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1.
Sci Rep ; 11(1): 19783, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611209

RESUMO

Deep learning networks have been successfully applied to transfer functions so that the models can be adapted from the source domain to different target domains. This study uses multiple convolutional neural networks to decode the electroencephalogram (EEG) of stroke patients to design effective motor imagery (MI) brain-computer interface (BCI) system. This study has introduced 'fine-tune' to transfer model parameters and reduced training time. The performance of the proposed framework is evaluated by the abilities of the models for two-class MI recognition. The results show that the best framework is the combination of the EEGNet and 'fine-tune' transferred model. The average classification accuracy of the proposed model for 11 subjects is 66.36%, and the algorithm complexity is much lower than other models.These good performance indicate that the EEGNet model has great potential for MI stroke rehabilitation based on BCI system. It also successfully demonstrated the efficiency of transfer learning for improving the performance of EEG-based stroke rehabilitation for the BCI system.

2.
Sci Total Environ ; 806(Pt 2): 150656, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597574

RESUMO

Coral bleaching has become a major threat to coral reefs worldwide, but for most coral species little is known about their resilience to environmental changes. We aimed to understand the gene expressional regulation underlying natural bleaching and recovery in Pavona decussata, a dominant species of scleractinian coral in the northern South China Sea. Analyzing samples collected in 2017 from the field revealed distinct zooxanthellae density, chlorophyll a concentration and transcriptomic signatures corresponding to changes in health conditions of the coral holobiont. In the host, normal-looking tissues of partially bleached colonies were frontloaded with stress responsive genes, as indicated by upregulation of immune defense, response to endoplasmic reticulum, and oxidative stress genes. Bleaching was characterized by upregulation of apoptosis-related genes which could cause a reduction in algal symbionts, and downregulation of genes involved in stress responses and metabolic processes. The transcription factors stat5b and irf1 played key roles in bleaching by regulating immune and apoptosis pathways. Recovery from bleaching was characterized by enrichment of pathways involved in mitosis, DNA replication, and recombination for tissue repairing, as well as restoration of energy and metabolism. In the symbionts, bleaching corresponded to imbalance in photosystems I and II activities which enhanced oxidative stress and limited energy production and nutrient assimilation. Overall, our study revealed distinct gene expressional profiles and regulation in the different phases of the bleaching and recovery process, and provided new insight into the molecular mechanisms underlying the holobiont's resilience that may determine the species' fate in response to global and regional environmental changes.

3.
Placenta ; 115: 97-105, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34598084

RESUMO

INTRODUCTION: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. METHODS: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-κB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. RESULTS: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-κB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. DISCUSSION: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-κB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE.

5.
Biomaterials ; 277: 121115, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34488118

RESUMO

Conductive polymers with high near-infrared absorbance, have attracted considerable attention in the design of intelligent nanomedicines for cancer therapy, especially chemo-photothermal therapy. However, the unknown long-term biosafety of conductive polymers in vivo due to non-degradability hinders their clinic application. Herein, a H2O2-triggered degradable conductive polymer, polyacrylic acid (PAA) stabilized poly(pyrrole-3-COOH) (PAA@PPyCOOH), is fabricated to form nanoparticles with doxorubicin (DOX) for safe and precise chemo-phototherapy. The PAA@PPyCOOH was found to be an ideal photothermal nano-agent with good dispersity, excellent biocompatibility and high photothermal conversion efficiency (56%). After further loading of doxorubicin (DOX), PAA@PPyCOOH@DOX demonstrates outstanding photothermal performance, as well as pH/H2O2 dual-responsive release of DOX in tumors with an acidic and overexpressed H2O2 microenvironment, resulting in superior chemo-photothermal therapeutic effects. The degradation mechanism of PAA@PPyCOOH is proposed to be the ring-opening reaction between the pyrrole-3-COOH unit and H2O2. More importantly, the nanoparticles can be specifically degraded by excess H2O2 in tumor, and the degradation products were confirmed to be excreted via urine and feces. In vivo therapeutic evaluation of chemo-photothermal therapy reveals tumor growth of 4T1 breast cancer model is drastically inhibited and no apparent side-effect is detected, thus indicating substantial potential in clinic application.

