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1.
PLoS One ; 19(4): e0298775, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662757

RESUMO

BACKGROUND: Activated neutrophils release depolymerized chromatin and protein particles into the extracellular space, forming reticular Neutrophil Extracellular Traps (NETs). This process is accompanied by programmed inflammatory cell death of neutrophils, known as NETosis. Previous reports have demonstrated that NETosis plays a significant role in immune resistance and microenvironmental regulation in cancer. This study sought to characterize the function and molecular mechanism of NETosis-correlated long non-coding RNAs (NCLs) in the prognostic treatment of liver hepatocellular carcinoma (LIHC). METHODS: We obtained the transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and evaluated the expression of NCLs in LIHC. A prognostic signature of NCLs was constructed using Cox and Last Absolute Shrinkage and Selection Operator (Lasso) regression, while the accuracy of model was validated by the ROC curves and nomogram, etc. In addition, we analyzed the associations between NCLs and oncogenic mutation, immune infiltration and evasion. Finally, LIHC patients were classified into four subgroups based on consensus cluster analysis, and drug sensitivity was predicted. RESULTS: After screening, we established a risk model combining 5 hub-NCLs and demonstrated its reliability. Independence checks suggest that the model may serve as an independent predictor of LIHC prognosis. Enrichment analysis revealed a concentration of immune-related pathways in the high-risk group. Immune infiltration indicates that immunotherapy could be more effective in the low-risk group. Upon consistent cluster analysis, cluster subgroup 4 presented a better prognosis. Sensitivity tests showed the distinctions in therapeutic effectiveness among various drugs in different subgroups. CONCLUSION: Overall, we have developed a prognostic signature that can discriminate different LIHC subgroups through the 5 selected NCLs, with the objective of providing LIHC patients a more precise, personalized treatment regimen.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Humanos , Prognóstico , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/imunologia , Masculino , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Neutrófilos/imunologia , Feminino , Transcriptoma , Nomogramas , Biomarcadores Tumorais/genética
2.
Commun Biol ; 7(1): 394, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561421

RESUMO

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.


Assuntos
Diagnóstico por Imagem , Técnicas Genéticas , Animais , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Corantes , Mamíferos/genética
3.
J Ethnopharmacol ; 331: 118237, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38688355

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored. AIM OF THE STUDY: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage. MATERIALS AND METHODS: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H2O2-induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit. RESULTS: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H2O2-induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway. CONCLUSION: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway.


Assuntos
Disfunção Cognitiva , Medicamentos de Ervas Chinesas , Mitocôndrias , Estresse Oxidativo , Ratos Sprague-Dawley , Sirtuína 3 , Superóxido Dismutase , Animais , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Células PC12 , Masculino , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Fármacos Neuroprotetores/farmacologia , Sirtuínas
4.
Curr Med Sci ; 43(6): 1075-1083, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38041791

RESUMO

Endometrial receptivity is an important factor that influences embryo implantation. Thus, it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology. Recently, growing evidence has indicated that intrauterine platelet-rich plasma (PRP) infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity. Therefore, the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.


Assuntos
Transferência Embrionária , Plasma Rico em Plaquetas , Humanos , Feminino , Implantação do Embrião , Endométrio , Técnicas de Reprodução Assistida
5.
Sci Rep ; 13(1): 12129, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495629

