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1.
Cell Res ; 33(12): 923-939, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37932447

RESUMO

Combination therapy with PD-1 blockade and IL-2 substantially improves anti-tumor efficacy comparing to monotherapy. The underlying mechanisms responsible for the synergistic effects of the combination therapy remain enigmatic. Here we show that PD-1 ligation results in BATF-dependent transcriptional induction of the membrane-associated E3 ubiquitin ligase MARCH5, which mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γc). PD-1 ligation also activates SHP2, which dephosphorylates γcY357, leading to impairment of γc family cytokine-triggered signaling. Conversely, PD-1 blockade restores γc level and activity, thereby sensitizing CD8+ T cells to IL-2. We also identified Pitavastatin Calcium as an inhibitor of MARCH5, which combined with PD-1 blockade and IL-2 significantly improves the efficacy of anti-tumor immunotherapy in mice. Our findings uncover the mechanisms by which PD-1 signaling antagonizes γc family cytokine-triggered immune activation and demonstrate that the underlying mechanisms can be exploited for increased efficacy of combination immunotherapy of cancer.


Assuntos
Inibidores de Checkpoint Imunológico , Subunidade gama Comum de Receptores de Interleucina , Neoplasias , Receptor de Morte Celular Programada 1 , Animais , Camundongos , Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Interleucina-2 , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Membrana/metabolismo
2.
Zhonghua Nan Ke Xue ; 29(1): 83-87, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-37846838

RESUMO

OBJECTIVE: To investigate the clinical effect of dumai (governor meridian) moxibustion combined with low-dose tadalafil in the treatment of ED with decline of vital gate fire. METHODS: We enrolled in this study 130 ED patients with decline of vital gate fire who met the inclusion criteria and equally randomized them into a control and an experimental group, the former treated with low-dose tadalafil tablets at 5 mg once a day while the latter by dumai moxibustion once a week in addition, all for 4 weeks. Of the total number of subjects, 62 in the control group and 63 in the experimental group completed the experiment. We recorded the scores on IIEF-5, Erection Quality Scale (EQS), Erection Hardness Scale (EHS), TCM symptoms and Treatment Satisfaction Scale (TSS) as well as the penile hemodynamic parameters peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) before and after treatment and compared them between the two groups. RESULTS: The total response rate was significantly higher in the experimental group than in the control (87.30% vs 66.13%, P < 0.05). IIEF-5, EQS, EHS and TSS scores, PSV and RI were markedly increased while TCM symptoms and EDV remarkably decreased in both groups after treatment (P < 0.05), even more significantly in the experimental than in the control group (P < 0.05). CONCLUSION: Dumai moxibustion combined with low-dose tadalafil can improve erectile function, increase penile blood flow velocity and alleviate clinical symptoms in ED patients with decline of vital gate fire, with definite clinical effect and safety.


Assuntos
Disfunção Erétil , Moxibustão , Masculino , Humanos , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/diagnóstico , Tadalafila/uso terapêutico , Tadalafila/farmacologia , Ereção Peniana , Pênis , Resultado do Tratamento , Carbolinas/uso terapêutico , Carbolinas/farmacologia
3.
Yi Chuan ; 45(10): 922-932, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37872114

RESUMO

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.


Assuntos
Genoma , Modelos Genéticos , Suínos/genética , Animais , Fenótipo , Genômica/métodos , Genótipo , Polimorfismo de Nucleotídeo Único
4.
Biosens Bioelectron ; 241: 115686, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37729810

RESUMO

Micro/nanomotors (MNMs) emerge as a vital candidate for biosensing due to its nano-size structure, high surface-to-area ratio, directional mobility, biocompatibility, and ease of functionalization, therefore being able to detect objects with high efficiency, precision, and selectivity. The driving mode, nanostructure, materials property, preparation technique, and biosensing applications have been thoroughly discussed in publications. To promote the MNMs-based biosensors from in vitro to in vivo, it is necessary to give a comprehensive discussion from the perspective of sensing performances enhancement. However, until now, there is few reviews dedicated to the systematic discussion on the multiple performance enhancement schemes and the current challenges of MNMs-based biosensors. Bearing it in mind and based on our research experience in this field, we summarized the enhancement methods for biosensing properties such as sensitivity, selectivity, detection time, biocompatibility, simplify system operation, and environmental availability. We hope that this review provides the readers with fundamental understanding on performance enhancement schemes for MNMs-based biosensors.