6.
Pharm Biol ; 59(1): 1036-1044, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34362284

RESUMO

CONTEXT: Recent studies demonstrated the anti-atherosclerotic efficacy of cyclodextrin. However, it remains unclear whether cyclodextrin exerts the anti-atherosclerotic effect via regulating monocyte-endothelial adhesion. OBJECTIVE: To answer that question by recruiting methyl-ß-cyclodextrin (MßCD) as a cyclodextrin representative. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were not treated, or treated with 1 µg/mL liposaccharide (LPS) or 50 µg/mL oxidized low-density lipoprotein (oxLDL) for 12 h, 5 mM MßCD for 1 h, and LPS/oxLDL (1 and 50 µg/mL, respectively for 12 h) plus MßCD (5 mM for 1 h), respectively. The effects of MßCD on LPS/oxLDL-triggered monocyte-endothelial adhesion and related molecules in signalling pathways were evaluated via confocal microscopy, flow cytometry, RT-PCR, western blotting, and cell adhesion assay. RESULTS: MßCD with an IC50 of 27.66 mM (1 h treatment) exerted no significant cytotoxicity at ≤5 mM for ≤2 h. Compared with the control, both LPS and oxLDL induced an ∼2-3-fold increase in adhesion molecule expression (ICAM-1 and VCAM-1 at protein and mRNA levels) and NF-κB phosphorylation (p-NF-κB/pP65), an increase in IκB kinase (IKK), and a decrease in phosphorylated protein kinase B (p-Akt), respectively. Moreover, more monocytes (2-fold higher for LPS and 15% higher for oxLDL) were attached on LPS/oxLDL-stimulated HUVECs. 5 mM MßCD reversed the LPS/oxLDL-induced changes back to the control levels. CONCLUSIONS: MßCD significantly suppresses the LPS/oxLDL-triggered monocyte-endothelial adhesion by downregulating adhesion molecule expression probably via LPS-IKK-NF-κB or oxLDL-Akt-NF-κB pathway. This study demonstrates a potential mechanism of the anti-atherosclerotic efficacy of cyclodextrin from the angle of monocyte-endothelial adhesion.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34357870

RESUMO

Deep neural networks (DNNs) have achieved great success in many applications. The architectures of DNNs play a crucial role in their performance, which is usually manually designed with rich expertise. However, such a design process is labor-intensive because of the trial-and-error process and also not easy to realize due to the rare expertise in practice. Neural architecture search (NAS) is a type of technology that can design the architectures automatically. Among different methods to realize NAS, the evolutionary computation (EC) methods have recently gained much attention and success. Unfortunately, there has not yet been a comprehensive summary of the EC-based NAS algorithms. This article reviews over 200 articles of most recent EC-based NAS methods in light of the core components, to systematically discuss their design principles and justifications on the design. Furthermore, current challenges and issues are also discussed to identify future research in this emerging field.

8.
Neurocase ; : 1-12, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34455925

RESUMO

In five people with severe dementia, we measured their behavioral and physiological responses to familiar/unfamiliar music and speech, and measured ERP responses to subject's own name (SON) after exposure to familiar/unfamiliar music or noise. We observed more frequent behavioral responses to personally-significant stimuli than non-personally-significant stumuli, and higher skin temperatures for music than non-music conditions. The control group showed typical ERPs to SON, regardless of auditory exposure. ERP measures were unavailable for the dementia group given challenges of measuring EEG in this population. The study highlights the potential for personally-significant auditory stimuli in enhancing responsiveness of people with severe dementia.

9.
Int J Mol Sci ; 22(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34360695

RESUMO

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.


Assuntos
Mucosa Intestinal/metabolismo , Serotonina/metabolismo , Células Enterocromafins/metabolismo , Microbioma Gastrointestinal , Humanos , Intestinos
10.
Biomater Sci ; 9(17): 5951-5964, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34318796

