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1.
Genes Dis ; 11(4): 100987, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38560498

RESUMO

Cancer occurrence and development are closely related to increased lipid production and glucose consumption. Lipids are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition, signal transduction, and energy supply, which are vital for cancer cell rapid proliferation, invasion, and metastasis. Sterol regulatory element-binding transcription factor 1 (SREBP1) is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis, lipid homeostasis, and fatty acid synthesis. In addition, SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases, particularly cancer. However, no review of SREBP1 in cancer biology has yet been published. Herein, we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells, including SREBP1 modification, lipid metabolism and reprogramming, glucose and mitochondrial metabolism, immunity, and tumor microenvironment, epithelial-mesenchymal transition, cell cycle, apoptosis, and ferroptosis. Additionally, we discussed the potential role of SREBP1 in cancer prognosis, drug response such as drug sensitivity to chemotherapy and radiotherapy, and the potential drugs targeting SREBP1 and its corresponding pathway, elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

2.
PeerJ ; 12: e17090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38563007

RESUMO

Background: Appearance anxiety and depression have become common and global public health problems worldwide, especially among adolescents. However, few studies have revealed the mechanisms between them. This study aimed to explore the multiple mediating roles of interpersonal sensitivity and social support between appearance anxiety and depression among medical college students. Methods: With 13 invalid samples excluded, 724 college students participated in our survey and completed questionnaires. The average age of 724 samples was 19.8 ± 2.02 including freshman to senior year and graduate school and above; 31.9% of the participants were male and 68.1% were female. SPSS 25.0 and Hayes' PROCESS macro were used for statistical description, correlation analysis and built multiple mediation models. Results: Appearance anxiety can not only directly affect depression, but also indirectly affect depression through three significant mediating pathways: (1) IS (B = 0.106, 95% CI [0.082-0.132]), which accounted for 49.77% of the total effect, (2) SS (B = 0.018, 95% CI [0.008-0.031]), which accounted for 8.45% of the total effect, and (3) IS and SS (B = 0.008, 95% CI [0.003-0.014]), which accounted for 3.76% of the total effect. And the total mediating effect was 61.97%. Limitations: It is a cross-sectional research method and the causal relationship is unclear. Conclusions: This study found that lower interpersonal sensitivity and higher social support can effectively reduce depression caused by appearance anxiety among college students. The schools and relevant departments should take measures to reduce the interpersonal sensitivity of college students and establish reliable social support, so as to reduce the occurrence of depression.


Assuntos
Depressão , Estudantes de Medicina , Adolescente , Humanos , Masculino , Feminino , Depressão/epidemiologia , Universidades , Estudos Transversais , Ansiedade/epidemiologia
3.
Biochem Cell Biol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567768

RESUMO

Cell-in-cell (CIC) structures have been suggested to mediate intracellular substance transport between cells and have been found widely in inflammatory lung tissue of asthma. The aim of this study was to investigate the significance of CIC structures in inflammatory progress of asthma. CIC structures and related inflammatory pathways were analyzed in asthmatic lung tissue and normal lung tissue of mouse model. In vitro, the activation of inflammatory pathways by CIC-mediated intercellular communication was analyzed by RNA-Seq and verified by Western blotting and immunofluorescence. Results showed that CIC structures of lymphocytes and alveolar epithelial cells in asthmatic lung tissue mediated intercellular substance (such as mitochondria) transfer and promoted pro-inflammation in two phases. At early phase, internal lymphocytes triggered inflammasome-dependent pro-inflammation and cell death of itself. Then, degraded lymphocytes released cellular contents such as mitochondria inside alveolar epithelial cells, further activated multi-pattern-recognition receptors and NF-kappa B signaling pathways of alveolar epithelial cells, and thereby amplified pro-inflammatory response in asthma. Our work supplements the mechanism of asthma pro-inflammation progression from the perspective of CIC structure of lymphocytes and alveolar epithelial cells, and provides a new idea for anti-inflammatory therapy of asthma.

4.
J Ultrasound Med ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563453

RESUMO

OBJECTIVES: Ultrasound-targeted microbubble disruption (UTMD) is a widely used technique to improve the differentiation and proliferation capacity of mesenchymal stem cells (MSCs), but the optimal therapeutic parameters for UTMD are unclear. In this study, we aimed to find the appropriate peak negative pressure (PNP), which is a key parameter for enhancing the stemness properties and proliferation of MSCs. METHODS: Experiments were performed in UTMD group, ultrasound (US) group under different PNP exposure conditions (0.5, 1.0, and 1.5 MPa), and control group. Apoptosis safety was analyzed by flow cytometry and MSC proliferation was measured at 12, 24, and 36 hours after irradiation by cell counting kit 8. The expression of the stemness genes NANOG, OCT-4, and SOX-2 were determined by enzyme-linked immunosorbent assay (ELISA) or reverse transcription polymerase chain reaction. RESULTS: The results showed that the 1.5 MPa UTMD-treated group had the highest proliferation capacity of MSCs at 24 hours. ELISA or quantitative reverse transcription polymerase chain reaction results showed that UTMD treatment of the 1.5 MPa group significantly upregulated the expression of the stemness genes NANOG, SOX-2, and OCT-4. CONCLUSIONS: In conclusion, the appropriate peak PNP value of UTMD was 1.5 MPa, and 1.5 MPa-mediated UTMD group obviously promoted MSCs proliferation and maintained stemness by upregulating the expression of stemness genes.

