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Systemic inflammation with alterations in inflammatory markers is involved in aging and Alzheimer's disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during aging and Alzheimer's disease, and specific markers contributing to Alzheimer's disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical Alzheimer's disease, 154) and a cross-sectional cohort (cohort 2: n = 351; controls, 62; Alzheimer's disease, 63; vascular dementia, 58; Parkinson's disease dementia, 56; behavioural variant frontotemporal dementia, 57; dementia with Lewy bodies, 55) were included. Plasma levels of inflammatory markers were measured every 2 years during a 10-year follow-up in the longitudinal cohort and once in the cross-sectional cohort. The study demonstrated that the inflammatory markers significantly altered during both aging and the development of Alzheimer's disease. However, only complement C3, interleukin-1ß, and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their longitudinal changes were significantly associated with the development of Alzheimer's disease compared to controls over the 10-year follow-up. In the cross-sectional cohort, complement C3 demonstrates specificity to Alzheimer's disease, while interleukin-1ß and interleukin-6 were also altered in other dementias. The study provides a new perspective on the involvement of inflammatory markers in the aging process and the development of Alzheimer's disease, implying that regulating inflammation may have a pivotal role in promoting successful aging and in the prevention and treatment of Alzheimer's disease.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss. The main pathological features are neuronal fibrillary tangles caused by amyloid beta deposition and hyperphosphorylation of tau protein, accompanied by neuronal death and loss of synaptic structure. Early diagnosis is the key to the treatment of AD. It is known that some small molecular components are related to the pathogenesis of AD. This article will summarize the common AD biomarkers in cerebrospinal fluid and blood and analyze the current status of AD biomarkers and future research directions. This review summarizes the promising biomarkers for the diagnosis of AD in the last decade and describes their changes in AD body fluids. The diagnostic biomarkers related to AD were mainly distributed in cerebrospinal fluid and blood. Significant changes in these molecules can be detected in cerebrospinal fluid and blood, and they are correlated with AD severity. These humoral molecules have necessary relationship with AD and can be used as AD biomarkers to assist early diagnosis of AD.
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Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Humanos , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Precoce , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/sangue , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidianoRESUMO
Gastric-type endocervical adenocarcinoma (GEA) is an uncommon and highly aggressive malignancy, characterized by non-specific clinical manifestations. The limited number of documented cases poses significant challenges in achieving an early preoperative diagnosis. In the present study, two cases of GEA in female patients, aged 46 and 39 years, who presented with the chief complaint of profuse vaginal discharge are described. Both patients underwent a total hysterectomy and bilateral adnexectomy, leading to the definitive diagnosis of GEA through routine pathological and immunohistochemical examination. Following surgery, case one received conventional chemotherapy with paclitaxel and carboplatin, demonstrating no evidence of recurrence during a follow-up period of >2 years. At present, patient B has been followed up for >1 year without any signs of disease recurrence. Given the rarity and diagnostic challenges associated with GEA, further investigations into its pathogenesis and diagnostic modalities are warranted. Additionally, due to its poor prognosis, close surveillance is essential for monitoring potential recurrences. Reporting such cases is crucial in aiding clinicians to make accurate diagnoses and treatment decisions.
