention, somato-motor, and control network, as well as diffusion properties in some WM tracts including superior longitudinal fasciculus, cingulum bundle, thalamo-frontal, and corpus callosum. These sub-networks and tracts were associated with the regulation of emotion, motor, vision, and attention. Notably, we also found that the parameters with sub-networks and tracts exhibited correlation with DCL and DDT. In addition to corroborating previous findings in HFS, this study demonstrated the changed microstructures in specific locations along with the fiber tracts and changed topological properties in structural sub-networks.

6.
Int J Med Sci ; 19(3): 416-424, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370471

RESUMO

Loss of renal function may render hemodialysis patients more susceptible to infectious diseases, which is the second of all-causes mortality in this population. In addition to infection caused by the classic Klebsiella pneumoniae (cKp), however, hemodialysis staffs are now facing new challenge with growing prevalence of the carbapenem-resistant Kp (CR-Kp) and hypervirulent Kp (hvKp) as they are respectively associated with increased drug-resistance and virulence. We therefore chose to share our recent experience in treating severe infections either caused (cKp, CR-Kp, hvKp) or complicated (CR-hvKp) by these strains in hemodialysis patients. Based upon yet beyond published works, we further came up with the detection of intracranial lesion, novel diagnostic approach using unique biomarkers followed by selection of appropriate antibiotics, management of metastasic abscesses and bracing for the most lethal scenario in the order of cKp, CR-Kp, hvKp and CR-hvKp, respectively. Since reports of complicated hvKp infection in hemodialysis patients were rare, we also discussed in details this clinical entity focusing on its epidemiology, mechanism of increased virulence and involvement of the arteriovenous fistula as insidious source of persistent septicemia. By covering the full spectrum of clinically relevant Kp stains specifically from the viewpoint of nephrology, our work had highlighted the importance of infection control in uremic state and vice versa. As such, it may greatly raise the awareness of dialysis staffs against the challenge of evolving Klebsiella pneumoniae infection in hemodialysis patients and expeditiously reach a higher degree of readiness which was proved to be the key determinant of ultimate survival.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Diálise Renal/efeitos adversos , Virulência
7.
Vet Sci ; 9(4)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35448688

RESUMO

The porcine interferon (PoIFN) complex represents an ideal model for studying IFN evolution which has resulted from viral pressure during domestication. Bama and Banna miniature pigs are the two Chinese miniature pig breeds that have been developed as laboratory animal models for studying virus infection, pathogenesis, and vaccine evaluation. However, the PoIFN complex of such miniature pig breeds remains to be studied. In the present study, we cloned PoIFN-ß genes from Bama and Banna miniature pigs, detected their PoIFN-ß tissue expression profiles, prepared recombinant PoIFN-ß (rPoIFN-ß) using the E. coli expression system, and measured their antiviral activities against three different pig viruses. At the amino acid sequence level, PoIFN-ßs of the two miniature pig breeds were identical, which shared 100% identity with that of Congjiang Xiang pigs, 99.4-100% identity with that of domestic pigs, and 99.5% identity with that of three species of African wild boars. The tissue expression profiles of PoIFN-ß mRNA differed not only between the two miniature pig breeds but between miniature pigs and domestic pigs as well. The four promoter domains of PoIFN-ß of the two miniature pig breeds were identical with that of humans, domestic pigs, and three species of African wild boars. The recombinant PoIFN-ß prepared from the two miniature pig breeds showed dose-dependent pre-infection and post-infection antiviral activities against vesicular stomatitis virus, porcine respiratory and reproductive syndrome virus, and pig pseudorabies virus. This study provided evidence for the high sequence conservation of PoIFN-ß genes within the Suidae family with different tissue expression profiles and antiviral activities.