RESUMO

The purpose is to analyze and compare postoperative recovery and complication incidence between a periareolar incision combined with Suspension-type Mastoscopic Axillary Lymph Node Dissection (SMALND) and traditional inflated Mastoscopic Axillary Lymph Node Dissection (MALND). This was a randomized trial conducted from June 1, 2020, to April 30, 2022, in the Department of Second Breast Surgery, Shengjing Hospital of China Medical University, and the Department of Thyroid and Breast Surgery, Zibo Central Hospital, in accordance with the criteria of inclusion and exclusion. Overall, 126 patients diagnosed and treated for early-stage breast cancer were selected to undergo periareolar-incision breast-conserving surgery. Those patients who underwent periareolar-incision surgery combined with SMALND formed the observation group (SMALND Group), while those who underwent periareolar-incision surgery combined with traditional inflation became MALND Group. In the two groups, paired data "t" was used to examine, analyze, and compare the postoperative daily drainage volume and drain removal time, while paired data "χ2" was used to examine, analyze, and compare the incidences of postoperative upper limb edema and paresthesia. There were 64 cases in the SMALND Group and 62 cases in the MALND Group. Between the two clusters, no differences were found in age, clinical staging, BMI, and breast cancer classification (P > 0.05). The intraoperative surgery time of the SMALND Group was 43.37 ± 6.27 min while that of the MALND Group was longer: 45.72 ± 4.25 min (P < 0.05). The intraoperative hemorrhage volume of the SMALND Group was 88.33 ± 16.79 ml, less than that of the MALND Group: 96.76 ± 26.85 ml (P < 0.05). The postoperative axillary mean daily drainage volume of the SMALND Group was 38.17 ± 5.55 ml, less than that of the MALND Group: 40.72 ± 7.25 ml (P < 0.05). The drain removal time of the SMALND Group was 7.50 ± 1.60, less than that of the MALND Group: 9.00 ± 1.80 (P < 0.05). The upper limb edema incidence rate of the SMALND Group was 3.12% (2/64) and had no obvious difference from the MALND Group, which was 4.83% (3/62) (P = 0.62). The paresthesia incidence rate of the SMALND Group was 18.75% (12/64), while that of the MALND Group was 17.7% (11/62), without an obvious difference (P = 0.88). For axillary lymph node dissection, the use of non-lipolytic suspension-type mastoscopy has reduced the intraoperative hemorrhage volume of patients, shortened surgery time and postoperative recovery time, saved treatment expenses for patients, and avoided complications such as hypercapnia and subcutaneous emphysema caused by traditional inflated mastoscopic surgery. Moreover, it has not increased the incidence of postoperative upper limb edema and paresthesia, supporting its safety and effectiveness.


Assuntos
Neoplasias da Mama , Ferida Cirúrgica , Feminino , Humanos , Axila/cirurgia , Axila/patologia , Perda Sanguínea Cirúrgica , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Edema , Estudos de Viabilidade , Excisão de Linfonodo , Mastectomia Segmentar/efeitos adversos , Parestesia , Ferida Cirúrgica/cirurgia
6.
BMJ Open ; 13(6): e073038, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37355267

RESUMO

INTRODUCTION: Myocardial injury after non-cardiac surgery (MINS) caused by an ischaemic mechanism is common and is associated with adverse short-term and long-term prognoses. However, MINS is a recent concept, and few studies have prospectively used it as a primary outcome. Remote ischaemic preconditioning (RIPC) is a non-invasive procedure that induces innate cardioprotection and may reduce MINS. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled, observer-blinded trial. Patients with a high clinical risk of cardiovascular events who are scheduled to undergo major abdominal surgery will be enrolled. A total of 766 participants will be randomised (1:1 ratio) to receive RIPC or control treatment before anaesthesia. RIPC will comprise four cycles of cuff inflation for 5 min to 200 mm Hg and deflation for 5 min. In the controls, an identical-looking cuff will be placed around the arm but will not be actually inflated. The primary outcome will be MINS, defined as at least one postoperative cardiac troponin (cTn) concentration above the 99th percentile upper reference limit of the cTn assay as a result of a presumed ischaemic mechanism. This trial will test the concentration of high-sensitivity cardiac troponin T (hs-cTnT). The secondary outcomes will be hs-cTnT levels reaching/above the prognostically important thresholds, peak hs-cTnT and total hs-cTnT release during the initial 3 days after surgery, length of hospital stay after surgery, length of stay in the intensive care unit, myocardial infarction, major adverse cardiovascular events, cardiac-related death, all-cause death within 30 days, 6 months, 1 year and 2 years after surgery, and postoperative complications and adverse events within 30 days after surgery. ETHICS AND DISSEMINATION: This study protocol (version 5.0 on 7 April 2023) was approved by the Ethics Committee of Sixth Affiliated Hospital of Sun Yat-sen University. The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05733208.