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OBJECTIVES: The purpose of our study is to further understanding of the depression symptoms of HIV/AIDS patients in Guilin, Guangxi via exploring whether there is a mediating effect of sleep quality on medical-social support and depression symptoms and therefore provide a theoretical basis for application of medical-social support to alleviate depression symptoms of HIV/AIDS patients. METHODS: A convenience sampling method was used to select 200 HIV/AIDS patients for the study. Depression symptoms, sleep quality, and medical-social support of the study participants were investigated using The Center for Epidemiological Studies Depression Scale (CES-D), The Pittsburg Sleep Quality Index (PSQI), and The Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Predictors of depression symptoms were explored by multiple linear regression, and Pearson correlation was used to analyze the relationship between sleep quality, medical-social support, and depression symptoms. Mediating effect analysis was performed by nonparametric Bootstrap test. RESULTS: In this study, the incidence of depression symptoms was 54.4%. Multiple linear regression analysis showed that leanness (ß = 0.161, P = 0.008), obesity (ß = 0.186, P = 0.002), sleep quality score > 7 (ß = 0.331, P < 0.001), and medical-social support score > 56 (ß = -0.247, P < 0.001) could influence depression symptoms of HIV and Pearson's correlation analysis demonstrated that there was a two-way correlation between sleep quality, medical social support and depression symptoms (P < 0.05). In addition, Bootstrap tests showed that medical-social support might affect depression symptoms not only directly but also indirectly through the mediating effect of sleep quality with the direct and mediating effects accounting for 77.25% and 22.75% of the total effect, respectively. CONCLUSION: The prevalence of depression symptoms is high among HIV/AIDS patients in Guilin City. The depressive symptoms of PLWHs(people living with HIV) are related to their sleep quality and medical-social support, and sleep quality partially mediates the relationship between medical-social support and depression symptoms. Therefore, interventions to improve sleep quality and medical-social support have the potential to allay the depression symptoms of HIV/AIDS patients.
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Depressão , Infecções por HIV , Qualidade do Sono , Apoio Social , Humanos , Masculino , Feminino , Depressão/epidemiologia , Adulto , Infecções por HIV/psicologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Síndrome da Imunodeficiência Adquirida/psicologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Estudos Transversais , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Synaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer's disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD. METHODS: In this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated. RESULTS: The results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects. CONCLUSIONS: Synaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.
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Doença de Alzheimer , Disfunção Cognitiva , Vesículas Extracelulares , Humanos , Camundongos , Animais , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Sinaptotagmina I , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Neurogranina/líquido cefalorraquidiano , Disfunção Cognitiva/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Atrofia/complicações , Atrofia/patologia , BiomarcadoresRESUMO
This study aimed to assess the utility of serum YKL-40 and serum dipeptidyl peptidase IV (DPP4) as biomarkers for distinguishing between type 2 (T2)-high and T2-low asthma in the Chinese population. Additionally, we sought to explore the associations of serum YKL-40 and DPP4 levels with asthma characteristics and conventional markers. A real-world observational cross-sectional study was conducted, involving a total of 75 adult asthma patients. We collected general information, including demographics and medical history. Measurements included complete blood count, fractional exhaled nitric oxide (FeNO), post-bronchodilator spirometry, serum YKL-40 and serum DPP4 levels. Asthma endotypes, T2-high and T2-low, were defined through a comprehensive review of existing literature and expert group discussions. Logistic and linear regression models were employed. Our findings indicated no significant association between serum YKL-40 or serum DPP4 levels and T2-high asthma across all models. In the fully adjusted model, their odds ratios (OR) were 0.967 (95% CI: 0.920-1.017) and 0.997 (95% CI: 0.993-1.001), respectively. Notably, serum YKL-40 exhibited a positive correlation with FeNO (ßâ =â 0.382, 95% CI: 0.230-0.533) after adjusting for confounding factors. This association, however, diminished in patients under 40 years old (Pâ =â .24), males (Pâ =â .25), and those with FEV1%pred of 80% or higher (Pâ =â .25). Serum DPP4 demonstrated a negative correlation with FEV1/FVC in the fully adjusted model (ß: -0.005, 95% CI: -0.009, -0.000). Among Chinese adult asthma patients, a positive correlation was observed between serum YKL-40 levels and FeNO in females aged over 40 with FEV1%pred less than 80%. Additionally, a weak negative correlation was found between serum DPP4 levels and FEV1/FVC. However, neither serum YKL-40 nor serum DPP4 levels exhibited the capability to differentiate between T2-high and T2-low asthma.
