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1.
Complement Ther Clin Pract ; 55: 101849, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522328

RESUMO

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Qualidade de Vida , Estudos Prospectivos , Dispneia
2.
J Clin Nurs ; 33(5): 1976-1994, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38450810

RESUMO

AIM: To identify and appraise the quality of evidence of transitional care interventions on quality of life in lung cancer patients. BACKGROUND: Quality of life is a strong predictor of survival. The transition from hospital to home is a high-risk period for patients' readmission and death, which seriously affect their quality of life. DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and CINAHL databases were searched from inception to 22 October 2022. The primary outcome was quality of life. Statistical analysis was conducted using Review Manager 5.4, results were expressed as standard mean difference (SMD) with a 95% confidence interval (CI). The risk of bias of the included studies was assessed using the Cochrane risk of bias assessment tool. This study was complied with PRISMA guidelines and previously registered in PROSPERO (CRD42023429464). RESULTS: Fourteen randomized controlled trials were included consisting of a total of 1700 participants, and 12 studies were included in the meta-analysis. It was found that transitional care interventions significantly improved quality of life (SMD = 0.21, 95% CI: 0.02 to 0.40, p = .03) and helped reduce symptoms (SMD = -0.65, 95% CI: -1.13 to -0.18, p = .007) in lung cancer patients, but did not significantly reduce anxiety and depression, and the effect on self-efficacy was unclear. CONCLUSIONS: This study shows that transitional care interventions can improve quality of life and reduce symptoms in patients, and that primarily educational interventions based on symptom management theory appeared to be more effective. But, there was no statistically significant effect on anxiety and depression. RELEVANCE TO CLINICAL PRACTICE: This study provides references for the application of transitional care interventions in the field of lung cancer care, and encourages nurses and physicians to apply transitional care plans to facilitate patients' safe transition from hospital to home. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.


Assuntos
Neoplasias Pulmonares , Cuidado Transicional , Humanos , Qualidade de Vida , Neoplasias Pulmonares/terapia , Ansiedade , Transtornos de Ansiedade
3.
J Control Release ; 367: 354-365, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286337

RESUMO

Synergistic photothermal immunotherapy has attracted widespread attention due to the mutually reinforcing therapeutic effects on primary and metastatic tumors. However, the lack of clinical approval nanomedicines for spatial, temporal, and dosage control of drug co-administration underscores the challenges facing this field. Here, a photothermal agent (Cy7-TCF) and an immune checkpoint blocker (NLG919) are conjugated via disulfide bond to construct a tumor-specific small molecule prodrug (Cy7-TCF-SS-NLG), which self-assembles into prodrug-like nano-assemblies (PNAs) that are self-delivering and self-formulating. In tumor cells, over-produced GSH cleaves disulfide bonds to release Cy7-TCF-OH, which re-assembles into nanoparticles to enhance photothermal conversion while generate reactive oxygen species (ROSs) upon laser irradiation, and then binds to endogenous albumin to activate near-infrared fluorescence, enabling multimodal imaging-guided phototherapy for primary tumor ablation and subsequent release of tumor-associated antigens (TAAs). These TAAs, in combination with the co-released NLG919, effectively activated effector T cells and suppressed Tregs, thereby boosting antitumor immunity to prevent tumor metastasis. This work provides a simple yet effective strategy that integrates the supramolecular dynamics and reversibility with stimuli-responsive covalent bonding to design a simple small molecule with synergistic multimodal imaging-guided phototherapy and immunotherapy cascades for cancer treatment with high clinical value.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/uso terapêutico , Nanomedicina Teranóstica , Neoplasias/terapia , Fototerapia , Nanopartículas/química , Antígenos de Neoplasias , Imunoterapia , Dissulfetos , Linhagem Celular Tumoral
4.
J Prosthodont Res ; 68(2): 193-205, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37302842