8.
Ann Transl Med ; 10(5): 258, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35402577

RESUMO

Background: Angiogenesis and vascular dysfunction play important roles in the occurrence and development of Crohn's disease (CD), but relevant mechanistic research is lacking. This paper aimed to use exosomal technology to elucidate the mechanism of vascular abnormalities in CD. Methods: Ultra-high-speed centrifugation was used to extract circulating exosomes. Electron microscopy, particle size, and biomarker detection were used for exome quality control. MicroRNA 21 (miR-21) levels were determined by quantitative polymerase chain reaction (qPCR). Migration abilities and tubule-forming capacity were assessed by wound healing assay, transwell invasion test, and tube formation assay. Exosome biomarkers and pathway protein levels were determined by western blotting. Results: Our data revealed that the circulating exosomes of patients with CD have a remarkable effect on the proliferation and migration of human umbilical vein endothelial cells (HUVECs), and that exosomal miR-21 levels were highly elevated in exosomes derived from the plasma of CD patients. Exosomes derived from CD patients and miR-21 mimic had more powerful migration abilities and tubule-forming capacity than control groups. miR-21 inhibitors significantly blocked the quick migration and tubule formation of HUVECs induced by CD-exosomes. Western blot analysis revealed that circulating exosome miR-21 in HUVECs might weaken negative regulation of phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) by target-inhibiting phosphatase and tensin homolog (PTEN) and inducing the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusions: Circulating exosomal miR-21 mediates HUVEC proliferation and migration through PTEN/PI3K/AKT in CD. Exosomal miR-21 may be a new biomarker or therapeutic target for the treatment of vascular abnormalities in CD.

9.
J Immunother Cancer ; 10(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35483745

RESUMO

BACKGROUND: Anti-GD2 monoclonal antibody immunotherapy has significantly improved the overall survival rate for high-risk neuroblastoma patients. However, 40% of patients fail to respond or develop resistance to treatment, and the molecular mechanisms by which this occurs remain poorly understood. Tumor-derived small extracellular vesicles (sEVs) have emerged as critical regulators in modulating the response to immunotherapy. In this study, we investigated the role of neuroblastoma-derived sEVs in promoting resistance to the anti-GD2 monoclonal antibody dinutuximab. Moreover, to determine whether pharmacologic inhibition of sEV secretion sensitizes tumors to dinutuximab treatment, we combined dinutuximab with tipifarnib, a farnesyltransferase inhibitor that inhibits sEV secretion. METHODS: We investigated the role of neuroblastoma-derived sEVs in modulating the response to dinutuximab by utilizing the syngeneic 9464D-GD2 mouse model. The effect of neuroblastoma-derived sEVs in modulating the tumor microenvironment (TME) and host immune system were evaluated by RNA-sequencing and flow cytometry. Importantly, we used this mouse model to investigate the efficacy of tipifarnib in sensitizing neuroblastoma tumors to dinutuximab. The effect of tipifarnib on both the TME and host immune system were assessed by flow cytometry. RESULTS: We demonstrated that neuroblastoma-derived sEVs significantly attenuated the efficacy of dinutuximab in vivo and modulated tumor immune cell infiltration upon dinutuximab treatment to create an immunosuppressive TME that contains more tumor-associated macrophages and fewer tumor-infiltrating NK cells. In addition, we demonstrated that neuroblastoma-derived sEVs suppress splenic NK cell maturation in vivo and dinutuximab-induced NK cell-mediated antibody-dependent cellular cytotoxicity in vitro. Importantly, tipifarnib drastically enhanced the efficacy of dinutuximab-mediated inhibition of tumor growth and prevented the immunosuppressive effects of neuroblastoma-derived sEVs in vivo. CONCLUSIONS: These preclinical findings uncover a novel mechanism by which neuroblastoma-derived sEVs modulate the immune system to promote resistance to dinutuximab and suggest that tipifarnib-mediated inhibition of sEV secretion may serve as a viable treatment strategy to enhance the antitumor efficacy of anti-GD2 immunotherapy in high-risk neuroblastoma patients.