5.
ACS Sens ; 8(10): 3862-3872, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37752695

RESUMO

In this work, a new type, highly sensitive, and reusable nanoplastics (NPs) microwave detection method is proposed, which can be used to rapidly analyze NPs with different surface charges and sizes. The effective dielectric constant of NPs varies according to the different concentrations, particle sizes, and surface charges of NPs in aqueous solution. The feasibility of the microwave method for differential-charged NPs detection is verified using a complementary split ring resonator sensor manufactured on a cost-effective printed circuit board, which shows a high sensitivity only for positively charged NPs (PS-NH2) detection. To achieve microwave detection of both positively and negatively charged NPs (PS-SO3H), a microscale spiral-coupled resonator sensing chip is manufactured through integrated passive technology, which demonstrates extremely low detection limits and high sensitivity for both PS-NH2 and PS-SO3H, with different concentrations, particle sizes, and charges. In addition, for NPs solution doped with methyl orange, the device can still perform stable measurements, overcoming the inability of traditional NPs molecular element determination and optical detection methods to detect NPs aqueous solution with organic matter doping and color presence. The proposed microwave detection method could also be extended to sensing detection for detecting other hazardous environmental substances.


Assuntos
Microplásticos , Micro-Ondas
6.
Chem Commun (Camb) ; 59(39): 5850-5853, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37098687

RESUMO

Octameric Aep1 was employed, for the first time to the best of our knowledge, as a nanopore to expand applications. After investigating the optimized conditions of Aep1 for single-channel recording, the sensing features were characterized. Cyclic and linear molecules of varying sizes and charges were employed to probe the radius and chemical environment of the pore, providing deep insights for expected future endeavors at predicting the structure of octameric Aep1. γ-CD showed unique suitability as an 8-subunit adapter in octameric Aep1, enabling the discrimination of ß-nicotinamide mononucleotide.


Assuntos
Toxinas Bacterianas , Nanoporos , Proteínas , Toxinas Bacterianas/química , Proteínas Citotóxicas Formadoras de Poros/química
7.
World J Gastrointest Oncol ; 15(2): 240-250, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36908324

RESUMO

The advent of immunotherapy and the development of immune checkpoint inhibitors (ICIs) are changing the way we think about cancer treatment. ICIs have shown clinical benefits in a variety of tumor types, and ICI-based immunotherapy has shown effective clinical outcomes in immunologically "hot" tumors. However, for immunologically "cold" tumors such as colorectal cancer (CRC), only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates. In this review, we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC, and summarize the treatment strategies and challenges of immunotherapy for cold CRC. We also explain the mechanism, biology, and role of immunotherapy for cold CRC, which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.

8.
Trends Hear ; 27: 23312165221148846, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632674

RESUMO

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.


Assuntos
Implante Coclear , Implantes Cocleares , Auxiliares de Audição , Perda Auditiva Neurossensorial , Criança , Humanos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/terapia , Limiar Auditivo/fisiologia
9.
Angew Chem Int Ed Engl ; 61(44): e202209970, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36083823

RESUMO

Accurate discrimination of amyloid-ß (Aß) peptides containing familial point mutations would advance the knowledge of their roles in early-onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild-type (WT) Aß18-26 peptides with aerolysin nanopore using a 3D blockage mapping strategy. The standard deviation of current blockade fluctuations (σb ) was proposed as a new supplement to current blockage (Ib /I0 ) and duration time (tD ) to profile the blockage characteristics of single molecules. Although the WT and A21G Aß18-26 are indistinguishable in a traditional Ib /I0 -tD 2D description, ∼87 % of the blockade events can be accurately classified with half reduction of false identification using a combination of Ib /I0 , tD, and σb . This work offers an easy and reliable strategy to promote nanopore sensitivity of peptide mutants, leading to a more precise analysis of pathogenic mutations for developing effective diagnosis and treatment.


