Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 147
Filtrar
1.
PLoS Pathog ; 20(4): e1012116, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38557908

RESUMO

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.


Assuntos
COVID-19 , Vacinas de mRNA , Animais , Humanos , Camundongos , Vacinas contra COVID-19 , Macaca mulatta , COVID-19/prevenção & controle , Imunização Secundária , Camundongos Transgênicos , RNA Mensageiro/genética , SARS-CoV-2/genética , Anticorpos Neutralizantes , Anticorpos Antivirais
2.
J Food Prot ; 87(6): 100276, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615993

RESUMO

Governments use policy interventions to mitigate food safety risks. Despite its crucial role, empirical studies evaluating the effectiveness of China's food safety policy tools are scarce. Drawing on a dataset encompassing 11,236 food safety policy texts from 2005 to 2021 and the incidence of problematic food products in the Eastern, Central, and Western regions of China, this study employs Latent Dirichlet Allocation (LDA) and eXtreme Gradient Boosting (XGBoost) models to facilitate the classification of policy tools and forecast the effectiveness of policy combinations. The study reveals that (1) local governments have gradually become an important supplementary maker of food safety policies, and have issued an increasing number of policy tools year by year. (2) Mandatory policy tools are predominant in number and have the highest legal hierarchy and authority levels, followed successively by guiding policy and voluntary policy tools. (3) Mandatory policy tools demonstrated the most effective intervention results, followed successively by guiding policy and voluntary policy tools. (4) The forecast analysis reveals that combinations of policies within high-growth frameworks and those driven by mandatory regulations emerge as the most effective. Therefore, the balance of policy tools in terms of type, effectiveness, and quantity, as well as their applicability in different situations, should all be taken into account.

3.
Sci Rep ; 14(1): 7277, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538669

RESUMO

MicroRNAs (miRNAs) are vital regulators of tumor pathogenesis, including that of retinoblastoma (Rb). This study investigated the functions and mechanisms of action of miR-889-3p in Rb. BMPR2 and miR-889-3p levels were assessed by quantitative reverse transcription PCR (qRT-PCR) or western blotting. Through several cell function tests, the effects of miR-889-3p and BMPR2 on cell proliferation, migration, and JNK/MAPK/ERK signaling were evaluated. The interaction between miR-889-3p and BMPR2 was investigated using a luciferase reporter assay. In vivo tumor development was investigated using a xenograft test. The association between miR-889-3p and BMPR2 expression was identified using Pearson's correlation analysis. miR-889-3p was increased in Rb cells, and miR-889-3p knockdown inhibited Rb cell proliferation, migration, and phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and ERK1/2 in vitro, as well as tumor growth in vivo. Further, they were inversely associated in Rb tissues and miR-889-3p may directly attached to the 3'-UTR of BMPR2 mRNA. Finally, the inhibition of BMPR2 inverted the negative effects of the miR-889-3p inhibitor on migration, proliferation, and activation of JNK, p38 MAPK, and ERK1/2 in Rb cells. Our results indicate that miR-889-3p, which targets BMPR2 and promotes Rb growth by controlling the JNK/MAPK/ERK pathway, is an oncogene in Rb. These results suggested that the miR-889-3p/BMPR2 axis may be a new therapeutic target for Rb.


Assuntos
MicroRNAs , Neoplasias da Retina , Retinoblastoma , Humanos , Retinoblastoma/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Proliferação de Células/genética , Neoplasias da Retina/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Apoptose/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo
4.
Genes (Basel) ; 15(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38540324

RESUMO

Phenylalanine ammonia-lyase (PAL) is an essential enzyme in the phenylpropanoid pathway, in which numerous aromatic intermediate metabolites play significant roles in plant growth, adaptation, and disease resistance. Cultivated peanuts are highly susceptible to Aspergillus flavus L. infection. Although PAL genes have been characterized in various major crops, no systematic studies have been conducted in cultivated peanuts, especially in response to A. flavus infection. In the present study, a systematic genome-wide analysis was conducted to identify PAL genes in the Arachis hypogaea L. genome. Ten AhPAL genes were distributed unevenly on nine A. hypogaea chromosomes. Based on phylogenetic analysis, the AhPAL proteins were classified into three groups. Structural and conserved motif analysis of PAL genes in A. hypogaea revealed that all peanut PAL genes contained one intron and ten motifs in the conserved domains. Furthermore, synteny analysis indicated that the ten AhPAL genes could be categorized into five pairs and that each AhPAL gene had a homologous gene in the wild-type peanut. Cis-element analysis revealed that the promoter region of the AhPAL gene family was rich in stress- and hormone-related elements. Expression analysis indicated that genes from Group I (AhPAL1 and AhPAL2), which had large number of ABRE, WUN, and ARE elements in the promoter, played a strong role in response to A. flavus stress.