RESUMO

Melanin and its analogue polydopamine (PDA) have attracted considerable attention in biomedical science due to their surface-rich metal binding sites, excellent adhesion and good biocompatibility. Bacterial infections at the wound site and uncontrolled bleeding are associated with a high risk of death, and the prevention of wound infections remains a major challenge. On this basis, the four nanoparticles (NPs) of melanin, PDA, copper ion-loaded melanin (Cu(ii) loaded melanin) and copper ion-loaded PDA (Cu(ii) loaded PDA) were studied in terms of antibacterial and wound healing capabilities. The in vitro experiments showed that Cu(ii) loaded PDA NPs had good blood compatibility and low cytotoxicity, showing the best antibacterial effect in comparison with other samples. Not only could the slow release of copper ions from the nanoparticles kill bacteria, but also the phenolic hydroxyl group and amine groups of PDA NPs played a synergistic role in bacterial death. In wound healing experiments, the Cu(ii) loaded PDA NPs could easily and tightly bind with biological tissue, demonstrating excellent hemostasis, antibacterial and wound healing capabilities. In summary, the excellent properties of Cu(ii) loaded PDA NPs made them a safe and effective drug for preventing wound infection and promoting healing.


Assuntos
Cobre , Nanopartículas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Decapodiformes , Indóis , Tinta , Íons , Melaninas , Polímeros , Cicatrização
11.
Mol Biol Evol ; 38(10): 4116-4134, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34255082

RESUMO

Vestimentiferan tubeworms are iconic animals that present as large habitat-forming chitinized tube bushes in deep-sea chemosynthetic ecosystems. They are gutless and depend entirely on their endosymbiotic sulfide-oxidizing chemoautotrophic bacteria for nutrition. Information on the genomes of several siboglinid endosymbionts has improved our understanding of their nutritional supplies. However, the interactions between tubeworms and their endosymbionts remain largely unclear due to a paucity of host genomes. Here, we report the chromosome-level genome of the vestimentiferan tubeworm Paraescarpia echinospica. We found that the genome has been remodeled to facilitate symbiosis through the expansion of gene families related to substrate transfer and innate immunity, suppression of apoptosis, regulation of lysosomal digestion, and protection against oxidative stress. Furthermore, the genome encodes a programmed cell death pathway that potentially controls the endosymbiont population. Our integrated genomic, transcriptomic, and proteomic analyses uncovered matrix proteins required for the formation of the chitinous tube and revealed gene family expansion and co-option as evolutionary mechanisms driving the acquisition of this unique supporting structure for deep-sea tubeworms. Overall, our study provides novel insights into the host's support system that has enabled tubeworms to establish symbiosis, thrive in deep-sea hot vents and cold seeps, and produce the unique chitinous tubes in the deep sea.

12.
Adv Healthc Mater ; 10(18): e2100590, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34292673

RESUMO

As an important part of tumor microenvironment, tumor associated macrophages (TAMs) play a vital role in the occurrence, development, invasion, and metastasis of many malignant tumors and can significantly promote the formation of tumor blood vessels and lymphatic vessels, hence TAMs are greatly associated with poor prognosis. The research on nanomedicine has achieved huge progress, and nano-drugs have been widely utilized to treat various diseases through different mechanisms. Therefore, developing nano-drugs that are based on TAMs-associated anti-tumor mechanisms to effectively suppress tumor growth is expected to be a promising research filed. This paper introduces relevant information about TAMs in terms of their origin, and their roles in tumor genesis, development and metastasis. Furthermore, TAMs-related anti-tumor nano-drugs are summarized. Specifically, a wide range of nano-drugs targeting at TAMs are introduced, and categorized according to their therapeutic mechanisms toward tumors. Additionally, various nano delivery platforms using TAMs as cell carriers which aim at inhibiting tumor growth are reviewed. These two parts elucidate that the exploration of nanomedicine is essential to the study on TAMs-related anti-tumor strategies. This review is also intended to provide novel ideas for in-depth investigation on anti-tumor molecular mechanisms and nano-drug delivery systems based on TAMs.


Assuntos
Nanomedicina , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Macrófagos Associados a Tumor
13.
Ann Med ; 53(1): 960-970, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34124974