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Asma , Dipeptidil Peptidase 4 , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Proteína 1 Semelhante à Quitinase-3 , Estudos Transversais , Óxido Nítrico/análise , Biomarcadores , China/epidemiologiaRESUMO
Plasma amyloid-ß (Aß)42, phosphorylated tau (p-tau)181, and neurofilament light chain (NfL) are promising biomarkers of Alzheimer's disease (AD). However, whether these biomarkers can predict AD in Chinese populations is yet to be fully explored. We therefore tested the performance of these plasma biomarkers in 126 participants with preclinical AD and 123 controls with 8-10 years of follow-up from the China Cognition and Aging Study. Plasma Aß42, p-tau181, and NfL were significantly correlated with cerebrospinal fluid counterparts and significantly altered in participants with preclinical AD. Combining plasma Aß42, p-tau181, and NfL successfully discriminated preclinical AD from controls. These findings were validated in a replication cohort including 51 familial AD mutation carriers and 52 non-carriers from the Chinese Familial Alzheimer's Disease Network. Here we show that plasma Aß42, p-tau181, and NfL may be useful for predicting AD 8 years before clinical onset in Chinese populations.
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Doença de Alzheimer , Biomarcadores , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Peptídeos beta-Amiloides , Biomarcadores/sangue , População do Leste Asiático , Proteínas tauRESUMO
Bocaparvovirus is an expansive genus of the Parvovirinae, with a wide range of vertebrate hosts. This study investigates Canine minute virus (CnMV), Rat bocavirus (RBoV), and Porcine bocavirus 1 (PBoV1). Both CnMV and PBoV1 have been found in gastrointestinal infections in their respective hosts, with CnMV responsible for spontaneous abortions in dogs, while PBoV has been associated with encephalomyelitis in piglets. The pathogenicity of the recently identified RBoV is currently unknown. To initiate the characterization of these viruses, their capsids structures were determined by cryo-electron microscopy at resolutions ranging from 2.3 to 2.7 Å. Compared to other parvoviruses, the CnMV, PBoV1, and RBoV capsids showed conserved features, such as the channel at the fivefold symmetry axis. However, major differences were observed at the two- and threefold axes. While CnMV displays prominent threefold protrusions, the same region is more recessed in PBoV1 and RBoV. Furthermore, the typical twofold axis depression of parvoviral capsids is absent in CnMV or very small in PBoV and RBoV. These capsid structures extend the structural portfolio for the Bocaparvovirus genus and will allow future characterization of these pathogens on a molecular level. This is important, as no antivirals or vaccines exist for these viruses.
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Bocavirus , Infecções por Parvoviridae , Animais , Ratos , Suínos , Cães , Microscopia Crioeletrônica , Proteínas do Capsídeo/análise , Capsídeo/química , Infecções por Parvoviridae/veterináriaRESUMO
HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site mutations R132T and T216I rescue infectivity. Capsid lattice stability was studied by solving seven crystal structures (in native background), including P38A, P38A/T216I, E45A, E45A/R132T CA, using molecular dynamics simulations of lattices, cryo-electron microscopy of assemblies, time-resolved imaging of uncoating, biophysical and biochemical characterization of assembly and stability. We report pronounced and subtle, short- and long-range rearrangements: (1) A38 destabilized hexamers by loosening interactions between flanking CA protomers in P38A but not P38A/T216I structures. (2) Two E45A structures showed unexpected stabilizing CANTD-CANTD inter-hexamer interactions, variable R18-ring pore sizes, and flipped N-terminal ß-hairpin. (3) Altered conformations of E45Aa α9-helices compared to WT, E45A/R132T, WTPF74, WTNup153, and WTCPSF6 decreased PF74, CPSF6, and Nup153 binding, and was reversed in E45A/R132T. (4) An environmentally sensitive electrostatic repulsion between E45 and D51 affected lattice stability, flexibility, ion and water permeabilities, electrostatics, and recognition of host factors.