Assuntos
Doença de Alzheimer , Nanoporos , Humanos , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/química , Mutação Puntual , Doença de Alzheimer/genética , Mutação , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/química
10.
Clin Respir J ; 16(4): 309-316, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35229474

RESUMO

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a new technique to obtain specimens for diagnosis of interstitial lung disease (ILD) in recent years. The objective of this study is to evaluate the safety and the diagnostic accuracy of TBLC in patients of desquamative interstitial pneumonia (DIP). METHODS: In this study twelve patients confirmed with DIP were selected from January 2019 to December 2020 at the department of pulmonary and critical care medicine in China-Japan Friendship Hospital. All cases underwent TBLC in a hybrid cone beam CT (CBCT) operation room with a single general anesthesia. The definitive diagnosis was made by a multidisciplinary team that involved clinicians, radiologists and pathologists. This study analyzed the biopsy sample surface areas, main complications and the consistency between TBLC pathology and multidisciplinary discussion (MDD) diagnosis for DIP. RESULTS: An average of 3.1 ± 1.1 specimens were obtained per patient. The mean surface area of the specimen was 23.7 ± 6.1 mm2 . None of the cases had pneumothorax or massive hemorrhage. Ten cases (83.3%) had no or mild bleeding and two cases (16.7%) had moderate bleeding. All cases had the typical pathologic characteristics of DIP, which was highly consistent with the diagnosis of MDD. CONCLUSION: TBLC can obtain sufficient samples for the pathological diagnosis of DIP, which has high security and accuracy in experienced specialist centers.


Assuntos
Doenças Pulmonares Intersticiais , Pneumotórax , Biópsia/efeitos adversos , Biópsia/métodos , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Hemorragia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Pneumotórax/diagnóstico , Pneumotórax/patologia
11.
Langmuir ; 38(3): 1188-1193, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35019652

RESUMO

A biological nanopore is one of the predominant single-molecule approaches as a result of its controllable single-biomolecule interface, which could reflect the "intrinsic" information on an individual molecule in a label-free way. Because the current blockage is normally treated as the most important parameter for nanopore identification of every single molecule, the fluctuation of current blockage for certain types of molecules, defined as full width at half maximum (fwhm) of current blockage, actually owns a dominant influence on nanopore resolution. Therefore, controlling the fwhm of current blockage of molecules is critical for the sensing capability of the nanopore. Here, taking an aerolysin nanopore as a model, by precisely controlling the functional group in this single-biomolecule interface, we could narrow the fwhm of nanopore current blockage for DNA identification and prolong the duration inside the nanopore. Moreover, a substantial correlation between fwhm of current blockage and duration is established, showing a non-monotonic variation. Besides, the mechanism is also clarified with studying the detailed current blockage events. This proposed correlation is further demonstrated to be applied uniformly across different mutant aerolysins for a certain DNA. This study proposes a new strategy for regulating molecular sensing from the duration of the analyte, which could guide the resolution of heterogeneity analysis using nanopores.


Assuntos
Nanoporos , DNA/genética , Nanotecnologia
12.
World J Clin Cases ; 10(1): 296-303, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35071531

RESUMO

BACKGROUND: Primary intracranial alveolar soft-part sarcoma (PIASPS) is a rare malignancy. We aimed to investigate the clinical profiles and outcomes for PIASPS. CASE SUMMARY: We firstly reported five consecutive cases from our institute. Then, the cases from previous studies were pooled and analyzed to delineate the characteristics of this disease. Our cohort included two males and three females. The median age was 21-years-old (range: 8-54-years-old). All the patients received surgical treatment. Gross total resection (GTR), radiotherapy, and chemotherapy were administered in 3 patients, 4 patients, and 1 patient, respectively. After a median follow-up of 36 mo, tumor progression was noticed in 4 patients; and 3 patients died of the disease. Pooled data (n = 14) contained 5 males and 9 females with a median age of 19 years. The log-rank tests showed that GTR (P = 0.011) could prolong progression-free survival, and radiotherapy (P < 0.001) resulted in longer overall survival. CONCLUSION: Patients with PIASPS suffer from poor outcomes. Surgical treatment is the first choice, and GTR should be achieved when the tumor is feasible. Patients with PIASPS benefit from radiotherapy, which should be considered as a part of treatment therapies.