Assuntos
Arachis , Aspergillus flavus , Aspergillus flavus/genética , Arachis/genética , Arachis/metabolismo , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Filogenia , Regiões Promotoras Genéticas
5.
Genome ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394647

RESUMO

For peanut, the lack of stable cytological markers is a barrier to tracking specific chromosomes, elucidating the genetic relationships between genomes and identifying chromosomal variations. Chromosome mapping using single-copy oligonucleotide (oligo) probe libraries has unique advantages for identifying homologous chromosomes and chromosomal rearrangements. In this study, we developed two whole-chromosome single-copy oligo probe libraries, LS-7A and LS-8A, based on the reference genome sequences of chromosomes 7A and 8A of Arachis duranensis. Fluorescence in situ hybridization (FISH) analysis confirmed that the libraries could specifically paint chromosomes 7 and 8. In addition, sequential FISH and electronic localization of LS-7A and LS-8A in A. duranensis (AA) and A. ipaensis (BB) showed that chromosomes 7A and 8A contained translocations and inversions relative to chromosomes 7B and 8B. Analysis of the chromosomes of wild Arachis species using LS-8A confirmed that this library could accurately and effectively identify A genome species. Finally, LS-7A and LS-8A were used to paint the chromosomes of interspecific hybrids and their progenies, which verified the authenticity of the interspecific hybrids and identified a disomic addition line. This study provides a model for developing specific oligo probes to identify the structural variations of other chromosomes in Arachis and demonstrates the practical utility of LS-7A and LS-8A.

6.
Environ Sci Pollut Res Int ; 31(14): 21986-22011, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38400970

RESUMO

Accurate small-sample prediction is an urgent, very difficult, and challenging task due to the quality of data storage restricted in most realistic situations, especially in developing countries. The grey model performs well in small-sample prediction. Therefore, a novel multivariate grey model is proposed in this study, called FBNGM (1, N, r), with a fractional order operator, which can increase the impact of new information and background value coefficient to achieve high prediction accuracy. The utilization of an intelligence optimization algorithm to tune the parameters of the multivariate grey model is an improvement over the conventional method, as it leads to superior accuracy. This study conducts two sets of numerical experiments on CO2 emissions to evaluate the effectiveness of the proposed FBNGM (1, N, r) model. The FBNGM (1, N, r) model has been shown through experiments to effectively leverage all available data and avoid the problem of overfitting. Moreover, it can not only obtain higher prediction accuracy than comparison models but also further confirm the indispensable importance of various influencing factors in CO2 emissions prediction. Additionally, the proposed FBNGM (1, N, r) model is employed to forecast CO2 emissions in the future, which can be taken as a reference for relevant departments to formulate policies.


Assuntos
Algoritmos , Dióxido de Carbono , Dióxido de Carbono/análise , Previsões , China
8.
Asian J Surg ; 47(4): 1734-1739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185563

RESUMO

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Deglutição , Músculos do Pescoço/patologia , Endoscopia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia
9.
Mol Biotechnol ; 66(1): 102-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37041423

RESUMO

Retinoblastoma (RB) is a malignant ocular cancer that affects children. Several microRNAs (miRNAs) have been implicated in RB regulation. The present study aimed to investigate the role of miR-4529-3p in RB pathogenesis. Scratch, Transwell, and Cell Counting Kit (CCK)-8 assays were conducted to assess the migratory, invasive, and proliferative abilities of RB cells. The expression levels of miR-4529-3p, RB1, and ERK pathway-related proteins were analyzed using western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Target relationships were verified using dual-luciferase reporter experiments. A murine RB model was developed to analyze the effects of miR-4529-3p on RB tumor growth in vivo. Our experiments revealed high levels of miR-4529-3p and low levels of RB1 in RB tissues. Functional analyses revealed that the migratory, invasive, and proliferative abilities of RB cells were repressed by miR-4529-3p inhibition. Similarly, p-ERK 1/2 protein levels were suppressed by miR-4529-3p inhibition. Furthermore, downregulation of miR-4529-3p limited tumor growth in vivo. Mechanistically, miR-4259-3p targets RB1. Interestingly, RB1 silencing abrogated the alleviative effects of miR-4529-3p downregulation in RB cells. MiR-4529-3p promotes RB progression by inhibiting RB1 and activating the ERK pathway. This evidence suggests that the miR-4529-3p/RB1 regulatory axis may be a prospective target for RB treatment in clinical settings.