RESUMO

PURPOSE: The surge in digitalization and artificial intelligence has led to the wide application of robots in various fields, but their application in dentistry started relatively late. This scoping review aimed to comprehensively explore and map the current status of the clinical application of robots in dentistry. STUDY SELECTION: An iterative approach was used to gather as much evidence as possible from four online databases, including PubMed, the China National Knowledge Infrastructure, the Japan Science and Technology Information Aggregator, Electronic, and the Institute of Electrical and Electronics Engineers, from January 1980 to December 2022. RESULTS: A total of 113 eligible articles were selected from the search results, and it was found that most of the robots were developed and applied in the United States (n = 56; 50%). Robots were clinically applied in oral and maxillofacial surgery, oral implantology, prosthodontics, orthodontics, endodontics, and oral medicine. The development of robots in oral and maxillofacial surgery and oral implantology is relatively fast and comprehensive. About 51% (n = 58) of the systems had reached clinical application, while 49% (n = 55) were at the pre-clinical stage. Most of these are hard robots (90%; n = 103), and their invention and development were mainly focused on university research groups with long research periods and diverse components. CONCLUSIONS: There are still limitations and gaps between research and application in dental robots. While robotics is threatening to replace clinical decision-making, combining it with dentistry to gain maximum benefit remains a challenge for the future.


Assuntos
Medicina Bucal , Robótica , Cirurgia Bucal , Humanos , Inteligência Artificial , Prostodontia
5.
Poult Sci ; 103(1): 103242, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37980746

RESUMO

Heat stress in chickens caused by high temperatures in summer is a serious issue faced by the poultry industry globally, which reduces product quality. The aim of this study is to investigate the role of resveratrol in alleviating heat stress injury and inflammatory response of jejunal mucosa in black-boned chickens through TLR4/MAPK signaling pathway. In total, 240 black-boned chickens (28-day old) were randomly divided into 4 treatment groups as follows. The normal temperature (NT) and normal temperature with resveratrol (NT+Res) groups received a basal diet without and with 400 mg/kg resveratrol, respectively, and treated at 24℃ ± 2℃, 24 h/d. The high temperature (HT) and high temperature with resveratrol (HT+Res) groups received basal diet without and with 400 mg/kg resveratrol, respectively, and treated at 37℃ ± 2℃ for 8 h/d and 24°C ± 2°C for the rest of the time for 12 d. The results revealed the heat-stress responses impaired the villous structure of the jejunum, causing a rough and uneven surface of the jejunal villus, and local intestinal villi were even more prone to rupture. However, resveratrol significantly improved the morphology and structure of jejunal mucosa under heat stress. Heat stress increased the mRNA levels of toll-like receptor 4 (TLR4), c-Jun, c-fos, caspase-3, and p38 (P < 0.05), reduced mRNA level of Bcl-2, and reduced the expression of tight junction proteins Occludin, ZO-1, and Claudin1 (P < 0.05) in the jejunal mucosa. However, resveratrol inhibited the TLR4/ mitogen-activated protein kinase (MAPK) signaling pathway via downregulating TLR4, c-Jun, p38, and caspase-3 (P < 0.05); upregulating Bcl-2 (P < 0.05); decreasing the protein levels of MKK3, p53, and myeloid differentiation factor 88 (MYD88); and increasing the protein levels of Occludin, ZO-1, and Claudin1. In addition, it reduced the levels of JNK and p38 proteins (P < 0.05) and inflammatory factors like tumor necrosis factor-α (TNF-α) in the jejunal mucosa of black-boned chickens under heat stress. In conclusion, resveratrol may play a regulatory role in heat-stress-induced damage and inflammatory response in the intestinal mucosa of black-boned chickens under heat stress.


Assuntos
Galinhas , Jejuno , Animais , Resveratrol/farmacologia , Resveratrol/metabolismo , Galinhas/fisiologia , Jejuno/metabolismo , Caspase 3/metabolismo , Ocludina/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Mucosa Intestinal/metabolismo , Resposta ao Choque Térmico , Transdução de Sinais , RNA Mensageiro/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
6.
Molecules ; 28(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138447

RESUMO

Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1-2) and seventeen known compounds (3-19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 µM. In addition, compounds 1-2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.


