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1.
Chem Biodivers ; : e202400348, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616166

RESUMO

The immobilization of proteins on the surface of carriers is challenging due to the loss of protein structure and function in this process. Here, we report the development of the protein immobilization on the surface of the metallated-porphyrin complex in the porphysome nanocarrier. The conjugated Ni-porphyrin to fatty acid (as a tail) has been synthesized and independently placed at the depth of the bilayer center of Dipalmitoylphosphatidylcholine (DPPC) in which the Ni-porphyrin was at the polar region of the membrane and is thus superficial. This porphysome (DPPC: Ni-porphyrin, 4 : 1 mole ratio) was formed by supramolecular self-assembly with a diameter of 173±7 nm and zeta potential -8.5±3.4 mv, which exhibited no significant toxicity at the experimental concentrations and acceptable cellular uptake on MCF-7 cells. The physicochemical properties and specific protein binding sites of the firefly luciferase as a model protein into the porphysome (1 : 2 mole ratio) show the conjugation efficiency about 80 % and the conformation of protein was completely maintained. Furthermore, bioluminescence assay and SDS-PAGE confirmed the preservation of protein function. The stabilized platform of porphyrin-lipid structure can potentially improve the efficacy of protein functionality for a particular display, shifting porphysomes from a simple carrier to a therapeutic agent.

2.
Curr Mol Med ; 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37489777

RESUMO

BACKGROUND: Several signaling pathways are involved in the process of angiogenesis, which is one of the most important hallmarks of glioblastoma multiforme (GBM). Identifying related gene variants can help researchers work out what causes anti-angiogenesis drug resistance. OBJECTIVE: The goal of this systematic analysis was to identify all mutations and polymorphisms involved in angiogenesis pathways in GBM and their impact on clinical outcomes. METHODS: The keywords include glioblastoma, angiogenesis, signaling pathway, mutation, polymorphism, and related terms used to search ISI, PubMed, and Scopus for relevant articles published up to January 2022. The PRISMA protocol was used to conduct our systematic review. The related articles were taken into consideration. The risk of bias in the associated articles was surveyed, as well as the article scoring. Two authors collaborated on data extraction. RESULTS: The inclusion criteria were included in 32 articles out of a total of 787 articles. VEGF, HIF1a, EGFR, PI3K, and MAPK are the pathways that have been studied the most. IDH1, VEGF, VEGFR, EGFR, and HIF1a are the genes with the highest frequency of mutations or polymorphisms. CONCLUSION: In conclusion, this study found that angiogenesis in primary or recurrent GBM is linked to gene changes in eleven signaling pathways. However, some of these gene mutations have been researched numerous times in relation to angiogenesis, while others have only been studied once. Understanding these changes will help us employ combination therapies more effectively for GBM patients' survival and personal medicine.

3.
Nutr Metab Cardiovasc Dis ; 33(10): 1821-1835, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37500345

RESUMO

AIMS: Cinnamon is a polyphenol-rich spice that has beneficial effects on markers of cardio metabolic health such as lipid profile, oxidative stress, and inflammation. Despite the accumulating evidence from meta-analyses on the effects of cinnamon on these markers, their findings are controversial. Thus, this umbrella meta-analysis was performed to evaluate the present evidence and provide a conclusive clarification. DATA SYNTHESIS: We searched the following international databases from inception to January 2022: PubMed, Scopus, Web of Science and Embase, and Google Scholar. Our findings of eleven meta-analyses showed that cinnamon consumption can significantly improve total cholesterol (TC) (WMD = -1.01 mg/dL; 95% CI: -2.02, -0.00, p = 0.049), low-density lipoprotein-cholesterol (LDL-C) (WMD = -0.82 mg/dL; 95% CI: -1.57, -0.07, p = 0.032), and high-density lipoprotein-cholesterol (HDL-C) (WMD = 0.47 mg/dL; 95% CI: 0.17, 0.77, p = 0.002) levels but not triglyceride (TG) levels (WMD = -0.13 mg/dL; 95% CI: -0.58, 0.32, p = 0.570). Our results did not show any significant effect of cinnamon on malondialdehyde (MDA) levels (WMD = -0.47; 95% CI: -0.99, 0.05, p = 0.078) and C-reactive protein (CRP) levels (WMD = -1.33; 95% CI: -2.66, 0.00, p = 0.051) but there was enhanced total antioxidant capacity (TAC) in patients with type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS) (WMD = 0.34; 95% CI: 0.04, 0.64, p = 0.026) and increased levels of interleukin-6 (WMD = -1.48; 95% CI: -2.96, -0.01, p = 0.049). CONCLUSIONS: Our results support the usefulness of cinnamon intake in modulating an imbalanced lipid profile in some metabolic disorders, particularly PCOS, as well as in improving TAC and interleukin-6. The review protocol was registered on PROSPERO as CRD42022358827.