Assuntos
MicroRNAs , Neoplasias da Retina , Retinoblastoma , Criança , Humanos , Animais , Camundongos , Retinoblastoma/genética , Retinoblastoma/metabolismo , Retinoblastoma/patologia , Sistema de Sinalização das MAP Quinases/genética , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais , Neoplasias da Retina/genética , Neoplasias da Retina/metabolismo , Neoplasias da Retina/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Ligação a Retinoblastoma/genética , Proteínas de Ligação a Retinoblastoma/metabolismo
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(11): 1113-1117, 2023 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-37990454

RESUMO

OBJECTIVES: To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups. METHODS: A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions. RESULTS: There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05). CONCLUSIONS: The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.


Assuntos
Vasculite por IgA , Nefrite , Vasculite , Criança , Humanos , Ácido Micofenólico/efeitos adversos , Vasculite por IgA/tratamento farmacológico , Estudos Retrospectivos , Ciclofosfamida/efeitos adversos , Imunossupressores/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/complicações , Vasculite/tratamento farmacológico , Nefrite/etiologia , Nefrite/complicações
12.
Sci Bull (Beijing) ; 68(23): 3003-3012, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37919162

RESUMO

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a significant number of variants, particularly with the emergence of Omicron with many sub-variants. These variants have exhibited increased immune escape, leading to reduced efficacy of existing vaccines and therapeutic antibodies. Given the diminished cross-neutralization observed among these variants, it is plausible that SARS-CoV-2 has developed multiple serotypes. As the major antigenic site, the receptor-binding domain (RBD) of viral spike (S) protein was chosen for serotyping. We selected 23 representative variants, including pre-Omicron variants and Omicron sub-variants, and classified them into five serotypes based on systematic evaluation of the antigenicities of their RBDs. Each serotype includes several genetically distinct variants. Serotype-I encompasses all pre-Omicron variants (with two subtypes), while the remaining four serotypes are all comprised of Omicron sub-variants at different stages of evolution. We propose that these serotypes can serve as a foundation for rapid classification of newly emerging SARS-CoV-2 variants, and guide the development of future broad-spectrum vaccines and neutralizing antibodies against the coronavirus disease 2019 (COVID-19).


Assuntos
COVID-19 , Vacinas , Humanos , SARS-CoV-2/genética , Sorogrupo
13.
Med Sci Monit ; 29: e941937, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37864329

RESUMO

BACKGROUND Lumbar disc herniation (LDH) at L4-L5 impacts paravertebral muscle morphology. Intervertebral disc degeneration is linked to paravertebral muscle changes, affecting LDH treatment outcomes. This study explored L4-L5 LDH paravertebral muscle alterations, specifically in the erector spinae, multifidus, and psoas major, using Michigan State University's classification to guide LDH treatment. MATERIAL AND METHODS The study enrolled 160 patients, including 39 normal patients and 121 L4-L5 LDH patients. Patients with LDH were grouped according to MSU classification and compared to the normal group according to demographics and imaging changes. RESULTS In patients with L4-L5 herniation in Zone B, the FI of the ES muscle at L3-L4 level, L4-L5 level, and L5-S1 level was higher than that of normal people (P=0.018, P=0.043, P=0.010, respectively), and there was no difference between FI of MF and normal people. The Zone B patients also had a smaller CSA of the ES muscle at L4-L5 level than that in the normal group (P=0.049). Patients in the Zone C group were older than those in the normal group (P=0.014). The CSA of the PM of patients with Grade 3 herniation differed from that of the normal group at the L4-L5 and L5-S1 level. They were higher than in normal people at L4-L5 level (P=0.011) and lower at L5-S1 level (P=0.028). CONCLUSIONS In patients with L4-L5 herniation in Zone B, the FI of ES at L3-S1 level was higher than in normal people, and the CSA at L4-L5 level was smaller than in normal people. In patients with Grade3 herniation, PM CSA was larger at L4-L5 level and smaller at L5-S1 level than in normal people.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Humanos , Michigan , Universidades , Vértebras Lombares , Imageamento por Ressonância Magnética/métodos , Músculos Psoas
14.
Front Oncol ; 13: 1274340, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901319