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Proteínas do Capsídeo , HIV-1 , Proteínas do Capsídeo/genética , HIV-1/genética , Microscopia Crioeletrônica , Capsídeo , BiofísicaRESUMO
In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
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Adeno-associated viruses (AAVs) are non-enveloped ssDNA icosahedral T = 1 viruses used as vectors for clinical gene delivery. Currently, there are over 200 AAV-related clinical trials and six approved biologics on the market. As such new analytical methods are continually being developed to characterize and monitor the quality and purity of manufactured AAV vectors, these include ion-exchange chromatography and Direct Mass Technology. However, these methods require homogeneous analytical standards with a high molecular weight standard comparable to the mass of an AAV capsid. Described here is the design, production, purification, characterization, and the cryo-electron microscopy structure of an AAV1-VP3-only capsid that fulfills this need as a calibrant to determine capsid mass, charge, homogeneity, and transgene packaging characteristics.
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Purpose: The purpose of our study is to understand the current status of depression and medical social support in elderly HIV/AIDS, as well as the role of social support on depression, so as to provide a certain reference for reducing the occurrence of depression in the population. Methods: A total of 115 participants with PLWHA (people living with HIV/AIDS) aged 50 years or older were collected in Guilin from December 2021 to July 2022. Depression and medical social support were assessed using the Center for Streaming Depression Scale (CES-D) and the Medical Social Support Scale (MOS-SSS). The structural equation model was used to examine the relationship between medical social support and depression. Results: Sixty-one of 115 participants developed depressive symptoms with a prevalence of 53.0%. The results of univariate analysis showed that ethnicity, health status, mean monthly income, antiviral treatment status, and medical social support influenced PLWHA depression (P<0.05). Simple linear regression showed that health status (95% CI: -9.901~-2.635), and antiviral treatment status (95% CI: -12.969~-3.394) influent depression (P<0.05). There were associations between total medical social support, practical support dimension, message and emotional support dimension, social interactive cooperation dimension, emotional support dimension and depression (unadjusted and adjusted for contextual factors) (P < 0.05). Using multiple linear regression analyses, we found that medical-social support was negatively associated with depression with a standardized effect value of -0.223. PLWHA with higher medical social support had lower prevalence of depression. Conclusion: The results indicate that the prevalence of depression among HIV/AIDS patients in Guilin is high. So the joint efforts of individuals, families, and society are needed to improve the physical and mental health of the PLWHA.
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BACKGROUND: Messenger RNAs (mRNAs) have been reported to be associated with Alzheimer's disease (AD). In this study, we investigated whether plasma-based mRNAs could distinguish AD from cognitively normal controls and other types of dementia, including vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Plasma mRNA expression was measured in three independent datasets. Dataset 1 (n = 40; controls, 20; AD, 20) was used to identify the differentially expressed mRNAs. Dataset 2 (n = 122; controls: 60; AD: 62) was used to develop a diagnostic AD model using an mRNA panel. Furthermore, we applied the model to Dataset 3 (n = 334; control, 57; AD, 58; VaD, 55; PDD, 54; bvFTD, 55; DLB, 55) to verify its ability to identify AD and other types of dementia. RESULTS: Dataset 1 showed 22 upregulated and 21 downregulated mRNAs. A panel of six mRNAs distinguished AD from the control group in Dataset 2. The panel was used to successfully differentiate AD from other types of dementia in Dataset 3. CONCLUSIONS: An AD-specific panel of six mRNAs was created that can be used for AD diagnosis.
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Doença de Alzheimer , Demência Vascular , Demência Frontotemporal , Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/genética , Doença de Parkinson/diagnóstico , Demência Vascular/diagnóstico , Demência Vascular/genética , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/genéticaRESUMO
The prediction of cyber security situation plays an important role in early warning against cyber security attacks. The first-order accumulative grey model has achieved remarkable results in many prediction scenarios. Since recent events have a greater impact on future decisions, new information should be given more weight. The disadvantage of first-order accumulative grey models is that with the first-order accumulative method, equal weight is given to the original data. In this paper, a fractional-order cumulative grey model (FAGM) is used to establish the prediction model, and an intelligent optimization algorithm known as particle swarm optimization (PSO) combined with a genetic algorithm (GA) is used to determine the optimal order. The model discussed in this paper is used for the prediction of Internet cyber security situations. The results of a comparison with the traditional grey model GM(1,1), the grey model GM(1,n), and the fractional discrete grey seasonal model FDGSM(1,1) show that our model is suitable for cases with insufficient data and irregular sample sizes, and the prediction accuracy and stability of the model are better than those of the other three models.