RESUMO

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumour of the head and neck. Our previous study reveals that the circular RNA (circRNA) hsa_circ_0042823 is abnormally expressed in LSCC, suggesting that hsa_circ_0042823 is closely associated with LSCC. Here, we attempted to explore the molecular mechanism of hsa_circ_0042823 in LSCC. METHODS: Quantitative real-time PCR and western blot were performed to assess the expression of gene and protein in human laryngeal carcinoma cells, TU212 and TU686. MTT and transwell assays were performed to examine cell proliferation, migration and invasion. The relationship among hsa_circ_0042823, miR-877-5p and forkhead box M1 (FOXM1) was verified by luciferase reporter assay. Finally, we constructed a subcutaneous tumour mouse model to analyse in vivo growth of LSCC cells following knockdown of hsa_circ_0042823. RESULTS: Compared with normal human bronchial epithelial cells (HBECs), hsa_circ_0042823 was highly expressed in the LSCC cell lines (AMC-HN-8 and TU686). Further studies demonstrated that hsa_circ_0042823 interacted with miR-877-5p, and FOXM1 was the target of miR-877-5p. Hsa_circ_0042823 promoted the expression of FOXM1 via its ceRNA activity on miR-877-5p. Hsa_circ_0042823 overexpression promoted proliferation, migration and invasion of AMC-HN-8 cells through regulating miR-877-5p/FOXM1 axis. Additionally, inhibition of hsa_circ_0042823 inhibited growth of LSCC in vivo via miR-877-5p/FOXM1 axis. CONCLUSIONS: Hsa_circ_0042823/miR-877-5p/FOXM1 axis participates in the progression of LSCC. This work demonstrates that hsa_circ_0042823 accelerates cancer progression by regulating miR-877-5p/FOXM1 axis in LSCC. Therefore, this study may provide new insights into the pathogenesis of LSCC.KEY MESSAGESHsa_circ_0042823 promotes FOXM1 expression by sponging miR-877-5p.Hsa_circ_0042823 promotes proliferation, migration, invasion of LSCC cells.Hsa_circ_0042823 knockdown inhibits tumour growth of LSCC via miR-877-5p/FOXM1 axis.

14.
BMC Cancer ; 21(1): 753, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187411

RESUMO

BACKGROUND: Terminal differentiation-induced ncRNA (TINCR) plays an essential role in epidermal differentiation and is involved in the development of various cancers. METHODS: qPCR was used to detect the expression level of TINCR in tissues and cell lines of laryngeal squamous cell carcinoma (LSCC). The potential targets of TINCR were predicted by the bioinformation website. The expression of miR-210 and BTG2 genes were detected by qPCR, and the protein levels of BTG2 and Ki-67 were evaluated by western blot. CCK-8 assay, scratch test, and transwell chamber were used to evaluate the proliferation, invasion, and metastasis ability of LSCC cells. The relationships among TINCR, miR-210, and BTG2 were investigated by bioinformatics software and luciferase reporter assay. The in vivo function of TINCR was accessed on survival rate and tumor growth in nude mice. RESULTS: We used qRT-PCR to detect the expression of TINCR in laryngeal squamous cell carcinoma (LSCC) tissues and cells and found significantly lower levels in cancer tissues compared with adjacent tissues. Additionally, patients with high TINCR expression had a better prognosis. TINCR overexpression was observed to inhibit the proliferation and invasion of LSCC cells. TINCR was shown to exert its antiproliferation and invasion effects by adsorbing miR-210, which significantly promoted the proliferation and invasion of laryngeal squamous cells. Overexpression of miR-210 was determined to reverse the tumour-suppressive effects of TINCR. BTG2 (anti-proliferation factor 2) was identified as the target gene of miR-210, and BTG2 overexpression inhibited the proliferation and invasion of LSCC cells. BTG2 knockdown relieved the inhibitory effects of TINCR on the proliferation and invasion of LSCC. Finally, TINCR upregulation slowed xenograft tumour growth in nude mice and significantly increased survival compared with control mice. CONCLUSION: The results of this study suggest that TINCR inhibits the proliferation and invasion of LSCC by regulating the miR-210/BTG2 pathway, participates in cell cycle regulation, and may become a target for the treatment of LSCC.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Laríngeas/patologia , Camundongos , Camundongos Nus , Transfecção
15.
Stem Cell Res Ther ; 12(1): 271, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957971