Assuntos
Ampelopsis , Antioxidantes , Inibidores de Glicosídeo Hidrolases , alfa-Glucosidases , Ampelopsis/química , Antioxidantes/farmacologia , Antioxidantes/química , Flavonoides/química , Extratos Vegetais/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia
7.
Vaccines (Basel) ; 11(12)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38140181

RESUMO

Avian pathogenic Escherichia coli (APEC) is one of the leading pathogens that cause devastating economic losses to the poultry industry. Type I fimbriae are essential adhesion factors of APEC, which can be targeted and developed as a vaccine candidate against multiple APEC serogroups due to their excellent immunogenicity and high homology. In this study, the recombinant strain SG102 was developed by expressing the APEC type I fimbriae gene cluster (fim) on the cell surface of an avirulent Salmonella gallinarum (S. gallinarum) vector strain using a chromosome-plasmid-balanced lethal system. The expression of APEC type I fimbriae was verified by erythrocyte hemagglutination assays and antigen-antibody agglutination tests. In vitro, the level of the SG102 strain adhering to leghorn male hepatoma (LMH) cells was significantly higher than that of the empty plasmid control strain, SG101. At two weeks after oral immunization, the SG102 strain remained detectable in the livers, spleens, and ceca of SG102-immunized chickens, while the SG101 strain was eliminated in SG101-immunized chickens. At 14 days after the secondary immunization with 5 × 109 CFU of the SG102 strain orally, highly antigen-specific humoral and mucosal immune responses against APEC type I fimbriae protein were detected in SG102-immunized chickens, with IgG and secretory IgA (sIgA) concentrations of 221.50 µg/mL and 1.68 µg/mL, respectively. The survival rates of SG102-immunized chickens were 65% (13/20) and 60% (12/20) after challenge with 50 LD50 doses of APEC virulent strains O78 and O161 serogroups, respectively. By contrast, 95% (19/20) and 100% (20/20) of SG101-immunized chickens died in challenge studies involving APEC O78 and O161 infections, respectively. In addition, the SG102 strain effectively provided protection against lethal challenges from the virulent S. gallinarum strain. These results demonstrate that the SG102 strain, which expresses APEC type I fimbriae, is a promising vaccine candidate against APEC O78 and O161 serogroups as well as S. gallinarum infections.

8.
Signal Transduct Target Ther ; 8(1): 417, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37907503

RESUMO

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.


Assuntos
Menisco , Transplante de Células-Tronco Mesenquimais , Animais , Humanos , Coelhos , Diferenciação Celular , Matriz Extracelular , Transplante de Células-Tronco Mesenquimais/métodos
9.
ACS Macro Lett ; 12(11): 1583-1588, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37937586

RESUMO

Hydrogen sulfide (H2S) is an important gaseous signaling molecule with unique pleiotropic pharmacological effects, but may be limited for clinical translation due to the lack of a reliable delivery form that delivers exogenous H2S to cells at action site with precisely controlled dosage. Herein, we report the design of a poly(thiourethane) (PTU) self-immolative polymer terminally caged with an acrylate moiety to trigger release of H2S in response to cysteine (Cys) and homocysteine (Hcy), the most used and independent indicators of neurodegenerative diseases. The synthesized PTU polymer was then coated with the red-blood-cell (RBC) membrane in the presence of solubilizing agent to self-assemble into nanoparticles with enhanced stability and cytocompatibility. The Hcy/Cys mediated addition/cyclization chemistry actuated the biomimetic polymeric nanoparticles to disintegrate into carbonyl sulfide (COS), and finally convert into H2S via the ubiquitous carbonic anhydrase (CA). H2S released in a controlled manner exhibited a strong antioxidant ability to resist Alzheimer's disease (AD)-related oxidative stress factors in BV-2 cells, a neurodegenerative disease model in vitro. Thus, this work may provide an effective strategy to construct H2S donors that can degrade in response to a specific pathological microenvironment for the treatment of neurodegenerative diseases.


Assuntos
Sulfeto de Hidrogênio , Doenças Neurodegenerativas , Humanos , Cisteína , Sulfeto de Hidrogênio/química , Membrana Eritrocítica/metabolismo , Polímeros
10.
Angew Chem Int Ed Engl ; 62(45): e202307664, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37718311