5.
BMC Ophthalmol ; 24(1): 146, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38566099

RESUMO

BACKGROUND: Trauma-induced orbital blowout fracture (OBF) with eyeball displacement into the maxillary sinus is rare. CASE PRESENTATION: We present the case of a 14-year-old with a closed head injury, OBF, and displacement of the eyeball into the maxillary sinus following a car accident. A prompt transconjunctival access surgery was performed for eyeball repositioning and orbital reconstruction in a single session, mitigating anaesthesia-related risks associated with multiple surgeries. At the 12-month follow-up, his visual acuity was 20/200. Despite limited eye movement and optic nerve atrophy, overall satisfaction with the ocular appearance was achieved. CONCLUSIONS: This report offers novel insights into the mechanisms of OBF occurrence and the development of postoperative complications.


Assuntos
Traumatismos Cranianos Fechados , Transtornos da Motilidade Ocular , Fraturas Orbitárias , Masculino , Humanos , Adolescente , Seio Maxilar , Olho , Fraturas Orbitárias/complicações , Fraturas Orbitárias/diagnóstico , Fraturas Orbitárias/cirurgia , Traumatismos Cranianos Fechados/complicações
6.
Schizophr Bull ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38577952

RESUMO

BACKGROUND AND HYPOTHESIS: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. STUDY DESIGN: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. STUDY RESULTS: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). CONCLUSIONS: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

8.
J Sci Food Agric ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629663

RESUMO

BACKGROUND: Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation and purification. OP is associated with immunomodulatory effects, but the underlying mechanisms are not known. Therefore, this study combined 1H-NMR urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. RESULTS: OP can restored the body weight and the structure of spleen and thymus in cyclophosphamide-induced immunosuppression rats. OP upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as IL-6 and TNF-α, and the numbers of CD3+ and CD4+ T cells in the immunosuppression rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urinary, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally combining metabolomics and microbiomics found that taurine an hypotaurine metabolism, also alanine, aspartate and glutamate metabolish were disturbed, but these metabolic pathways were restored by OP. CONCLUSION: This study demonstrated that OP had immunoprotective effects in cyclophosphamide-induced immunosuppression rats by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provides a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. This article is protected by copyright. All rights reserved.

9.
Future Microbiol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629898

RESUMO

Objective: This study investigates the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of neurobrucellosis (NB). Methods: We retrospectively analyzed patients diagnosed with NB who underwent cerebrospinal fluid (CSF) mNGS testing in Xijing Hospital from 2015 to 2021. Results: Among the 20 individuals included in the study, the serum rose bengal test was positive in 11 out of 16 cases, serum agglutination test was positive in 13 out of 16 cases, CSF culture was positive in 6 out of 11 cases, and CSF mNGS tests were positive in 18 out of 20 cases. Conclusion: CSF mNGS demonstrates superior sensitivity; therefore, it is recommended to collect CSF for mNGS testing prior to antibiotic therapy when NB is suspected.


Neurobrucellosis (NB) is a disease of the nervous system caused by a type of bacteria called Brucella. It is rare, serious and manifests inconsistently, making it hard to diagnose. Metagenomic next-generation sequencing (mNGS) is a new way to detect disease-causing bacteria by looking at their genetic material. mNGS is fast, accurate and covers a wide range of disease-causing bacteria. We looked back at patients diagnosed with NB at Xijing Hospital between 2015 and 2021 and tested samples of the fluid surrounding the brain and the spinal cord, called cerebrospinal fluid (CSF), by mNGS. A total of 20 patients were included in the study. Compared with the traditional methods, mNGS of CSF samples showed advantages in diagnosing NB. However, antibiotics may affect the results.