RESUMO

BACKGROUND: Expansion-mediated replicative senescence and age-related natural senescence have adverse effects on mesenchymal stem cell (MSC) regenerative capability and functionality, thus severely impairing the extensive applications of MSC-based therapies. Emerging evidences suggest that microRNA-34a (miR-34a) has been implicated in the process of MSC senescence; however, the molecular mechanisms with regard to how miR-34a influencing MSC senescence remain largely undetermined. METHODS: MiR-34a expression in MSCs was evaluated utilizing RT-qPCR. The functional effects of miR-34a exerting on MSC senescence were investigated via gene manipulation. Relevant gene and protein expression levels were analyzed by RT-qPCR and western blot. Luciferase reporter assays were applied to confirm that Nampt is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting Nampt in MSC senescence was further explored by measuring intracellular NAD+ content, NAD+/NADH ratio and Sirt1 activity. RESULTS: In contrast to Nampt expression, miR-34a expression incremented in senescent MSCs. MiR-34a overexpression in young MSCs resulted in senescence-associated characteristics as displayed by senescence-like morphology, prolonged cell proliferation, declined osteogenic differentiation potency, heightened senescence-associated-ß-galactosidase activity, and upregulated expression levels of the senescence-associated factors. Conversely, miR-34a suppression in replicative senescent and natural senescent MSCs contributed to diminished senescence-related phenotypic features. We identified Nampt as a direct target gene of miR-34a. In addition, miR-34a repletion resulted in prominent reductions in Nampt expression levels, NAD+ content, NAD+/NADH ratio, and Sirt1 activity, whereas anti-miR-34a treatment exerted the opposite effects. Furthermore, miR-34a-mediated MSC senescence was evidently rescued following the co-treatment with Nampt overexpression. CONCLUSION: This study identifies a significant role of miR-34a playing in MSC replicative senescence and natural senescence via targeting Nampt and further mediating by NAD+-Sirt1 pathway, carrying great implications for optimal strategies for MSC therapeutic applications.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Senescência Celular , MicroRNAs/genética , NAD , Osteogênese , Sirtuína 1/genética
16.
Int J Biol Macromol ; 183: 1948-1958, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34051256

RESUMO

Aflatoxin contamination is one of the most important factors jeopardizing the quality of traditional Chinese health food (TCHF) during storage. Based on our previous work, we investigated the stability of chitosan (CH) films containing turmeric essential oil (TEO) and employed CH-TEO films as inner pouches, then stored them with inoculated Coix seed, nutmeg, and Ziziphi Spinosae Semen (ZSS). We found that the stability of CH-TEO was most affected by high temperature, and these pouches dramatically decreased aflatoxin accumulation and maintained levels of marker components of each TCHF. We found that glycerol tristearat in Coix seed and jujuboside A and spinosin in ZSS were negatively correlated with aflatoxin accumulation. After three months of storage with a CH-TEO pouch, we found little change in marker components contents, but observed that Coix seed had the relative lower sensory characteristics score. In addition, acute and 90-day subchronic toxicity test in Coix seed stored with the largest amount of TEO showed no significant signs of toxicity or treatment-related changes in animals. The present study is the first report on the study of a green, efficient, and low toxicity solution for aflatoxic contamination in TCHF, and provides strong support for its future use.


Assuntos
Aflatoxinas/análise , Quitosana/química , Curcuma/química , Óleos Voláteis/química , Ziziphus/química , Animais , Coix/química , Feminino , Contaminação de Alimentos , Armazenamento de Alimentos , Temperatura Alta , Masculino , Camundongos , Myristica/química , Óleos Vegetais/química , Ratos , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Triglicerídeos/química
17.
Aging (Albany NY) ; 13(7): 10584-10602, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33833130

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as the key regulators in the pathogenesis of human disorders. This study aimed to investigate the role of lncRNA-IPW in the progression of choroidal neovascularization (CNV) and the underlying molecular mechanism. IPW was significantly up-regulated in the choroidal tissues of laser-induced CNV mice and in the endothelial cells in response to hypoxic stress. IPW silencing led to reduced formation of CNV in laser-induced CNV model and ex vivo choroidal sprouting model, which could achieve similar therapeutic effects of anti-VEGF on CNV formation. Silencing or transgenic overexpression of IPW could alter endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, IPW silencing led to increased expression of miR-370. Increased miR-370 could mimic the effects of IPW silencing on CNV formation and endothelial angiogenic phenotypes in vivo and in vitro. This study suggests that IPW silencing is a promising strategy for the treatment of neovascular ocular diseases.