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Algoritmos , PrevisõesRESUMO
Advances in electron detection have been essential to the success of high-resolution cryo-EM structure determination. A new generation of direct electron detector called the Apollo, has been developed by Direct Electron. The Apollo uses a novel event-based MAPS detector custom designed for ultra-fast electron counting. We have evaluated this new camera, finding that it delivers high detective quantum efficiency (DQE) and low coincidence loss, enabling high-quality electron counting data acquisition at up to nearly 80 input electrons per pixel per second. We further characterized the performance of Apollo for single particle cryo-EM on real biological samples. Using mouse apoferritin, Apollo yielded better than 1.9 Å resolution reconstructions at all three tested dose rates from a half-day data collection session each. With longer collection time and improved specimen preparation, mouse apoferritin was reconstructed to 1.66 Å resolution. Applied to a more challenging small protein aldolase, we obtained a 2.24 Å resolution reconstruction. The high quality of the map indicates that the Apollo has sufficiently high DQE to reconstruct smaller proteins and complexes with high-fidelity. Our results demonstrate that the Apollo camera performs well across a broad range of dose rates and is capable of capturing high quality data that produce high-resolution reconstructions for large and small single particle samples.
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Parvoviruses are small, single-stranded DNA viruses with non-enveloped capsids. Determining the capsid structures provides a framework for annotating regions important to the viral life cycle. Aleutian mink disease virus (AMDV), a pathogen in minks, and human parvovirus 4 (PARV4), infecting humans, are parvoviruses belonging to the genera Amdoparvovirus and Tetraparvovirus, respectively. While Aleutian mink disease caused by AMDV is a major threat to mink farming, no clear clinical manifestations have been established following infection with PARV4 in humans. Here, the capsid structures of AMDV and PARV4 were determined via cryo-electron microscopy at 2.37 and 3.12 Å resolutions, respectively. Despite low amino acid sequence identities (10-30%) both viruses share the icosahedral nature of parvovirus capsids, with 60 viral proteins (VPs) assembling the capsid via two-, three-, and five-fold symmetry VP-related interactions, but display major structural variabilities in the surface loops when the capsid structures are superposed onto other parvoviruses. The capsid structures of AMDV and PARV4 will add to current knowledge of the structural platform for parvoviruses and permit future functional annotation of these viruses, which will help in understanding their infection mechanisms at a molecular level for the development of diagnostics and therapeutics.
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Vírus da Doença Aleutiana do Vison , Infecções por Parvoviridae , Parvovirus , Animais , Humanos , Vírus da Doença Aleutiana do Vison/genética , Capsídeo/química , Microscopia Crioeletrônica , DNA de Cadeia Simples , Proteínas do Capsídeo/genética , Parvovirus/genética , Infecções por Parvoviridae/veterinária , Vison , Proteínas Virais/genéticaRESUMO
Lateral organ boundaries domain (LBD) proteins, a class of plant-specific transcription factors with a special domain of lateral organ boundaries (LOB), play essential roles in plant growth and development. However, there is little known about the functions of these genes in wheat to date. Our previous study demonstrated that TaLBD16-4D is conducive to increasing lateral root number in wheat. In the present work, we further examined important agronomical traits of the aerial part of transgenic wheat overexpressing TaLBD16-4D. Interestingly, it was revealed that overexpressing TaLBD16-4D could lead to early heading and multiple alterations of plant architecture, including decreased plant height, increased flag leaf size and stem diameter, reduced spike length and tillering number, improved spike density and grain width, and decreased grain length. Moreover, auxin-responsive experiments demonstrated that the expression of TaLBD16-4D in wild-type (WT) wheat plants showed a significant upregulation through 2,4-D treatment. TaLBD16-4D-overexpression lines displayed a hyposensitivity to 2,4-D treatment and reduced shoot gravitropic response. The expressions of a set of auxin-responsive genes were markedly different between WT and transgenic plants. In addition, overexpressing TaLBD16-4D affected the transcript levels of flowering-related genes (TaGI, TaCO1, TaHd1, TaVRN1, TaVRN2, and TaFT1). Notably, the expression of TaGI, TaCO1, TaHd1, TaVRN1, and TaFT1 displayed significant upregulation under IAA treatment. Collectively, our observations indicated that overexpressing TaLBD16-4D could affect aerial architecture and heading time possibly though participating in the auxin pathway.