Assuntos
Antineoplásicos , Vesículas Extracelulares , Neuroblastoma , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Camundongos , Neuroblastoma/patologia , Quinolonas , Microambiente Tumoral
10.
BMC Med Genomics ; 15(Suppl 2): 94, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461273

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNA that can downregulate their targets by selectively binding to the 3' untranslated region (3'UTR) of most messenger RNAs (mRNAs) in the human genome. MiRNAs can interact with other molecules such as viruses and act as a mediator for viral infection. In this study, we examined whether, and to what extent, the SARS-CoV-2 virus can serve as a "sponge" for human miRNAs. RESULTS: We identified multiple potential miRNA/target pairs that may be disrupted during SARS-CoV-2 infection. Using miRNA expression profiles and RNA-seq from published studies, we further identified a highly confident list of 5 miRNA/target pairs that could be disrupted by the virus's miRNA sponge effect, namely hsa-miR-374a-5p/APOL6, hsa-let-7f-1-3p/EIF4A2, hsa-miR-374a-3p/PARP11, hsa-miR-548d-3p/PSMA2 and hsa-miR-23b-3p/ZNFX1 pairs. Using single-cell RNA-sequencing based data, we identified two important miRNAs, hsa-miR-302c-5p and hsa-miR-16-5p, to be potential virus targeting miRNAs across multiple cell types from bronchoalveolar lavage fluid samples. We further validated some of our findings using miRNA and gene enrichment analyses and the results confirmed with findings from previous studies that some of these identified miRNA/target pairs are involved in ACE2 receptor network, regulating pro-inflammatory cytokines and in immune cell maturation and differentiation. CONCLUSION: Using publicly available databases and patient-related expression data, we found that acting as a "miRNA sponge" could be one explanation for SARS-CoV-2-mediated pathophysiological changes. This study provides a novel way of utilizing SARS-CoV-2 related data, with bioinformatics approaches, to help us better understand the etiology of the disease and its differential manifestation across individuals.


Assuntos
COVID-19 , MicroRNAs , SARS-CoV-2 , Regiões 3' não Traduzidas , COVID-19/genética , Biologia Computacional/métodos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
11.
J Cell Mol Med ; 26(9): 2594-2606, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35366055

RESUMO

This study was performed to uncover the effects of dexmedetomidine on oxidative stress injury induced by mitochondrial localization of telomerase reverse transcriptase (TERT) in enteric glial cells (EGCs) following intestinal ischaemia-reperfusion injury (IRI) in rat models. Following establishment of intestinal IRI models by superior mesenteric artery occlusion in Wistar rats, the expression and distribution patterns of TERT were detected. The IRI rats were subsequently treated with low or high doses of dexmedetomidine, followed by detection of ROS, MDA and GSH levels. Calcein cobalt and rhodamine 123 staining were also carried out to detect mitochondrial permeability transition pore (MPTP) and the mitochondrial membrane potential (MMP), respectively. Moreover, oxidative injury of mtDNA was determined, in addition to analyses of EGC viability and apoptosis. Intestinal tissues and mitochondria of EGCs were badly damaged in the intestinal IRI group. In addition, there was a reduction in mitochondrial localization of TERT, oxidative stress, whilst apoptosis of EGCs was increased and proliferation was decreased. On the other hand, administration of dexmedetomidine was associated with promotion of mitochondrial localization of TERT, whilst oxidative stress, MPTP and mtDNA in EGCs, and EGC apoptosis were all inhibited, and the MMP and EGC viability were both increased. A positive correlation was observed between different doses of dexmedetomidine and protective effects. Collectively, our findings highlighted the antioxidative effects of dexmedetomidine on EGCs following intestinal IRI, as dexmedetomidine alleviated mitochondrial damage by enhancing the mitochondrial localization of TERT.


Assuntos
Dexmedetomidina , Traumatismo por Reperfusão , Telomerase/metabolismo , Animais , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Dexmedetomidina/farmacologia , Metaloproteinases da Matriz/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Neuroglia/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
12.
Proteomics ; : e2100320, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35388624