RESUMO

Protein therapeutics targeting intracellular machineries hold profound potential for disease treatment, and hence robust cytosolic protein delivery technologies are imperatively demanded. Inspired by the super-negatively charged, nucleotide-enriched structure of nucleic acids, adenylated pro-proteins (A-proteins) with dramatically enhanced negative surface charges have been engineered for the first time via facile green synthesis. Then, thymidine-modified polyethyleneimine is developed, which exhibits strong electrostatic attraction, complementary base pairing, and hydrophobic interaction with A-proteins to form salt-resistant nanocomplexes with robust cytosolic delivery efficiencies. The acidic endolysosomal environment enables traceless restoration of the A-proteins and consequently promotes the intracellular release of the native proteins. This strategy shows high efficiency and universality for a variety of proteins with different molecular weights and isoelectric points in mammalian cells. Moreover, it enables highly efficient delivery of CRISPR-Cas9 ribonucleoproteins targeting fusion oncogene EWSR1-FLI1, leading to pronounced anti-tumor efficacy against Ewing sarcoma. This study provides a potent and versatile platform for cytosolic protein delivery and gene editing, and may benefit the development of protein pharmaceuticals.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Animais , Pareamento de Bases , Proteínas/genética , Endossomos , Mamíferos
11.
BMC Med Educ ; 23(1): 574, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582729

RESUMO

BACKGROUND: Simulation-based medical education (SBME) and three-dimensional printed (3DP) models are increasingly used in continuing medical education and clinical training. However, our understanding of their role and value in improving trainees' understanding of the anatomical and surgical procedures associated with liver surgery remains limited. Furthermore, gender bias is also a potential factor in the evaluation of medical education. Therefore, the aim of this study was to evaluate the educational benefits trainees receive from the use of novel 3DP liver models while considering trainees' experience and gender. METHODS: Full-sized 3DP liver models were developed and printed using transparent material based on anonymous CT scans. We used printed 3D models and conventional 2D CT scans of the liver to investigate thirty trainees with various levels of experience and different genders in the context of both small group teaching and formative assessment. We adopted a mixed methods approach involving both questionnaires and focus groups to collect the views of different trainees and monitors to assess trainees' educational benefits and perceptions after progressing through different training programs. We used Objective Structured Clinical Examination (OSCE) and Likert scales to support thematic analysis of the responses to the questionnaires by trainees and monitors, respectively. Descriptive analyses were conducted using SPSS statistical software version 21.0. RESULTS: Overall, a 3DP model of the liver is of great significance for improving trainees' understanding of surgical procedures and cooperation during operation. After viewing the personalized full-sized 3DP liver model, all trainees at the various levels exhibited significant improvements in their understanding of the key points of surgery (p < 0.05), especially regarding the planned surgical procedure and key details of the surgical procedures. More importantly, the trainees exhibited higher levels of satisfaction and self-confidence during the operation regardless of gender. However, with regard to gender, the results showed that the improvement of male trainees after training with the 3DP liver model was more significant than that of female trainees in understanding and cooperation during the surgical procedure, while no such trend was found with regard to their understanding of the base knowledge. CONCLUSION: Trainees and monitors agreed that the use of 3DP liver models was acceptable. The improvement of the learning effect for practical skills and theoretical understanding after training with the 3DP liver models was significant. This study also indicated that training with personalized 3DP liver models can improve all trainees' presurgical understanding of liver tumours and surgery and males show more advantage in understanding and cooperation during the surgical procedure as compared to females. Full-sized realistic 3DP models of the liver are an effective auxiliary teaching tool for SBME teaching in Chinese continuing medical education.


Assuntos
Neoplasias , Sexismo , Humanos , Feminino , Masculino , Fígado/diagnóstico por imagem , Fígado/cirurgia , Abdome , Impressão Tridimensional
12.
Nanoscale Adv ; 5(15): 3994-4001, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37496625

RESUMO

Endometriosis is a tumor-like disease with high recurrence. In this case, the accurate imaging-based diagnosis of endometriosis can help clinicians eradicate it by improving their surgical plan. However, although contrast agents can improve the visibility of the tissue of interest in vivo via magnetic resonance imaging (MRI), the lack of biomarkers in endometriosis hinders the development of agents for its targeted imaging and diagnosis. Herein, aiming at the enriched vascular endothelial growth factor (VEGF) in endometriosis, we developed a targeting MRI contrast agent modified with bevacizumab, i.e., NaGdF4@PEG@bevacizumab-Cy5.5 nanoparticles (NPBCNs), to detect endometriosis. NPBCNs showed negligible cytotoxicity and high affinity towards VEGF in endometrial cells in vitro. Furthermore, NPBCNs generated a strong signal enhancement in vivo in endometriosis lesions in rats in T1-weighted images via MRI at 3 days post-injection, as confirmed by the histopathological staining results and fluorescence imaging on the same day. Our approach can enable NPBCNs to target endometriosis effectively, thus avoiding missed diagnoses.