13.
Biosensors (Basel) ; 11(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34940265

RESUMO

In this study, we propose a high-performance resonator-based biosensor for mediator-free glucose identification. The biosensor is characterized by an air-bridge capacitor and fabricated via integrated passive device technology on gallium arsenide (GaAs) substrate. The exterior design of the structure is a spiral inductor with the air-bridge providing a sensitive surface, whereas the internal capacitor improves indicator performance. The sensing relies on repolarization and rearrangement of surface molecules, which are excited by the dropped sample at the microcosmic level, and the resonance performance variation corresponds to the difference in glucose concentration at the macroscopic level. The air-bridge capacitor in the modeled RLC circuit serves as a bio-recognition element to glucose concentration (εglucoseC0), generating resonant frequency shifts at 0.874 GHz and 1.244 GHz for concentrations of 25 mg/dL and 300 mg/dL compared to DI water, respectively. The proposed biosensor exhibits excellent sensitivity at 1.38 MHz per mg/dL with a wide detection range for glucose concentrations of 25-300 mg/dL and a low detection limit of 24.59 mg/dL. Additionally, the frequency shift and concentration are highly linear with a coefficient of determination of 0.98823. The response time is less than 3 s. We performed multiple experiments to verify that the surface morphology reveals no deterioration and chemical binding, thus validating the reusability and reliability of the proposed biosensor.


Assuntos
Técnicas Biossensoriais , Glucose , Micro-Ondas , Reprodutibilidade dos Testes , Tecnologia
14.
Int J Pediatr Otorhinolaryngol ; 148: 110821, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34225082

RESUMO

OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem responses (eABRs) to electrical stimulation at the round window niche (RWN) and round window membrane (RWM) and the effect of deafness duration on functions of the auditory pathway to the level of the brainstem. METHODS: According to the age at cochlear implantation (CI), 99 children with profound sensorineural hearing loss were divided into four groups: ≤12 months (group A), 13-36 months (group B), 37-60 months (group C) and >60 months (group D). The eABRs were evoked by electrical stimulation at RWN and RWM during the operation of CI. RESULTS: The higher eABR extraction rate and lower threshold for RWM stimulation was found than those for RWN stimulation. The eⅢ latencies and eⅢ-eⅤ latency intervals for RWM stimulation were similar among four groups. However, children with earlier CI (group A) showed a significantly shorter eⅤ latency than others. CONCLUSION: The eABR evoked by the electrical stimulation at RWM is more stable and sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway. Development in the upper brainstem pathway may be more vulnerable to long-term deafness as revealed by the eⅤ latency.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Limiar Auditivo , Criança , Estimulação Elétrica , Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/terapia , Humanos
15.
Acta Otolaryngol ; 141(6): 588-593, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33823755

RESUMO

BACKGROUND: Long-term use of a unilateral cochlear implant (CI) may lead to abnormal development of contralateral auditory pathway. OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem response (eABR) with the electrical stimulation at the round window membrane and the effect of unilateral CI use on the contralateral auditory pathway functions. MATERIALS AND METHODS: According to duration of unilateral CI use, 45 children with severe or profound sensorineural hearing loss were divided into sCI (≤12 months), lCI (≥24 months) and nCI (no CI use) groups. Intra-operative eABRs evoked by electrical stimulation at the round window membrane were recorded. RESULTS: The latencies of eIII and eV were significantly longer in lCI group than in sCI group and in nCI group, respectively, but not significantly different between sCI group and nCI group. The eABR thresholds and eIII-eV latency intervals were not significantly different among three groups. CONCLUSIONS AND SIGNIFICANCE: The eABR evoked by the electrical stimulation at the round window membrane is a reliable and effective way of evaluating functions of the auditory pathway in deaf children. Long-term use of a unilateral CI may promote the degenerative process of the contralateral auditory pathway to the level of the brainstem.