RESUMO

Pancreatic cancer is a lethal malignancy and no screening biomarker or targeted therapy is currently available. Here, we performed a shotgun proteomic label-free quantification (LFQ) to define protein changes in the cellular proteome and secretome of four pancreatic cancer cell lines (PANC1, Paca44, Paca2, and BXPC3) versus normal human pancreatic ductal epithelial cells (HPDE). In the cellular proteome and secretome, 149 and 43 proteins were dysregulated in the most cancer cell lines, respectively. Using Ingenuity Pathway Analysis (IPA), the most dysregulated signaling pathways in pancreatic cancer cells included the activation of epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular regulated kinase (ERK), and the deactivation of type-I interferon (IFN) pathways, which could promote cancer cell progression and decrease antitumor immunity. Parallel reaction monitoring (PRM) mass spectrometry was used to confirm the changes of seven regulated proteins quantified by LFQ: EGFR, growth/differentiation factor 15 (GDF15), protein-glutamine gamma-glutamyltransferase 2 (TGM2), leukemia inhibitory factor (LIF), interferon-induced GTP-binding protein Mx1 (MX1), signal transducer and activator of transcription 1 (STAT1), and serpin B5 (SERPINB5). Together, this proteomic analysis highlights protein changes associated with pancreatic cancer cells that should be further investigated as potential biomarkers or therapeutic targets.

13.
Toxicology ; 470: 153152, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35288261

RESUMO

Silicosis is caused by the continuous inhalation of environmental silica dust. The repetitive exposure of silica induces airway epithelial cell injury, leads proliferative exhaustion of epithelial stem cells, ultimately results in the lung remodeling and the development of silicosis. The B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a pivotal transcription factor in stem cell self-renewal and proliferation of many tissues including the lung, but its role in the airway basal cell proliferation and differentiation during the pathogenesis of silicosis in lung has yet been investigated. In this study, the function of Bmi1 in airway basal cell proliferation and differentiation in response to silica challenge was investigated in lungs of silicosis mice and primary human bronchial epithelia cells (HBECs) exposed to silica dioxide (SiO2). Results showed a decreased expression of Bmi1 protein, epithelial basal cell markers Krt14 and Krt5, club cell marker Clara cell secretory protein, and ciliated cell marker acetyl-α-tubulin in silicosis lungs, compared to healthy mice. In consistence, a persistent exposure of SiO2 reduced the capacity of cell proliferation and differentiation in HBECs, as ascertained by the reduction of differentiated epithelial cell markers and BMI1 expression, while an increased P21-positive senescent cell fraction. Moreover, an overexpression of BMI1 in HBECs reduced the SiO2-senescent cells, enhanced the potency of cell proliferation and differentiation, and increased capacity of airway epithelial regeneration in response to the persistent exposure of SiO2. These data suggest that Bmi1 is a key transcription factor engaging in maintaining the self-renewal, proliferation and differentiation of epithelial stem cells in lung during the development of silicosis disease.


Assuntos
Dióxido de Silício , Silicose , Animais , Células Epiteliais/metabolismo , Pulmão/patologia , Camundongos , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Dióxido de Silício/metabolismo , Dióxido de Silício/toxicidade , Silicose/patologia
14.
Front Neurol ; 13: 845926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295828

RESUMO

Objective: The therapeutic effect of deep brain stimulation (DBS) surgery mainly depends on the accuracy of electrode placement and the reduction in brain shift. Among the standard procedures, cerebrospinal fluid (CSF) loss or pneumocephalus caused by dura incision (DI) is thought to be the main reason for brain shift and inaccuracy of electrode placement. In the current study, we described a modified dura puncture (DP) procedure to reduce brain shift and compare it with the general procedure of DBS surgery in terms of electrode placement accuracy. Materials and Methods: We retrospectively analyzed a series of 132 patients who underwent DBS surgery in Wuhan Union Hospital from December 2015 to April 2021. According to the different surgery procedures, patients were classified into two cohorts: the DI group (DI cohort) had 49 patients who receive the general procedure, and the DP group (DP cohort) had 83 patients who receive the modified procedure. Postoperative pneumocephalus volume (PPV) and CSF loss volume, electrode fusion error (EFE), and trajectory number were calculated. Meanwhile, intraoperative electrophysiological signal length (IESL), electrode implantation duration, and other parameters were analyzed. Results: In the current study, we introduced an improved electrode implantation procedure for DBS surgery named the DP procedure. Compared with the general DI cohort (n = 49), the modified DP cohort (n = 83) had a shorter electrode implantation duration (p < 0.0001), smaller PPV, lower CSF leakage volume (p < 0.0001), and smaller EFE (p < 0.0001). There was no significant difference in IESL (p > 0.05) or adverse events (perioperative cerebral haematoma, skin erosion, epilepsy, p > 0.05) between the two cohorts. Conclusion: The DP procedure is a modified procedure that can reduce brain shift and ensure implantation accuracy during DBS surgery without adverse events.