Assuntos
Precondicionamento Isquêmico Miocárdico , Precondicionamento Isquêmico , Infarto do Miocárdio , Humanos , Resultado do Tratamento , Precondicionamento Isquêmico/efeitos adversos , Precondicionamento Isquêmico/métodos , Infarto do Miocárdio/etiologia , Prognóstico , Projetos de Pesquisa , Precondicionamento Isquêmico Miocárdico/efeitos adversos , Precondicionamento Isquêmico Miocárdico/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
7.
Cell Div ; 18(1): 7, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194024

RESUMO

BACKGROUND: circular RNAs (circRNAs) have been considered novel biomarker candidates for human cancers, such as triple-negative breast cancer (TNBC). circ_0001006 was identified as a differentially expressed circRNA in metastatic breast cancer, but its significance and function in TNBC were unclear. The significance of circ_0001006 in TNBC was assessed and exploring its potential molecular mechanism to provide a therapeutic target for TNBC. RESULTS: circ_0001006 showed significant upregulation in TNBC and close association with patients' histological grade, Ki67 level, and TNM stage. Upregulated circ_0001006 could predict a worse prognosis and high risk of TNBC patients. In TNBC cells, silencing circ_0001006 suppressed cell proliferation, migration, and invasion. In mechanism, circ_0001006 could negatively regulate miR-424-5p, which mediated the inhibition of cellular processes by circ_0001006 knockdown. CONCLUSIONS: Upregulated circ_0001006 in TNBC served as a poor prognosis predictor and tumor promoter via negatively regulating miR-424-5p.

8.
Tohoku J Exp Med ; 261(1): 25-33, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37164696

RESUMO

Resistance to docetaxel is a major problem to the success of docetaxel-based therapies for breast cancer. The present study was to identify the role of circABCB1 in altering the docetaxel resistance properties. Reverse transcription-quantitative PCR (qRT-PCR) was performed to quantify circABCB1 and miR-153-3p. The effects of circABCB1 on the viability, apoptosis and migration/invasion of docetaxel-resistant and -sensitive cells were investigated by cell function experiments, including Cell Counting Kit-8 and Transwell assays. Correlation between circABCB1 and the docetaxel-treated outcome was analyzed by multivariate Cox regression analysis, in addition to Kaplan-Meier analysis of time to treatment failure (TTF). The targeting relationship between circABCB1 and miR-153-3p was predicted and verified by dual-luciferase reporter assay and RNA immunoprecipitation. CircABCB1 was highly expressed in cancerous tissues, as well as the docetaxel-sensitive group and cells. The overexpression of circABCB1 contributed to cell viability, docetaxel-resistance and migration/invasion, but inhibited apoptosis. CircABCB1 can sponge miR-153-3p. CircABCB1 contributed to the docetaxel resistance of breast cancer, maybe via the miR-153-3p.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Docetaxel/farmacologia , RNA Circular/genética , RNA Circular/farmacologia , MicroRNAs/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Apoptose/genética , Proliferação de Células
9.
J Microbiol Immunol Infect ; 56(4): 747-756, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37080838

RESUMO

BACKGROUND: More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. METHODS: HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. RESULTS: Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. CONCLUSION: Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.


Assuntos
Antineoplásicos , Neoplasias Hematológicas , Hepatite B , Neoplasias , Humanos , Vírus da Hepatite B/genética , Incidência , Estudos Retrospectivos , Antineoplásicos/efeitos adversos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Antivirais/uso terapêutico , Antivirais/farmacologia , Ativação Viral , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B
10.
Cell Signal ; 106: 110592, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36641081

RESUMO

Natural compounds that interfere with tumor cell growth have potential to be used as therapeutic agents to treat cancers. Lachnochromonin (p71) is a small molecule isolated from Lachnum virgineum. Here, we reported the effect of p71 on human tumor cells, especially on breast cancer MCF-7 cells. We found that p71 significantly suppresses cell growth and induces apoptosis. The luciferase results demonstrated that p71 specifically attenuates the activation of JAK/STAT3 signaling. Biochemical analysis revealed that p71 blocks the phosphorylation of STAT3 tyrosine 705 and serine 727, resulting in down-regulation of c-Myc and Cyclin D1 expression level. Importantly, p71 inhibited cell growth, colony-formation, and migration through affecting STAT3 activity. These results implied that p71 may be used as a therapeutic agent against breast cancer.