Assuntos
Vias Auditivas/fisiopatologia , Implantes Cocleares , Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva Neurossensorial/fisiopatologia , Janela da Cóclea/fisiopatologia , Adolescente , Limiar Auditivo/fisiologia , Criança , Pré-Escolar , Estimulação Elétrica , Feminino , Humanos , Lactente , Masculino
16.
Neural Regen Res ; 16(6): 1044-1051, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33269749

RESUMO

Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, and it may be neuroprotective against cerebral ischemia injury. However, the precise mechanisms of the effects of apelin-13 remain to be elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury, a rat model was established by middle cerebral artery occlusion. Apelin-13 (50 µg/kg) was injected into the right ventricle as a treatment. In addition, an SH-SY5Y cell model was established by oxygen-glucose deprivation/reperfusion, with cells first cultured in sugar-free medium with 95% N2 and 5% CO2 for 4 hours and then cultured in a normal environment with sugar-containing medium for 5 hours. This SH-SY5Y cell model was treated with 10-7 M apelin-13 for 5 hours. Results showed that apelin-13 protected against cerebral ischemia/reperfusion injury. Apelin-13 treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and significantly decreasing cleaved caspase-3 expression. In addition, apelin-13 significantly inhibited excessive autophagy by regulating the expression of LC3B, p62, and Beclin1. Furthermore, the expression of Bcl-2 and the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was markedly increased. Both LY294002 (20 µM) and rapamycin (500 nM), which are inhibitors of the PI3K/Akt/mTOR pathway, significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13. In conclusion, the findings of the present study suggest that Bcl-2 upregulation and mTOR signaling pathway activation lead to the inhibition of apoptosis and excessive autophagy. These effects are involved in apelin-13-induced neuroprotection against cerebral ischemia/reperfusion injury, both in vivo and in vitro. The study was approved by the Animal Ethical and Welfare Committee of Jining Medical University, China (approval No. 2018-JS-001) in February 2018.

17.
J Neural Eng ; 17(3): 036014, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32380482

RESUMO

OBJECTIVE: Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients who have pharmaco-resistant Dravet syndrome (DS). Plentiful efforts have been made for delivering VNS to DS patients, but its effectiveness still requires further verification. We investigated the effectiveness of the VNS treatment of DS patients using brain connectivity analysis with electroencephalography (EEG). APPROACH: Twenty pharmaco-resistant DS patients were selected to undergo VNS implantation and classified into responder and non-responder groups after 24 months post-VNS. The effect of VNS between 6 months pre- and 6, 12, and 24 months post-VNS in all patients, responders, and non-responders on four different frequency categories of four brain parameters were compared using resting-state EEG. MAIN RESULTS: In alpha and beta bands, all patients showed positive results for characteristic path length (CPL), global efficiency (GE), and transitivity after VNS treatment, and changes in betweenness centrality (BC) were not significant. The difference in transitivity between responders and non-responders is more pronounced than those in CPL and GE are, in both the alpha (p < 0.015) and beta (p < 0.001) bands. There was an obvious change in BC, especially in the alpha band, as the hubs tended to move from frontal lobe to parietal lobe for responders; however, there was no change for the non-responders. SIGNIFICANCE: We investigated the alteration in brain connectivity of DS patients in alpha and beta bands during a long-term follow-up and found the responders have a decreased transitivity after the VNS treatment. Moreover, the hubs with high values in the alpha band tended to move from frontal lobe to parietal lobe for responders after VNS treatment.


Assuntos
Epilepsias Mioclônicas , Estimulação do Nervo Vago , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/terapia , Humanos , Resultado do Tratamento , Nervo Vago
18.
Cancers (Basel) ; 12(4)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32340193

RESUMO

Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including ImlygicTM, an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angiogenesis inhibition on endothelial cell activation has not been previously described. Here, we tested the effects of Rapid Antiangiogenesis Mediated By Oncolytic Virus (RAMBO), an oHSV which expresses a potent anti-angiogenic gene Vasculostatin on endothelial cell activation in heavily vascularized solid tumors. oHSV treatment induces endothelial cell activation, which inhibits virus propagation and oncolysis in adjacent tumor cells in vitro. Consistently, this was also observed in intravital imaging of intracranial tumor-bearing mice in vivo where infected tumor endothelial cells could efficiently clear the virus without cell lysis. Quantitative real-time PCR (Q-PCR), leukocyte adhesion assay, and fluorescent microscopy imaging data, however, revealed that RAMBO virus significantly decreased expression of endothelial cell activation markers and leukocyte adhesion, which in turn increased virus replication and cytotoxicity in endothelial cells. In vivo RAMBO treatment of subcutaneously implanted sarcoma tumors significantly reduced tumor growth in mice bearing sarcoma compared to rHSVQ. In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.