13.
Aging Male ; 26(1): 2205935, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37162757

RESUMO

OBJECTIVE: To report an extremely rare case of bladder cancer patient with cervical lymph nodes, abdominal lymph nodes, and bone metastases at the same time. METHODS AND RESULTS: The case was investigated by follow-up and immunohistochemistry was used in the pathological part. RESULT: The patient was diagnosed with bladder cancer (high-grade urothelial metastatic epithelial cell carcinoma) by pathology and immunohistochemistry after transurethral resection of bladder tumor (TURBT) and metastatic bladder cancer by pathology and immunohistochemistry after cervical lymph node aspiration due to neck lymph node enlargement 1 year later, and a CT of the chest and abdomen suggested that the patient also had abdominal lymph node and bone metastases.At the 2.5-year regular chemotherapy follow-up, the patient showed that the abdominal lymph node metastasis disappeared, the cervical lymph node fusion shrank, and the bone metastasis still existed. CONCLUSION: 1. Regular postoperative review is particularly important; 2.For patients with UCB who undergo TURBT, a effective regular perfusion program should be performed throughout the postoperative period; 3. For patients with postoperative metastatic symptoms of UCB, Complex treatment has a positive effect on patient prognosis; 4.The presence of enlarged head and neck lymph nodes in patients with bladder cancer should also be considered as metastatic of UCB.


Assuntos
Linfonodos , Neoplasias da Bexiga Urinária , Humanos , Metástase Linfática , Linfonodos/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Prognóstico
14.
Genes (Basel) ; 14(5)2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37239411

RESUMO

The role of lncRNA in cancer development has received more and more attention in research. A variety of lncRNAs are associated with the occurrence and development of glioma. However, the role of TRHDE-AS1 in glioma is still unknown. In this study, we explored the role of TRHDE-AS1 in glioma through bioinformatic methods. We first identified an association between TRHDE-AS1 and tumor prognosis in pan-cancer analysis. Subsequently, the expression levels of TRHDE-AS1 in various clinical types of glioma were compared, and significant differences were found in pathological classification, WHO classification, molecular classification, IDH mutation, and age stratification. We analyzed the genes co-expressed with TRHDE-AS1 in glioma. In the functional analysis of TRHDE-AS1, we found that TRHDE-AS1 may be involved in the regulation of synapse-related functions. In glioma cancer driver gene correlation analysis, it was also found that TRHDE-AS1 was significantly correlated with the expression levels of multiple driver genes such as TP53, BRAF, and IDH1. By comparing the mutant profiles of the high and low TRHDE-AS1 groups, we also found that there may be differences in TP53 and CIC gene mutations in low-grade gliomas. Subsequent correlation analysis between TRHDE-AS1 and glioma immune microenvironment showed that the expression level of TRHDE-AS1 was correlated with a variety of immune cells. Therefore, we believe that TRHDE-AS1 is involved in the occurrence and development of glioma and has the ability to predict the prognosis of glioma as a biomarker of glioma.


Assuntos
Glioma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Glioma/genética , Glioma/patologia , Oncogenes , Prognóstico , Genômica , Microambiente Tumoral
15.
Mol Neurobiol ; 60(9): 5090-5101, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37249790