RESUMO

Introduction: Breast cancer is the most common malignancy among women. Previous studies had shown that hepatitis C virus (HCV) infection might serve as a risk factor for breast cancer, while some studies failed to find such an association. Methods: In this study, we presented a first attempt to capture and clarify this clinical debate via a cumulative analysis (registration ID: CRD42023445888). Results: After systematically searching and excluding the irrelevant publications, five case-control or cohort studies were finally included. The synthetic effect from the eligible studies showed that patients with HCV infection had a significantly higher prevalence of breast cancer than non-HCV infected general population (combined HR= 1.382, 95%CI: 1.129 to 1.692, P=0.002). There was no evidence of statistical heterogeneity during this pooled analysis (I2 = 13.2%, P=0.33). The sensitivity analyses confirmed the above findings. No significant publication bias was observed among the included studies. The underlying pathophysiological mechanisms for this relationship might be associated with persistent infection/inflammation, host immune response, and the modulation of HCV-associated gene expression. Discussion: Though the causal association between HCV infection and breast cancer did not seem quite as strong, screening for HCV might enable the early detection of breast cancer and help to prevent the progression of the disease. Since the topic of this study remains a matter of clinical debate, further studies are still warranted to validate this potential association. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023445888.

15.
JCI Insight ; 8(20)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37733446

RESUMO

Abnormal macrophage polarization is generally present in autoimmune diseases. Overwhelming M1 macrophage activation promotes the continuous progression of inflammation, which is one of the reasons for the development of autoimmune diseases. However, the underlying mechanism is still unclear. Here we explore the function of Regulatory factor X1 (RFX1) in macrophage polarization by constructing colitis and lupus-like mouse models. Both in vivo and in vitro experiments confirmed that RFX1 can promote M1 and inhibit M2 macrophage polarization. Furthermore, we found that RFX1 promoted DNA demethylation of macrophage polarization-related genes by increasing APOBEC3A/Apobec3 expression. We identified a potential RFX1 inhibitor, adenosine diphosphate (ADP), providing a potential strategy for treating autoimmune diseases.


Assuntos
Doenças Autoimunes , Ativação de Macrófagos , Animais , Camundongos , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Desmetilação do DNA , Inflamação/metabolismo , Macrófagos/metabolismo , Fator Regulador X1/metabolismo
16.
Mater Horiz ; 10(12): 5656-5665, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37766462

RESUMO

Thermally conductive materials (TCMs) are highly desirable for thermal management applications to tackle the "overheating" concerns in the electronics industry. Despite recent progress, the development of high performance TCMs integrated with an in-plane thermal conductivity (TC) higher than 50.0 W (m K)-1 and a through-plane TC greater than 10.0 W (m K)-1 is still challenging. Herein, self-standing liquid metal@boron nitride (LM@BN) bulks with ultrahigh in-plane TC and through-plane TC were reported for the first time. In the LM@BN bulks, LM could serve as a bonding and thermal linker among the oriented BN platelets, thus remarkably accelerating heat transfer across the whole system. Benefiting from the formation of a unique structure, the LM@BN bulk achieved an ultrahigh in-plane TC of 82.2 W (m K)-1 and a through-plane TC of 20.6 W (m K)-1, which were among the highest values ever reported for TCMs. Furthermore, the LM@BN bulks exhibited superior compressive and leakage-free performances, with a high compressive strength (5.2 MPa) and without any LM leakage even after being crushed. It was also demonstrated that the excellent TCs of the LM@BN bulks made them effectively cool high-power light emitting diode modules. This work opens up one promising pathway for the development of high-performance TCMs for thermal management in the electronics industry.

17.
Biochem Biophys Res Commun ; 678: 186-192, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37643536

RESUMO

BACKGROUND: Chemoresistance, i.e., resistance to cisplatin (DDP), has been a major obstacle to ovarian cancer treatment. It has been found that circular RNAs (circRNAs) play vital roles in the tumorigenesis various cancers by regulating autophagy, while few studies focusing on cisplatin-resistance ovarian cancer (CROC). METHODS: The expressions of the circRNAs were detected by qRT-PCR. Short hairpin RNA targeting circRNA was used to explore the biological functions of the circRNA. Cell viability, autophagic flux, immunofluorescence, and xenograft tumors experiments were performed to further illustrate the underlying mechanisms. RESULTS: Hsa_circ_0000585 was increased in cisplatin-resistant SKOV3/DDP cells. Stably knocking down hsa_circRNA_0000585 expression in SKOV3/DDP cells was established by RNA interference. We found that downregulation of hsa_circ_0000585 significantly enhanced the sensitivity of DDP/SkOV3 cells to DDP. In vivo study, hsa_circRNA_0000585 knockdown significantly decreased tumor volume in nude mice. Under the measurements of western blot and cellular immunofluorescence, hsa_circ_0000585 knockdown significantly inhibited the expression of Beclin1 and P62, indicating the autophagic flux was inhibited. Administrations with autophagic inhibitor "Chloroquine (CQ)" and autophagy activator "QX77" further confirmed that hsa_circ_0000585 knockdown resulted in autophagy inhibition. CONCLUSIONS: Overall, this study provided a new insight into the role of circRNAs in the mechanism of DDP-resistance in ovarian cancer. Hsa_circRNA_0000585 may be promising therapeutic targets for the enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.