19.
Sci Rep ; 10(1): 1097, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974410

RESUMO

p53 and aldehyde dehydrogenase (ALDH) have been implicated in key tumorigenesis processes including cancer initiating cell (CIC) maintenance; however, the relationship between these two mediators remains poorly defined. In this study, ALDH isoform expression diversity was revealed in CICs with disparate p53 functional states: gain of function, high risk p53 mutation (p53HRmut) and wildtype p53 (p53WT) inactivated by the human papillomavirus 16 (HPV16) E6 oncogene. Interrogation of head and neck squamous cell carcinoma (HNSCC) cell lines and patient tumors showed that HPV16+/p53WT cases have higher ALDH variance score (AVS), a measure of tumor ALDH isoform expression diversity, compared to HPV-/p53HRmut cases (p = 0.03). AVS and several individual ALDH isoforms were associated with prognosis in HPV16+/p53WT HNSCC but not in HPV-/p53HRmut HNSCC. Knockdown of the dominant ALDH isoform in high AVS HNSCC depleted the CIC pool in vitro and in vivo. Our results demonstrate that p53 functional states are associated with distinct ALDH isoform transcriptomic signatures. Moreover, tumor ALDH profiling may provide insight on which ALDH isoform to target in high AVS HNSCC tumors to deplete the CIC population.


Assuntos
Aldeído Desidrogenase/genética , Infecções por Papillomavirus/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiologia , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Células-Tronco Neoplásicas/metabolismo , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/enzimologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transcriptoma , Proteína Supressora de Tumor p53/genética
20.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 311-314, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31544415

RESUMO

OBJECTIVE: To understand the epidemiological features and changing patterns of intestinal parasitic diseases in Jiangxi Province from 1989 to 2014, so as to provide scientific evidence for formulating the preventive and control strategy for intestinal parasitic diseases. METHODS: The data regarding the status of intestinal parasitic diseases in Jiangxi Province were captured from the 1989 national survey on the distribution of human parasites in China and the 2014 national survey on major human parasitic diseases in China, and the status of human intestinal parasite infections was compared between the two surveys in Jiangxi Province. RESULTS: The prevalence rate of human intestinal parasite infections was 79.59% and 9.64% in Jiangxi Province in 1989 and 2014, with a decline rate of 87.89% during the 25-year period (χ2 = 30 870.5, P < 0.01). There were 24 and 20 species of human intestinal parasites detected in Jiangxi Province in 1989 and 2014, respectively, with totally 26 species detected during the two surveys. In Jiangxi Province, the 3 most highly prevalent human intestinal parasites included Ascaris lumbricoides (71.06%), hookworm (17.61%) and Enterobius vermicularis (17.59%) in 1989, and E. vermicularis (13.73%), hookworm (4.66%), whipworm (0.95%) in 2014. A higher rate of human intestinal parasite infections was found in females than in males in both surveys in Jiangxi Province (P < 0.01), and the prevalence of human intestinal parasite infections reduced by 82.50% to 95.31% in different age groups in Jiangsu Province during the 25-year period. CONCLUSIONS: The prevalence of human intestinal parasite infections shows a remarkable decline tendency in Jiangxi Province, and soil-transmitted nematodes remain the main species of human intestinal parasites in Jiangxi Province.


Assuntos
Enteropatias Parasitárias , Ancylostomatoidea , Animais , Ascaris lumbricoides , China/epidemiologia , Enterobius , Feminino , Humanos , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Masculino , Prevalência , Inquéritos e Questionários
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