RESUMO

The prevention of protein condensates has emerged as a new drug target to treat diverse neurodegenerative disorders. We previously reported that terazosin (TZ), a prescribed antagonist of the α1 adrenergic receptor, is an activator of phosphoglycerate kinase 1 (Pgk1) and Hsp90. In this study, we aimed to determine whether TZ prevents the formation of diverse pathological condensates in cell cultures and animal disease models. In primary neuron culture, TZ treatment reduced both the protein density and abundance of fused in sarcoma (FUS)-P525L-GFP, a disease-associated mutant form of FUS. Regarding the mechanism, we found that increased intracellular ATP levels were critical for the reduction in protein aggregate density. In addition, Hsp90 activation by TZ enhanced Hsp90 interaction with ULK1, a master regulator of autophagy. Through in vivo studies, we examined neuron-specific overexpression of tau in Drosophila, mouse models of APP/PS1 Alzheimer's disease (AD), and a rat model of multiple system atrophy (MSA) via the viral expression of α-synuclein in the striatum. TZ prevented and reversed the formation of pathological protein condensates. Together, our results suggest that activation of Pgk1 in cytosol may dissolve pathological protein aggregates via increased ATP levels and degrade these proteins via autophagy; the FUS-P525L degradation pathway in nucleus is unclear.


Assuntos
Doença de Alzheimer , Atrofia de Múltiplos Sistemas , Camundongos , Ratos , Animais , Agregados Proteicos , Doença de Alzheimer/patologia , Neurônios/metabolismo , Atrofia de Múltiplos Sistemas/metabolismo , Trifosfato de Adenosina/metabolismo
16.
Mol Pharm ; 20(5): 2376-2388, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36988290

RESUMO

A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.


Assuntos
Grafite , Neoplasias , Masculino , Camundongos , Feminino , Animais , Grafite/toxicidade , Motilidade dos Espermatozoides , Sêmen , Reprodução , Núcleo Celular
17.
Acad Radiol ; 30 Suppl 2: S220-S226, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624022

RESUMO

RATIONALE AND OBJECTIVES: The purpose of this study was to explore the feasibility of magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) for the treatment of an adenomyosis model of Bama pigs and the changes in the level of oxytocin receptor (OTR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) in the myometrium tissues of Bama pigs after MRgFUS. MATERIALS AND METHODS: Three Bama pig models of adenomyosis were established by autologous endometrial implantation and evaluated by magnetic resonance imaging, computed tomography, and hematoxylin-eosin (H&E) staining. After the successful construction of the model, the pigs underwent MRgFUS. Before the modeling surgery, three months after the modeling, and two months after ablation, the myometrium tissues were clipped, then embedded and H&E stained for immunohistochemical examination. The average optical density of OTR, VEGF, and COX-2 were semi-quantitatively analyzed. RESULTS: The adenomyosis models were established in all Bama pigs and confirmed by magnetic resonance imaging, computed tomography and H&E staining. Magnetic resonance imaging and computed tomography examination showed that the uterine wall at the modeling site was significantly thickened with uneven enhancement after contrast injection. All Bama pigs with adenomyosis lesions underwent MRgFUS without complications. The expression level of OTR and COX-2 in the myometrium increased three months after modeling surgery and decreased two months after MRgFUS. The expression level of VEGF decreased two months after MRgFUS. CONCLUSION: Autologous endometrial implantation is effective in establishing the adenomyosis model of Bama pigs. It is feasible to treat adenomyosis in the Bama pig model with MRgFUS. The levels of OTR, COX-2 and VEGF in the local myometrium decreased after MRgFUS, which may be associated with symptom relief after treatment.


Assuntos
Adenomiose , Procedimentos Cirúrgicos Ultrassônicos , Humanos , Feminino , Animais , Suínos , Adenomiose/diagnóstico por imagem , Adenomiose/cirurgia , Adenomiose/complicações , Fator A de Crescimento do Endotélio Vascular , Ciclo-Oxigenase 2 , Imageamento por Ressonância Magnética
18.
Molecules ; 29(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38202728