Assuntos
Diabetes Mellitus Tipo 2 , Lipídeos , Adulto , Feminino , Humanos , Antioxidantes/farmacologia , Biomarcadores , Colesterol , Cinnamomum zeylanicum , Suplementos Nutricionais , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Interleucina-6 , Estresse Oxidativo , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Pharmacol Exp Ther ; 387(1): 66-77, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37442619

RESUMO

Glioblastoma is the most common and deadly primary brain tumor in adults. All glioblastoma patients receiving standard-of-care surgery-radiotherapy-chemotherapy (i.e., temozolomide (TMZ)) recur, with an average survival time of only 15 months. New approaches to the treatment of glioblastoma, including immune checkpoint blockade and oncolytic viruses, offer the possibility of improving glioblastoma outcomes and have as such been under intense study. Unfortunately, these treatment modalities have thus far failed to achieve approval. Recently, in an attempt to bolster efficacy and improve patient outcomes, regimens combining chemotherapy and immune checkpoint inhibitors have been tested in trials. Unfortunately, these efforts have not resulted in significant increases to patient survival. To better understand the various factors impacting treatment outcomes of combined TMZ and immune checkpoint blockade, we developed a systems-level, computational model that describes the interplay between glioblastoma, immune, and stromal cells with this combination treatment. Initializing our model to spatial resection patient samples labeled using imaging mass cytometry, our model's predictions show how the localization of glioblastoma cells, influence therapeutic success. We further validated these predictions in samples of brain metastases from patients given they generally respond better to checkpoint blockade compared with primary glioblastoma. Ultimately, our model provides novel insights into the mechanisms of therapeutic success of immune checkpoint inhibitors in brain tumors and delineates strategies to translate combination immunotherapy regimens more effectively into the clinic. SIGNIFICANCE STATEMENT: Extending survival times for glioblastoma patients remains a critical challenge. Although immunotherapies in combination with chemotherapy hold promise, clinical trials have not shown much success. Here, systems models calibrated to and validated against patient samples can improve preclinical and clinical studies by shedding light on the factors distinguishing responses/failures. By initializing our model with imaging mass cytometry visualization of patient samples, we elucidate how factors such as localization of glioblastoma cells and CD8+ T cell infiltration impact treatment outcomes.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Imunoterapia/métodos , Análise de Sistemas
5.
Curr Mol Med ; 23(7): 589-605, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37282586

RESUMO

As a transcriptional regulation element, the microRNA plays a crucial role in many aspects of molecular biological processes, like cellular metabolism, cell division, cell death, cell movement, intracellular signaling, and immunity. Previous studies suggested that microRNA-214 (miR-214) is probably a valuable cancer marker. In this study, a brief updated overview of the vital dual role of miR-214 in cancer as a tumor suppressor or oncogene was provided. We also examined target genes and signaling pathways related to the dysregulation of miR-214 reported in previous experimental research on various human diseases. To highlight the critical function of miR-214 in the prognostic, diagnostic, and pathogenesis of cancer diseases, we focused on the probable clinical biomarker and drug resistance function of miR-214. The current research provides a comprehensive perspective of the regulatory mechanisms governed by miR-214 in human disease pathogenesis and a list of probable candidates for future study.


Assuntos
MicroRNAs , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Genes Supressores de Tumor , Transdução de Sinais/genética , Regulação Neoplásica da Expressão Gênica
6.
Nat Cancer ; 4(5): 665-681, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37081259

RESUMO

Glioblastomas are aggressive primary brain tumors with an inherent resistance to T cell-centric immunotherapy due to their low mutational burden and immunosuppressive tumor microenvironment. Here we report that fractionated radiotherapy of preclinical glioblastoma models induce a tenfold increase in T cell content. Orthogonally, spatial imaging mass cytometry shows T cell enrichment in human recurrent tumors compared with matched primary glioblastoma. In glioblastoma-bearing mice, α-PD-1 treatment applied at the peak of T cell infiltration post-radiotherapy results in a modest survival benefit compared with concurrent α-PD-1 administration. Following α-PD-1 therapy, CD103+ regulatory T cells (Tregs) with upregulated lipid metabolism accumulate in the tumor microenvironment, and restrain immune checkpoint blockade response by repressing CD8+ T cell activation. Treg targeting elicits tertiary lymphoid structure formation, enhances CD4+ and CD8+ T cell frequency and function and unleashes radio-immunotherapeutic efficacy. These results support the rational design of therapeutic regimens limiting the induction of immunosuppressive feedback pathways in the context of T cell immunotherapy in glioblastoma.