Assuntos
Apoptose , Neoplasias da Mama , Humanos , Feminino , Linhagem Celular Tumoral , Transdução de Sinais , Proliferação de Células , Fosforilação , Neoplasias da Mama/patologia , Fator de Transcrição STAT3/metabolismo
11.
Vet Microbiol ; 279: 109664, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36716634

RESUMO

Physcion, a natural anthraquinone derivative, has been reported to exert remarkable antibacterial activities against Staphylococcus aureus,Staphylococcus epidermidis and Pseudomonas aeruginosa. However, it is not fully illustrated as anti-Chlamydia substance. In the present study, minimum inhibitory concentration(MIC)values for physcion against Chlamydia psittaci(C.psittaci) 6BC, C.psittaci SBL and C.psittaci HJ were 128 µg/mL,256 µg/mL and 128 µg/mL while minimum bactericidal concentration (MBC) values were 256 µg/mL,512 µg/mL and 256 µg/mL,respectively. Moreover, Chlamydial adhesion to Hela 229 cells was blocked in a dose-dependent manner and RB-to-EB differentiation was inhibited by physcion from 28 to 48 hpi.Post treatment,upregulation of LC3-II was in a dose-dependent manner, indicating physcion activated autophagy and bacterial clearance.To validate clinical efficacy,49 SPF chickens aged 21days were divided into 5 groups and infected intra-laryngeally with 0.2 mL of 1 × 107 IFU/mL C.psittaci 6 BCE.Three days later, birds received orally with serial doses of physcion (4 mg/kg to 9 mg/kg), or 3 mg/kg of doxycycline for 6 days.Chickens with difficulty in breathing were alleviated significantly with increasing concentrations of physicon.Postmortem,lesions of air sacs were reduced significantly in a dose-dependent manner.More importantly,birds with 9 mg/kg of physcion could alleviate lesions of air sacs and lungs, and reduce bacterial loads in spleens, which was comparable to doxycycline treatment. Based on above evidences, physcion is a promising cost-effective natural drug by blocking Chlamydial adhesions to host cells, RB-to-EB differentiation and activating bacterial autophagy and it will be a good alternative to doxycycline combating virulent C.psittaci infection, contributing to eradication of Chlamydial transmission from animals to human beings.


Assuntos
Chlamydia , Chlamydophila psittaci , Psitacose , Humanos , Animais , Chlamydophila psittaci/fisiologia , Antraquinonas , Doxiciclina , Galinhas , Psitacose/microbiologia , Psitacose/veterinária
12.
Zhonghua Nan Ke Xue ; 29(7): 660-664, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-38619417

RESUMO

Prostate cancer (PCa) is one of the most common malignant tumors of the genitourinary system in middle-aged and elderly men. The incidence of PCa has been increasing year by year in China in recent years, posing a major threat to the physical and mental health of Chinese men. With the rapid development of nanotechnology, the research of nanomaterials in biomedicine is increasing, which effectively promotes the application of nanomaterials in the early diagnosis of a variety of tumors, including PCa. This article reviews the latest research progress of nanomaterials in the diagnosis of PCa.


Assuntos
Nanoestruturas , Neoplasias da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , China , Saúde Mental , Neoplasias da Próstata/diagnóstico , População do Leste Asiático , Nanomedicina
13.
J Interv Cardiol ; 2022: 5451947, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419957

RESUMO

Pulmonary hypertension (PH) is a type of clinical pathophysiological syndrome characterized by a progressive increase in pulmonary vascular resistance and subsequent progressive failure of the right heart function, and is a common complication of many diseases. Mesenchymal stem cells (MSCs) autonomously home to sites damaged by disease, repair damaged tissues, and participate in the regulation of systemic inflammation and immune responses, which have good clinical application prospects. Extracellular vesicles (EVs), such as exosomes and microvesicles, participate in various biological activities by regulating intercellular communication. Exosomes secreted into the extracellular environment also affect the host immune system. MSC-derived extracellular vesicles (MSC-EVs), as a mediator in the paracrine processes of MSCs, carry biologically active substances such as proteins, lipids, mRNA, and micro-RNA. MSC-EVs therapies, safer than cell-based treatments, have been shown to be effective in modulating macrophages to support anti-inflammatory phenotypes, which are strongly related to histological and functional benefits in preclinical models of pulmonary hypertension. The main effects of active substances and their potential medical value have attracted wide attention from researchers. This article reviews the role and relevant mechanisms of MSC-EVs in the treatment of pulmonary hypertension in recent studies and provides a basis for their future clinical applications.