10.
Diagn Pathol ; 19(1): 56, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570882

RESUMO

BACKGROUND: Müllerian adenosarcoma, a rare malignancy, presents diagnostic and therapeutic challenges. In this study, we conducted an analysis of the clinicopathological characteristics of 22 adenosarcomas, with a particular focus on screening for DICER1 hot mutations. METHODS: The cohort consisted of patients with adenosarcoma who were registered at the West China Second Hospital between the years 2020 and June 2022. Sanger sequencing was employed to screen for somatic Hotspot mutations in the RNase IIIb domain of DICER1 in the 22 adenosarcomas. RESULTS: Only one patient exhibited a DICER1 mutation that was not a DICER1 Hotspot mutation. Among the 22 patients, all underwent total hysterectomy with bilateral salpingo-oophorectomy, and 14 out of these 22 patients received adjuvant treatment. CONCLUSION: In summary, our study of 22 Müllerian adenosarcomas focused on the clinicopathological features and the presence of DICER1 Hotspot mutations. Although our findings did not reveal any DICER1 mutations in the studied samples, this negative result provides valuable information for the field by narrowing down the genetic landscape of adenosarcomas and highlighting the need for further research into alternative molecular pathways driving this malignancy.


Assuntos
Adenossarcoma , Feminino , Humanos , Adenossarcoma/genética , Adenossarcoma/patologia , Mutação , China , Ribonuclease III/genética , RNA Helicases DEAD-box/genética
11.
Biomed Environ Sci ; 37(2): 178-186, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582980

RESUMO

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.


Assuntos
Vacina Antirrábica , Vírus da Raiva , Raiva , Animais , Camundongos , Raiva/prevenção & controle , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinação , China , Profilaxia Pós-Exposição
12.
Biomed Environ Sci ; 37(3): 294-302, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582993

RESUMO

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.


Assuntos
Encefalite Viral , Vírus , Humanos , Encefalite Viral/diagnóstico , Vírus/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase , DNA Viral
13.
Artigo em Inglês | MEDLINE | ID: mdl-38652610

RESUMO

The paper presents a new method for constructing self-supporting surfaces using arch beams that are designed to convert their thrust into supporting force, thereby eliminating shear stress and bending moments. Our method allows for the placement of the arch beams on the boundary or within a surface and partitions the surface into multiple self-supporting parts. The use of arch beams enhances stability and durability, adds aesthetic appeal, and allows for greater flexibility in the design process. We develop an iterative algorithm for designing selfsupporting surfaces with arch beams that enables the user to control the shape of the beams and surface through intuitive parameters and specify the desired location of the arch beams. We verify the physical stability of the structure using finite element analysis. Experimental results show that our method can produce visually pleasing self-supporting surfaces that satisfy the equilibrium equation with high accuracy.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(1): 153-158, 2024 Jan 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38615177

RESUMO

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.


Assuntos
Hemodinâmica , Lítio , Humanos , Anticonvulsivantes , Arritmias Cardíacas/induzido quimicamente , Sistema Nervoso Central
15.
BMC Psychiatry ; 24(1): 269, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600448

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.


Assuntos
Transtorno de Pânico , Humanos , Transtorno de Pânico/tratamento farmacológico , Transtorno de Pânico/genética , Transtorno de Pânico/diagnóstico , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Hidrocortisona/metabolismo , Escitalopram , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , RNA Mensageiro
16.
Nat Commun ; 15(1): 3254, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627395

RESUMO

The past century has witnessed a large number of reports on the Z/E isomerization of alkenes. However, the vast majority of them are still limited to the isomerization of di- and tri-substituted alkenes. The stereospecific Z/E isomerization of tetrasubstituted alkenes remains to be an underdeveloped area, thus lacking in a stereodivergent synthesis of axially chiral alkenes. Herein we report the atroposelective synthesis of tetrasubstituted alkene analogues by asymmetric allylic substitution-isomerization, followed by their Z/E isomerization via triplet energy transfer photocatalysis. In this regard, the stereodivergent synthesis of axially chiral N-vinylquinolinones is achieved efficiently. Mechanistic studies indicate that the benzylic radical generation and distribution are two key factors for preserving the enantioselectivities of axially chiral compounds.

17.
Bone Res ; 12(1): 23, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594236

RESUMO

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.


Assuntos
Células Endoteliais , Osteogênese , Ratos , Animais , Regeneração Óssea , Osso e Ossos , Membrana Celular
18.
J Cardiothorac Surg ; 19(1): 178, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581057