Assuntos
Neovascularização de Coroide/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Neovascularização de Coroide/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
Artigo em Inglês | MEDLINE | ID: mdl-33831864

RESUMO

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is diverse in its natural history and responsiveness to treatments. There is an urgent need to generate candidate biomarkers for the stratification and individualization of treatment to avoid overtreatment or inadequate treatment. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been identified as an oncogenic gene in multiple human tumors entitles, and dysregulation of NEAT1 was tightly linked to carcinogenesis and cancer progression. METHODS: One hundred two paraffin samples of LSCC patients were collected. Furthermore, in situ hybridization (ISH), Kaplan-Meier, and MTT were used to analyze the relationship between NEAT1 and the progress of LSCC. RESULTS: In this study, ISH revealed that NEAT1 was strongly expressed in the nucleus. The increased expression of NEAT1 was correlated with T grade, neck nodal metastasis, clinical stage, drinking history, or smoking history of LSCC. The Kaplan-Meier analysis indicated that patients with higher NEAT1 expression had a worse overall survival in LSCC patients. In addition, NEAT1 knockdown significantly inhibited the growth of LSCC cells. CONCLUSION: Together, these results suggested that NEAT1 involved in the progress of LSCC and might act as a tumor oncogenic gene. This study provides a potential new marker and target for gene therapy in the treatment of LSCC.

19.
Pestic Biochem Physiol ; 174: 104823, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33838716

RESUMO

Conventional and volatile pyrethroids are widely used to control the vectors of dengue arboviral diseases, Aedes albopictus in China. The development of resistance to conventional pyrethroids has become an increasing problem, potentially affecting the use of volatile pyrethroid. The Ae. albopictus dimefluthrin-resistant (R) strain by selecting the field population with dimefluthrin were investigated the multiple and cross-resistance levels between conventional and volatile pyrethroids and analyzed both target-site and metabolic resistant mechanisms to dimefluthrin compared with three volatile pyrethroids metofluthrin, meperfluthrin and esbiothrin and type II pyrethroid deltamethrin. The R strain displayed moderate to low resistance to selected pyrethroids (dimefluthrin, metofluthrin, meperfluthrin, esbiothrin and deltamethrin) associated with metabolic enzymes, but less distinctly to selected pyrethroids (dimefluthrin and metofluthrin) associated with a high frequency of sodium channel gene mutation (F1534S). Profiles of the multiple and cross-resistance of the R strain to other three volatile pyrethroids and type II pyrethroid deltamethrin were detected. Both synergistic and enzyme activity studies indicated that multifunctional oxidase (MFO) played an important role in this resistance.


Assuntos
Aedes , Inseticidas , Piretrinas , Aedes/genética , Animais , China , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores , Piretrinas/farmacologia
20.
Exp Mol Pathol ; 120: 104631, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33744280

RESUMO

BACKGROUND: Preeclampsia is a life-threatening hypertensive disorder during pregnancy, while underlying pathogenesis and its diagnosis are incomplete. METHODS: In this study, we utilized the Robust Rank Aggregation method to integrate 6 eligible preeclampsia microarray datasets from Gene Expression Omnibus database. We used linear regression to assess the associations between significant differentially expressed genes (DEGs) and blood pressure. Functional annotation, protein-protein interaction, Gene Set Enrichment Analysis (GSEA) and single sample GSEA were employed for investigating underlying pathogenesis in preeclampsia. RESULTS: We filtered 52 DEGs and further screened for 5 hub genes (leptin, pappalysin 2, endoglin, fms related receptor tyrosine kinase 1, tripartite motif containing 24) that were positively correlated with both systolic blood pressure and diastolic blood pressure. Receiver operating characteristic indicated that hub genes were potential biomarkers for diagnosis and prognosis in preeclampsia. GSEA for single hub gene revealed that they were all closely related to angiogenesis and estrogen response in preeclampsia. Moreover, single sample GSEA showed that the expression levels of 5 hub genes were correlated with those of immune cells in immunologic microenvironment at maternal-fetal interface. CONCLUSIONS: These findings provide new insights into underlying pathogenesis in preeclampsia; 5 hub genes were identified as biomarkers for diagnosis and prognosis in preeclampsia.


Assuntos
Biomarcadores/análise , Biologia Computacional/métodos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Análise em Microsséries/métodos , Pré-Eclâmpsia/patologia , Mapas de Interação de Proteínas , Biomarcadores/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Prognóstico
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