15.
Front Oncol ; 12: 841179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296004

RESUMO

Objective: T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL. Methods: We analyzed the outcomes for 105 consecutive patients treated using the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study. Results: The 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values < 0.01). Conclusion: The CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.

16.
Ecotoxicol Environ Saf ; 234: 113414, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35305350

RESUMO

Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) has a long coevolutionary history with its host, exerting profound effects on larval development, physiology and immune responses, although the mechanisms mediating these effects remain unclear. We demonstrate that HearNPV infection constrains the growth and development of larvae by inducing high levels of reactive oxygen species (ROS), which increase the expression of forkhead box O transcription factor (FoxO). FoxO upregulates the expression of peroxiredoxin 1 (Prx1) which serves to regulate larval development and immune responses following HearNPV infection. Collectively, our results provide novel insights into the role of Prx1 in larval development and immunity subsequent to HearNPV infection. Further investigation of the oxidative stress induced by HearNPV in H. armigera and its interactions with host immunity could yield novel insights useful in agricultural pest control.

17.
Mol Ecol ; 31(9): 2752-2765, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35258140

RESUMO

Baculoviruses can induce climbing behaviour in their caterpillar hosts to ensure they die at elevated positions to enhance virus transmission, providing an excellent model to study parasitic manipulation of host behaviour. Here, we demonstrate that climbing behaviour occurred mostly during daylight hours, and that the height at death of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV)-infected larvae increases with the height of the light source. Phototaxic and electroretinogram (ERG) responses were enhanced after HearNPV-infection in host larvae, and ablation of stemmata in infected larvae prevented both phototaxis and climbing behaviour. Through transcriptome and quantitative PCR, we confirmed that two opsin genes (a blue light-sensitive gene, HaBL; and a long wave-sensitive gene, HaLW) as well as the TRPL (transient receptor potential-like channel protein) gene, all integral to the host's visual perception pathway, were significantly upregulated after HearNPV infection. Knockout of HaBL, HaLW, or TRPL genes using the CRISPR/Cas9 system resulted in significantly reduced ERG responses, phototaxis, and climbing behaviour in HearNPV-infected larvae. These results reveal that HearNPV alters the expression of specific genes to hijack host visual perception at fundamental levels-photoreception and phototransduction-in order to induce climbing behaviour in host larvae.


Assuntos
Lepidópteros , Nucleopoliedrovírus , Animais , Baculoviridae , Larva/genética , Lepidópteros/fisiologia , Nucleopoliedrovírus/genética , Percepção Visual
18.
Biomater Sci ; 10(9): 2215-2223, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35322266

RESUMO

Indirubin is considered to have promising potential in the treatment of ulcerative colitis (UC). However, poor aqueous solubility and low bioavailability limit its clinical application. We produced indirubin-loaded bovine serum albumin nanoparticles (INPs) and characterized their drug encapsulation efficiency, drug-loading capacity, capacity to release indirubin in vitro and short-term physical stability. We also investigated the pharmacokinetics of INPs in mice. We then compared the curative effects of INPs and indirubin against dextran sulfate sodium-induced colitis in mice and 3D cultured biopsies from patients with UC. In the mouse model, the outcomes of INP treatment, including the disease activity index and serous levels of interleukin (IL)-1ß and IL-10, were significantly different from those of indirubin treatment. Similarly, when we administered INPs and indirubin to the ex vivo colonic tissues of patients with UC, the effect of INPs was stronger than that of indirubin for most antioxidant and anti-inflammatory biomarkers. The results of both the animal trial and ex vivo experiment indicate that the therapeutic effect of indirubin was further enhanced by the carrier system, making it a highly promising medical candidate for UC.