Assuntos
Glioblastoma , Camundongos , Humanos , Animais , Glioblastoma/radioterapia , Linfócitos T Reguladores/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/uso terapêutico , Recidiva Local de Neoplasia/metabolismo , Linfócitos T CD8-Positivos , Imunoterapia/métodos , Microambiente Tumoral
7.
J Immunother Cancer ; 11(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36725085

RESUMO

BACKGROUND: Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI. METHODS: Here, in this study, we applied imaging mass cytometry to characterize the tumor and immunological landscape of immunotherapy response in non-small cell lung cancer by describing activated cell states, cellular interactions and neighborhoods associated with improved efficacy. We functionally validated our findings using preclinical mouse models of cancer treated with anti-programmed cell death protein-1 (PD-1) immune checkpoint blockade. RESULTS: We resolved 114,524 single cells in 27 patients treated with ICI, enabling spatial resolution of immune lineages and activation states with distinct clinical outcomes. We demonstrated that CXCL13 expression is associated with ICI efficacy in patients, and that recombinant CXCL13 potentiates anti-PD-1 response in vivo in association with increased antigen experienced T cell subsets and reduced CCR2+ monocytes. DISCUSSION: Our results provide a high-resolution molecular resource and illustrate the importance of major immune lineages as well as their functional substates in understanding the role of the tumor immune microenvironment in response to ICIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiocina CXCL13 , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Microambiente Tumoral , Humanos
8.
Nature ; 614(7948): 548-554, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36725934

RESUMO

Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution1-9. Most clinical strategies rely on histopathological stratification of tumour subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm2 tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Análise de Célula Única , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Microambiente Tumoral/imunologia , Progressão da Doença , Aprendizado Profundo , Prognóstico
9.
Nature ; 614(7948): 555-563, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36725935

RESUMO

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.


Assuntos
Neoplasias Encefálicas , Glioma , Análise de Célula Única , Microambiente Tumoral , Humanos , Encéfalo/imunologia , Encéfalo/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Glioblastoma/imunologia , Glioblastoma/patologia , Glioma/imunologia , Glioma/patologia , Macrófagos/enzimologia , Microambiente Tumoral/imunologia , Metástase Neoplásica , Conjuntos de Dados como Assunto
10.
Nanomedicine ; 47: 102609, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228994

RESUMO

Drug development for multiple sclerosis (MS) clinical management focuses on both neuroprotection and repair strategies, and is challenging due to low permeability of the blood-brain barrier, off-target distribution, and the need for high doses of drugs. The changes in the extracellular matrix have been documented in MS patients. It has been shown that the expression of nidogen-1 increases in MS lesions. Laminin forms a stable complex with nidogen-1 through a heptapeptide which was selected to target the lesion area in this study. Here we showed that the peptide binding was specific to the injured area following lysophosphatidylcholine (LPC) induced demyelination. In vivo data showed enhanced delivery of the peptide-functionalized gold nanoparticles (Pep-GNPs) to the lesion area. In addition, Pep-GNPs administration significantly enhanced myelin content and reduced astrocyte/microglia activation. Results demonstrated the possibility of using this peptide to target and treat lesions in patients suffering from MS.


Assuntos
Ouro , Nanopartículas Metálicas , Humanos , Bainha de Mielina , Peptídeos/farmacologia
11.
Biosensors (Basel) ; 12(11)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36354427

RESUMO

A bioluminescence-based assay for ATP can measure cell viability. Higher ATP concentration indicates a higher number of living cells. Thus, it is necessary to design an ATP sensor that is low-cost and easy to use. Gold nanoparticles provide excellent biocompatibility for enzyme immobilization. We investigated the effect of luciferase proximity with citrate-coated gold, silver, and gold-silver core-shell nanoparticles, gold nanorods, and BSA-Au nanoclusters. The effect of metal nanoparticles on the activity of luciferases was recorded by the luminescence assay, which was 3-5 times higher than free enzyme. The results showed that the signal stability in presence of nanoparticles improved and was reliable up to 6 h for analytes measurements. It has been suggested that energy is mutually transferred from luciferase bioluminescence spectra to metal nanoparticle surface plasmons. In addition, we herein report the 27-base DNA aptamer for adenosine-5'-triphosphate (ATP) as a suitable probe for the ATP biosensor based on firefly luciferase activity and AuNPs. Due to ATP application in the firefly luciferase reaction, the increase in luciferase activity and improved detection limits may indicate more stability or accessibility of ATP in the presence of nanoparticles. The bioluminescence intensity increased with the ATP concentration up to 600 µM with a detection limit of 5 µM for ATP.