Assuntos
Exossomos , Vesículas Extracelulares , Hipertensão Pulmonar , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Hipertensão Pulmonar/terapia , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo
14.
Lupus ; 31(14): 1706-1713, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36148853

RESUMO

BACKGROUND: Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy. METHODS: English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs). RESULTS: Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83-36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04-9.89). CONCLUSION: Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC. Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation.


Assuntos
Lúpus Eritematoso Sistêmico , Insuficiência Ovariana Primária , Gravidez , Humanos , Feminino , Hormônio Liberador de Gonadotropina , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico
15.
Front Pharmacol ; 13: 902290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694242

RESUMO

Cyclic adenosine 3',5'-monophosphate (cAMP) is an important intracellular second messenger molecule downstream of many G protein-coupled receptors (GPCRs). Fluorescence imaging with bright and sensitive cAMP indicators allows not only dissecting the spatiotemporal dynamics of intracellular cAMP, but also high-content screening of compounds against GPCRs. We previously reported the high-performance circularly permuted GFP (cpGFP)-based cAMP indicator G-Flamp1. Here, we developed improved G-Flamp1 variants G-Flamp2 and G-Flamp2b. Compared to G-Flamp1, G-Flamp2 exhibited increased baseline fluorescence (1.6-fold) and larger fluorescence change (ΔF/F0) (1,300% vs. 1,100%) in HEK293T cells, while G-Flamp2b showed increased baseline fluorescence (3.1-fold) and smaller ΔF/F0 (400% vs. 1,100%). Furthermore, live cell imaging of mitochondrial matrix-targeted G-Flamp2 confirmed cytosolic cAMP was able to enter the mitochondrial matrix. G-Flamp2 imaging also showed that adipose tissue extract activated the Gi protein-coupled orphan GPCR GPR50 in HEK293T cells. Taken together, our results showed that the high-performance of G-Flamp2 would facilitate sensitive intracellular cAMP imaging and activity measurement of compounds targeting GPCR-cAMP signaling pathway during early drug development.

16.
AAPS PharmSciTech ; 23(6): 181, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35773548

RESUMO

Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new excipients exploration are needed to improve the water-solubility and comfort of the drug administration. In the present study, novel etoposide-loaded submicron emulsions (ESE) with the biosurfactants of acidic sophorolipid (ASL) and lactonic sophorolipid (LSL) instead of the chemical surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain triglyceride: long-chain triglyceride (MCT:LCT), lecithin concentration, homogenization pressure and cycle, and type and concentration of surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher drug loading capacity, slower release rate, and significantly increased antitumor activity against ovarian cancer cell line A2780 via apoptosis than Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and Tween-ESE caused no hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the hemolysis test, making ASL more reliable for drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Emulsões/química , Etoposídeo , Excipientes , Feminino , Humanos , Ácidos Oleicos , Polissorbatos , Tensoativos/química , Triglicerídeos/química
17.
Multimed Tools Appl ; 81(11): 15671-15686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250359

RESUMO

The abnormal traits and colors of feces typically indicate that the patients are probably suffering from tumor or digestive-system diseases. Thus a fast, accurate and automatic health diagnosis system based on feces is urgently necessary for improving the examination speed and reducing the infection risk. The rarity of the pathological images would deteriorate the accuracy performance of the trained models. In order to alleviate this problem, we employ augmentation and over-sampling to expand the samples of the classes that have few samples in the training batch. In order to achieve an impressive recognition performance and leverage the latent correlation between the traits and colors of feces pathological samples, a multi-task network is developed to recognize colors and traits of the macroscopic feces images. The parameter number of a single multi-task network is generally much smaller than the total parameter number of multiple single-task networks, so the storage cost is reduced. The loss function of the multi-task network is the weighted sum of the losses of the two tasks. In this paper, the weights of the tasks are determined according to their difficulty levels that are measured by the fitted linear functions. The sufficient experiments confirm that the proposed method can yield higher accuracies, and the efficiency is also improved.