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a widespread cancer and gefitinib is a primary therapy for NSCLC patients. Nevertheless, the underlying mechanisms for the progression of acquired drug resistance have not been clarified. The aim of this study was to investigate the role of circular RNA (circ_0001786) in gefitinib-resistant NSCLC. METHODS: Firstly, the expression of circ_0001786, miR-34b-5p and SRSF1 were assayed using qRT-PCR. Subsequently, CCK-8 test was utilized to measure the semi-inhibitory concentration (IC50) of cellular gefitinib. Apoptosis was identified by flow cytometry. At last, dual luciferase assay was applied to prove the binding association between miR-34b-5p, circ_0001786 or SRSF1. RESULTS: Our research disclosed that circ_0001786 was heightened in gefitinib-resistant NSCLC cells and tissues. Knockdown of circ_0001786 restrained IC50 values of gefitinib, attenuated the clonogenic ability and facilitated apoptosis in HCC827-GR and PC9-GR. In addition, circ_0001786 was a molecular sponge for miR-34b-5p. Silencing miR-34b-5p rescued the inhibitory impact of circ_0001786 knockdown on IC50 and cell cloning ability. Moreover, miR-34b-5p directly targeted SRSF1. Importantly, circ_0001786 enhanced gefitinib tolerance and malignant development in NSCLC through miR-34b-5p/SRSF1 pathway. CONCLUSION: This research revealed a novel mechanism by which circ_0001786 enhanced NSCLC resistance to gefitinib by sponging miR-34b-5p and upregulating SRSF1. circ_0001786 was a potential target for improving the treatment of gefitinib-resistant NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Apoptose , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral , Fatores de Processamento de Serina-Arginina
19.
Steroids ; : 109424, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642598

RESUMO

OBJECTIVE: This study aimed to evaluate the effects of dehydroepiandrosterone (DHEA) and DHEA combined with a high-fat diet (HFD) treatment of reproductive and endocrine metabolism in rats and then identify an ideal model of polycystic ovary syndrome (PCOS). METHODS: Three-week-old female Sprague-Dawley rats were injected subcutaneously with DHEA or oil, fed with or without a HFD, for 21 days, during which body weight, feed intake, and estrous cycle monitoring were carried out. Fasting blood glucose was measured, and serum fasting insulin, testosterone, dihydrotestosterone (DHT), estradiol, progesterone, luteinizing hormone (LH), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were estimated by ELISA. Serum total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric assay. Whereas, histologic changes in rat ovaries were evaluated by H&E staining. Ovarian steroid hormone synthases and their protein levels (StAR, 3ß-HSD2, 17ß-HSD1, CYP11A1, CYP17A1, and CYP19A1) were examined by western blotting. RESULTS: Both DHEA and DHEA + HFD-treated rats loss of a regular estrous cycle; develop polycystic ovarian changes; significantly higher serum fasting insulin and testosterone levels; and increased ovarian StAR, 3ß-HSD2, and CYP11A1 protein levels. Additionally, rats in the DHEA + HFD-treated group were obese; had elevated fasting blood glucose, TG, DHT, AMH levels and LH:FSH ratios; increased ovarian 17ß-HSD1 protein levels. CONCLUSION: DHEA combined with HFD treatment is more effective at inducing PCOS than DHEA alone. The reproductive and endocrine metabolic aspects of this method are more consistent with the clinical characteristics of PCOS patients.

20.
Anal Chem ; 96(16): 6218-6227, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38598863

RESUMO

Currently reported aggregation-induced electroluminescence (AIECL) is usually based on the electrostatic integration of luminous monomers, and its application is still limited by the low ECL efficiency and poor structural stability of electrostatic integration-based AIECL emitters. Herein, host-guest recognition-mediated supramolecular AIECL was creatively developed to overcome the defects of electrostatic-integration-based AIECL. Cucurbit[8]uril (CB[8]) as the host recognized tris (2-phenylpyridine) iridium(III) [Ir(ppy)3] as the guest to form a novel supramolecular complex Ir-CB[8]. CB[8] can not only provide a large hydrophobic cavity to efficiently load Ir(ppy)3 and enrich coreactant tripropylamine but also utilize its carbonyl-laced portals to form intramolecular hydrogen bonds to stabilize the supramolecular structure, so Ir-CB[8] revealed excellent AIECL performance. The AIECL emitter Ir-CB[8] coupled the efficient DNA walker to construct a sensing system for miRNA-16 detection. Au nanoparticles@norepinephrine (AuNPs@NE) trapped by single-strand S1 was developed to significantly quench the ECL emission of Ir-CB[8]. When the target microRNA-16 (miRNA-16) existed, H1 was opened and the sequential assembly from H2 to H7 was triggered, forming "windmill"-like DNA walker with six Pb2+-dependent leg DNA. The assembled DNA walker, which was centered on DNA structure, had high efficiency and biocompatibility and can cut S1 to keep the DNA fragment-carrying quencher AuNPs@NE away from the electrode surface, thus restoring the ECL emission of Ir-CB[8] and realizing ultrasensitive detection of miRNA-16. Supramolecular AIECL mediated by host-guest recognition provides a new way for constructing AIECL emitters with excellent structural stability and AIECL efficiency, and an Ir-CB[8] coupling "windmill"-like DNA walker builds a promising ECL-sensing system for bioassay.

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