Assuntos
Colite Ulcerativa , Animais , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Humanos , Indóis , Camundongos , Camundongos Endogâmicos BALB C , Soroalbumina Bovina
19.
J Safety Res ; 80: 330-340, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35249613

RESUMO

INTRODUCTION: As China has recently lifted the age limit for getting access to driving licenses, older drivers' safety issues have received wide attention. Driving self-regulation can be regarded as an adjustment strategy for older adults to reduce risks and extend driving lives. Studies abroad mainly stress the three levels and influencing factors of driving self-regulation. China has a long history with a unique cultural background and social reality and relevant research are still in the initial stage. METHOD: This study applied the extended Theory of Planned Behavior (TPB) to explore the psychological factors that affected self-regulation of older drivers. 317 participants mainly from Beijing urban area completed the questionnaires including demographic information and extend TPB items. RESULTS: Bivariate correlation analysis showed that self-regulation was negatively correlated with the amount of driving experience (days per week and mileages per month) in a significant way. And so was the number of family-owned motor vehicles. Exploratory factor analysis indicated that the extended TPB questionnaire was reliable and effective for measuring self-regulation. The proposed Structural Equation Model (SEM) explained 73.673% of the variance in self-regulation intention. Attitude (0.50) had the strongest influence among all variables on intention. Subjective norms (0.28), perceived behavior control (0.27), and alternative traffic quality (0.20) significantly influenced intention. Intention (0.34) and physical condition (0.22) imposed significant effect on self-regulation behavior. Practical applications: Feasible suggestions were put forward that contribute to self-regulate reasonably. This study helps to better understand the nature of self-regulation behaviors and provides a theoretical basis for formulating scientific intervention measures. On the transportation side, people from all communities of society should care for and support older drivers.


Assuntos
Condução de Veículo , Autocontrole , Idoso , Atitude , Condução de Veículo/psicologia , Humanos , Intenção , Veículos Automotores , Inquéritos e Questionários
20.
Front Immunol ; 13: 805558, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280986

RESUMO

Virus-induced asthma exacerbation is a health burden worldwide and lacks effective treatment. To better understand the disease pathogenesis and find novel therapeutic targets, we established a mouse model of steroid (dexamethasone (DEX)) resistant asthma exacerbation using ovalbumin (OVA) and influenza virus (FLU) infection. Using liquid chromatography-tandem mass spectrometry (LC-MC/MS), we performed a shotgun proteomics assay coupled with label-free quantification to define all dysregulated proteins in the lung proteome of asthmatic mice. Compared to control, 71, 89, and 30 proteins were found significantly upregulated by at least two-fold (p-value ≤ 0.05) in OVA-, OVA/FLU-, and OVA/FLU/DEX-treated mice, respectively. We then applied a Z-score transformed hierarchical clustering analysis and Ingenuity Pathway Analysis (IPA) to highlight the key inflammation pathways underlying the disease. Within all these upregulated proteins, 64 proteins were uniquely highly expressed in OVA/FLU mice compared to OVA mice; and 11 proteins were DEX-refractory. IPA assay revealed two of the most enriched pathways associated with these over-expressed protein clusters were those associated with MHC class I (MHC-I) antigen-presentation and interferon (IFN) signaling. Within these pathways, signal-transducer-and-activator-of-transcription-1 (STAT1) protein was identified as the most significantly changed protein contributing to the pathogenesis of exacerbation and the underlying steroid resistance based on the label-free quantification; and this was further confirmed by both Parallel Reaction Monitoring (PRM) proteomics assay and western blots. Further, the pharmacological drug Fludarabine decreased STAT1 expression, restored the responsiveness of OVA/FLU mice to DEX and markedly suppressed disease severity. Taken together, this study describes the proteomic profile underpinning molecular mechanisms of FLU-induced asthma exacerbation and identifies STAT1 as a potential therapeutic target, more importantly, we provided a novel therapeutic strategy that may be clinically translated into practice.


Assuntos
Asma , Proteômica , Animais , Asma/metabolismo , Citocinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Esteroides/uso terapêutico , Vidarabina/análogos & derivados
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