18.
J Clin Ultrasound ; 50(6): 862-868, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35338779

RESUMO

The dual-energy computed tomography (DECT) and diffusion-weighted magnetic resonance imaging (DWI-MRI) are used to diagnose liver cancer. The clinical value of these two examination methods needs to be further summarized. We collected and summarized relevant literature published from 2011 to 2021. The diagnostic performance of DECT was assessed between conventional computed tomography and DWI-MRI. DWI-MRI had a 69% sensitivity for detecting small hepatocellular carcinoma (HCC) lesions and a 60% diagnostic specificity for differentiating between types of HCC lesions. DECT had a sensitivity to small liver lesions (<1 cm) of 69%, and the diagnostic specificity for HCC and metastasis was about 60%. DWI was more sensitive (90.3% vs. 74.9%) and accurate (91.9% vs. 76.9%) in diagnosing HCC compared with conventional MRI sequencing. With the aid of contrast media, DWI-MRI had 90.0% specificity for detecting small HCCs (smaller than 1 cm). Furthermore, DWI-MRI not only provided physicians with valuable diagnostic information but also delivered histological grading information, with 78% accuracy for all benign lesions and 71% for solid lesions. DECT had relatively high sensitivity and required a lower contrast medium dose. With standardized quantitative parameters, it can be an extremely useful tool for HCC surveillance. DWI-MRI is the preferred imaging process as it produces high-contrast images for supporting an early diagnosis (high sensitivity and specificity) and provides histological information using non-ionizing radiation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Clin Breast Cancer ; 22(4): 374-380, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35216934

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer with an unsatisfied prognosis. Effective biomarkers could predict the risk and improve patients' survival. Whether LINC00466 possesses the potential to serve as a biomarker of the progression and prognosis of TNBC was evaluated. MATERIALS AND METHODS: A total of 122 TNBC patients were included in this study and provided paired clinical tissues. The expression of LINC00466 in TNBC was evaluated by RT-qPCR and evaluated the clinical significance with a series of statistical analyses. The biological effects and the mechanism were investigated in TNBC cells with CCK8, Transwell, and luciferase reporter assays. RESULTS: LINC00466 was significantly upregulated in TNBC and showed close association with the clinical features of patients, which indicates the development, and severity of patients. LINC00466 functioned as a prognostic biomarker predicting the survival of patients and a tumor promoter improving the proliferation, migration, and invasion of TNBC cells through sponging miR-539-5p. CONCLUSION: LINC00466 promotes the progression of TNBC via regulating miR-539-5p. The inhibition of LINC00466 might be a novel therapeutic strategy for TNBC.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA Longo não Codificante/genética , Neoplasias de Mama Triplo Negativas/patologia
20.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193966

RESUMO

Photoacoustic (PA) imaging offers promise for biomedical applications due to its ability to image deep within biological tissues while providing detailed molecular information; however, its detection sensitivity is limited by high background signals that arise from endogenous chromophores. Genetic reporter proteins with photoswitchable properties enable the removal of background signals through the subtraction of PA images for each light-absorbing form. Unfortunately, the application of photoswitchable chromoproteins for tumor-targeted imaging has been hampered by the lack of an effective targeted delivery scheme; that is, photoswitchable probes must be delivered in vivo with high targeting efficiency and specificity. To overcome this limitation, we have developed a tumor-targeting delivery system in which tumor-homing bacteria (Escherichia coli) are exploited as carriers to affect the point-specific delivery of genetically encoded photochromic probes to the tumor area. To improve the efficiency of the desired background suppression, we engineered a phytochrome-based reporter protein (mDrBphP-PCMm/F469W) that displays higher photoswitching contrast than those in the current state of the art. Photoacoustic computed tomography was applied to achieve good depth and resolution in the context of in vivo (mice) imaging. The present system effectively integrates a genetically encoded phytochrome-based reporter protein, PA imaging, and synthetic biology (GPS), to achieve essentially background-suppressed tumor-targeted PA monitoring in deep-seated tissues. The ability to image tumors at substantial depths may enable target-specific cancer diagnoses to be made with greater sensitivity, fidelity, and specificity.


Assuntos
Neoplasias/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Fitocromo/metabolismo , Animais , Linhagem Celular Tumoral , Escherichia coli , Feminino , Genes Reporter/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Molecular/métodos , Fitocromo/farmacologia , Análise Espectral/métodos , Tomografia Computadorizada por Raios X/métodos
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