Assuntos
Cisplatino , Neoplasias Ovarianas , Humanos , Animais , Camundongos , Feminino , Cisplatino/farmacologia , RNA Circular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Nus , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Células Epiteliais , Autofagia
18.
Sci Rep ; 13(1): 11231, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433857

RESUMO

Occurrence of amyloid-ß (Aß) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep-wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aß levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aß aggregation but without significant differences in cognitive performance had frequent sleep-wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection.


Assuntos
Doença de Alzheimer , Disautonomias Primárias , Camundongos , Animais , Camundongos Transgênicos , Doença de Alzheimer/genética , Sono , Cognição , Peptídeos beta-Amiloides
19.
Abdom Radiol (NY) ; 48(11): 3343-3352, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37495746

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the third leading cause of cancer death worldwide. Studies have shown that increased angiopoietin-2 (Ang-2) expression relative to Ang-1 expression in tumors is associated with a poor prognosis.The purpose of this study was to investigate the efficacy of predicting Ang-2 expression in HCC by preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based radiomics. METHODS: The data of 52 patients with HCC who underwent surgical resection in our hospital were retrospectively analyzed. Ang-2 expression in HCC was analyzed by immunohistochemistry. All patients underwent preoperative upper abdominal DCE-MRI and intravoxel incoherent motion diffusion-weighted imaging scans. Radiomics features were extracted from the early and late arterial and portal phases of axial DCE-MRI. Univariate analysis and least absolute shrinkage and selection operator (LASSO) was performed to select the optimal radiomics features for analysis. A logistic regression analysis was performed to establish a DCE-MRI radiomics model, clinic-radiologic (CR) model and combined model integrating the radiomics score with CR factors. The stability of each model was verified by 10-fold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. RESULTS: Among the 52 HCC patients, high Ang-2 expression was found in 30, and low Ang-2 expression was found in 22. The areas under the ROC curve (AUCs) for the radiomics model, CR model and combined model for predicting Ang-2 expression were 0.800, 0.874, and 0.933, respectively. The DeLong test showed that there was no significant difference in the AUC between the radiomics model and the CR model (p > 0.05) but that the AUC for the combined model was significantly greater than those for the other 2 models (p < 0.05). The DCA results showed that the combined model outperformed the other 2 models and had the highest net benefit. CONCLUSION: The DCE-MRI-based radiomics model has the potential to predict Ang-2 expression in HCC patients; the combined model integrating the radiomics score with CR factors can further improve the prediction performance.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Angiopoietina-2 , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética
20.
Discov Med ; 35(176): 221-232, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37272089

RESUMO

PURPOSE: To develop an ultrasound predictive model to differentiate between benign and malignant complex cystic and solid nodules (C-SNs). METHODS: A total of 211 patients with complex C-SNs rated as American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) category 4 or 5 on the ultrasound reports were included in the study, from June 2018-2021. Multivariate stepwise logistic regression analysis was used to establish a predictive model, based on clinical and ultrasound features. The diagnostic performance of the model was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: A total of 109 breast nodules, including 74 benign nodules (67.89%) and 35 malignant nodules (32.11%), were detected by surgical pathology or puncture biopsy. Multivariate analysis showed that the blood flow (BF) of complex C-SNs (p = 0.03), cystic fluid transmission (p = 0.02), longitudinal diameter (p < 0.001), and age (p = 0.03) were independent risk factors for malignant complex cystic and solid breast nodules. The ultrasound model equation was Z=-12.14+2.24×X12+1.97×X20+0.40×X7+0.11×X0; M=ez1+ez (M is the malignancy score, e = 2.72). The area under the curve (AUC) was 0.89, which indicated good predictive utility for the model. CONCLUSIONS: A prediction model incorporating major risk factors can predict the malignant C-SNs with accuracy.


Assuntos
Mama , Humanos , Estudos Retrospectivos , Ultrassonografia/métodos , Curva ROC , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...