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Large fetal head and neck tumors are being increasingly identified during prenatal examination and tend to have a poor prognosis. Nevertheless, appropriate intrauterine interventions at suitable periods can improve pregnancy outcome. Ultrasound-guided puncture biopsy of the solid fetal head and neck mass and radiofrequency ablation of a portion of the tissue can clarify the tumor pathology and reduce the tumor size, respectively. These treatment methods are reproducible and associated with reduced trauma and complications.
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Alzheimer disease (AD) is a neurodegenerative disorder, which is characterized by progressive impairment of memory and cognition. Early diagnosis and treatment of AD has become a leading topic of research. In this study, we explored the effects of the miR-132-3p/FOXO3a-PPM1F axis on the onset of AD for possible early diagnosis and therapy. We found that miR-132-3p levels in the hippocampus and blood were drastically decreased in APP/PS1 mice from 9 months of age, and bi-directional manipulation of miR-132-3p levels induced magnified effects on learning memory behaviors, and manifestation of AD-related pathological characteristics and inflammatory cytokines in APP/PS1 mice of relevant ages. The hippocampal PPM1F expression levels were significantly elevated in APP/PS1 mice from 3 months of age, which was correlated with miR-132-3p levels at different ages. Overexpression of PPM1F remarkably accelerated the progression of learning memory deficits and associated pathological factors in APP/PS1 mice. Further, we showed that miR-132-3p modulated the expression of PPM1F via FOXO3a in HT22 cells. Finally, using peripheral blood samples of human study participants, we found that the miR-132-3p and PPM1F expression levels in patients with AD were also altered with prominent correlations. In conclusion, miR-132-3p indirectly regulates PPM1F expression by targeting FOXO3a, which could play an extensive role in contributing to the establishment of early diagnosis, treatment, and pathogenesis of AD.
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Doença de Alzheimer , MicroRNAs , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Humanos , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , MicroRNAs/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/farmacologia , Fosfoproteínas Fosfatases/uso terapêutico , Presenilina-1/genética , Presenilina-1/metabolismoRESUMO
Ultrasound targeted microbubble destruction (UTMD) was introduced as a promising method to improve anti-tumor therapeutic efficacy, while minimizing side effects to healthy tissues. Nevertheless, the acoustical phenomenon behind the UTMD as well as the exact mechanisms of autophagy action involved in the increased anti-cancer response are still not fully understood. Therefore, we examined the drug resistance-reversing effects of low-intensity focused ultrasound with microbubble (LIFU+MB) in paclitaxel (PTX)-resistant ovarian cancer cells. Cell viability was evaluated using CCK8 (Cell Counting Kit-8), apoptosis was detected by flow cytometry, quantitative real-time PCR and Western blot were used to detect the expressions of mRNA and protein, and autophagy was observed by transmission electron microscopy (TEM). We revealed that the level of autophagy was increased (p < 0.05) in PTX-resistant ovarian cancer cells. Treatment of LIFU+MB combined with PTX can notably inhibit proliferation as well as increase apoptosis (p < 0.01) in drug-resistant cells. We proposed that LIFU+MB might affect the sensitivity of ovarian cancer cells to PTX by modulating autophagy. To verify the hypothesis, we analyzed the autophagy level of drug-resistant cells after the treatment of LIFU+MB and found that autophagy was significantly inhibited. Altogether, our findings demonstrated that LIFU+MB could reverse PTX resistance in ovarian cancer via inhibiting autophagy, which provides a novel strategy to improve chemosensitivity in ovarian cancer.