RESUMO

Aromatic plants of the family Lamiaceae, especially of the genus Thymus, have promising antioxidant applications in pharmacology, medicine, food, cosmetology, and aromatherapy. Hydrosols (HDs) were extracted by hydrodistillation from seven species of Lamiaceae, including Thymus vulgaris, Thymus mongolicus, Mentha × piperita, Melissa officinalis, Rosmarinus officinali, Salvia elegans, and Leonurus artemisia. In total, 369 volatile components were determined and analyzed by gas chromatography-mass spectrometry (GC-MS). Among them, alcohols (2.86-28.48%), ethers (2.46-10.69%), and phenols (0.11-21.78%) constituted a large proportion, mainly linalool (0.28-19.27%), eucalyptol (0.16-6.97%), thymol (0-19.54%), and carvacrol (0-26.82%). Multivariate statistical analyses were performed and 27 differential metabolites were screened. Three different methods (ABTS+•, DPPH•, and FRAP) were used to determine the in vitro antioxidant activity of seven HDs. Thymus vulgaris hydrosols (Tv HDs) and Thymus mongolicus hydrosols (Tm HDs) had the strongest antioxidant activity and their stronger antioxidant capacity was related to their high levels of phenolic constituents, mainly thymol. The antioxidant activity of the other five Lamiaceae HDs was associated with their high alcohol (mainly linalool and eucalyptol) content, and the alcohol constituents may synergistically affect their antioxidant capacity. Therefore, the present study suggests that Lamiaceae plants can be utilized as antioxidant products or antioxidants in different industrial sectors including pharmaceuticals, food, cosmetics, and agrochemicals.


Assuntos
Monoterpenos Acíclicos , Salvia , Thymus (Planta) , Antioxidantes/farmacologia , Eucaliptol , Timol/farmacologia , Mentha piperita
19.
Ann Med ; 54(1): 2975-2989, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36286390

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a condition of the female reproductive system and it remains imperative to identify target genes responsible for its pathogenesis and develop therapeutic drugs capable of effectively treating it. METHODS: We performed primary screening, staging, functional analysis as well as screening of target genes and therapeutic drugs based on single cell sequencing data of 34 oocytes from the GEO database. RESULTS: Oxidative phosphorylation played a pivotal role in the development of oocytes, insulin resistance and ovulation disorders. At the cellular level, GV and MI phases were particularly critical for the biology of pregnancy. We screened PGR, SIRT1 and ADAMTS1 as hub differentially expressed genes (DEGs) and found relevant drugs using the Drug-Gene Interaction Database. In clinical study, oral contraceptives and insulin sensitisers were found to be effective in the treatment of PCOS. CONCLUSION: PGR, SIRT1 and ADAMTS1 were found to be down-regulated in oocytes, ovulation and female pregnancy. These 3 genes are likely biomarkers important in the treatment of PCOS. Insulin sensitiser in combination with oral contraceptive administration were found to significantly improve PCOS.Key messagesOur study used a new bioinformatics approach to find target genes for the treatment of PCOS.Our study sought to identify target genes that affect human oocyte quality by analysing single-cell sequencing data from oocytes.We testified to our data by analysing a subset of clinical data.


Assuntos
Insulinas , Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/diagnóstico , Sirtuína 1 , Biomarcadores , Anticoncepcionais Orais
20.
Front Oncol ; 12: 987026, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263211

RESUMO

Objective: To present the global research features and hotspots, and forecast the emerging trends by conducting a bibliometric analysis based on literature related to autophagy of pancreatic cancer from 2011 to 2022. Methods: The literature data regarding autophagy of pancreatic cancer were retrieved and downloaded from the Web of Science Core Collection (WOSCC) from Clarivate Analytics on June 10th, 2022. VOSviewer (version 1.6.18) was used to perform the bibliometric analysis. Results: A total of 616 studies written by 3993 authors, covered 45 countries and 871 organizations, published in 263 journals and co-cited 28152 references from 2719 journals. China (n=260, 42.2%) and the United States (n=211, 34.3%) were the most frequent publishers and collaborated closely. However, publications from China had a low average number of citations (25.35 times per paper). The output of University of Texas MD Anderson Cancer Center ranked the first with 26 papers (accounting for 4.2% of the total publications). Cancers (n=23, 3.7%; Impact Factor = 6.639) published most papers in this field and was very pleasure to accept related researches. Daolin Tang and Rui Kang published the most papers (n=18, respectively). The research hotspots mainly focused on the mechanisms of autophagy in tumor onset and progression, the role of autophagy in tumor apoptosis, and autophagy-related drugs in treating pancreatic cancer (especially combined therapy). The emerging topics were chemotherapy resistance mediated by autophagy, tumor microenvironment related to autophagy, autophagy-depended epithelial-mesenchymal transition (EMT), mitophagy, and the role of autophagy in tumor invasion. Conclusion: Attention has been increasing in autophagy of pancreatic cancer over the past 12 years. Our results undoubtedly provide scholars with new clues and ideas in this field.

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