Assuntos
Ouro , Nanopartículas Metálicas , Prata , Luciferases de Vaga-Lume/genética , Luciferases de Vaga-Lume/metabolismo , Trifosfato de Adenosina , Luciferases
12.
Curr Med Chem ; 29(33): 5462-5473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35430970

RESUMO

BACKGROUND: To date, many investigations have employed pro-/synbiotic to examine their effects on chemotherapy-related side effects; nevertheless, their findings are inconclusive. To address this issue, we carried out a systematic review to explore the effect of pro- /synbiotic consumption on chemotherapy-related side effects, including nausea, vomiting, mucositis, diarrhea, and constipation in adults using randomized controlled trials (RCTs). METHODS: The electronic databases, including PubMed, Scopus, and ISI Web of Sciences, were searched systematically from the earliest available date to March 2021 to identify eligible studies. The quality of the enrolled studies was assessed based on the Cochrane Collaboration Risk of Bias tool. RESULTS: A total of 10 studies involving 788 individuals were included in the current systematic review, with the sample size ranging from 25 to 200 and the mean age ranging from 51.04 to 66.91 years. The findings of this study imply that probiotic consumption may be more effective in terms of mucositis compared to other complications. CONCLUSION: Further good-quality RCTs with better methodology are required to determine whether and how pro-/synbiotics can prevent or treat chemotherapy-induced side effects. The current systematic review findings may help investigators of future studies in selecting the study population and probiotic strains.


Assuntos
Mucosite , Probióticos , Simbióticos , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Probióticos/uso terapêutico
13.
BMC Womens Health ; 21(1): 417, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34915873

RESUMO

BACKGROUND: Diagnosis and treatment of breast cancer potentially leads to sexual dysfunction and sexual distress in women and negatively affects their quality of life (QoL). This study aimed at determining the effect of PLISSIT based counseling on sexual function, sexual distress, and QoL in women surviving breast cancer. METHODS: In this pre-test, post-test, single-group semi-experimental study, 65 women surviving breast cancer who were referred to the selected centers were included in the study via the available sampling method. Data gathering tools included a researcher-made demographic questionnaire, female sexual function index, beck depression inventory-II, State-Trait Anxiety Inventory, World Health Organization QoL-Brief, and Female Sexual Distress Scale-Revised. The counseling program (7 sessions 60 min each) was designed based on the PLISSIT model. The sexual function, sexual distress, and QoL were evaluated before, and 2 and 4 weeks after the intervention. To compare the mean scores of variables before and after the intervention, repeated-measured ANOVA was used. RESULTS: The findings showed that PLISSIT based counseling significantly reduced sexual distress and increased the scores of QoL and all its domains, as well as sexual function and all its domains in women surviving breast cancer (p < 0.05). There was no significant difference in the mean scores of variables 2 and 4 weeks after the intervention. CONCLUSIONS: It seems that PLISSIT based counseling reduces sexual dysfunction and sexual distress and improves the QoL of women surviving breast cancer. So, it is recommended that these counseling programs be integrated into the health care program of this group of women. TRIAL REGISTRATION: TCTR202103170010, 17 March 2021, Retrospectively registered, at https://www.thaiclinicaltrials.org/ .


Assuntos
Neoplasias da Mama , Disfunções Sexuais Fisiológicas , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Aconselhamento , Feminino , Humanos , Qualidade de Vida , Comportamento Sexual , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/psicologia
14.
Reprod Sci ; 28(11): 3032-3050, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34472034

RESUMO

A body of studies has examined the circulating concentration of adipokines including apelin, vapin, resistin, and chemerin in polycystic ovary syndrome (PCOS) patients. However, their findings have been inconclusive. Therefore, we systematically reviewed available studies to illuminate the overall circulating concentration of adipokines in PCOS subjects. Cochrane's Library, PubMed, Scopus, and ISI Web of Science databases were searched from the earliest available date up to April 2021 for relevant articles. The quality of each study was assessed by the Newcastle-Ottawa Quality Assessment Scale. The pooled effect size was estimated based on the random effects model, and the standard mean differences (SMD) with a 95% confidence interval (CI) were reported. A total of 88 studies met the inclusion criteria and were included in the current systematic review and meta-analysis. The results of the analysis showed that serum levels of vaspin (SMD 0.69; 95% CI, 0.22 to 1.17; P = 0.004; I2 = 90.6%), chemerin (SMD 1.87; 95% CI, 1.35 to 2.40; P < 0.001; I2 = 94.4%), and resistin (SMD 0.66; 95% CI, 0.41 to 0.91; P < 0.001; I2 = 92.6%) were significantly higher in the PCOS group compared to controls. However, there was no significant difference between the PCOS and control groups in relation to apelin levels (SMD - 0.17; 95% CI, - 1.06 to 0.73; P = 0.714; I2 = 97.8%). We found that serum levels of vaspin, chemerin, and resistin were significantly higher in PCOS subjects compared with controls. It seems that these adipokines can be measured as a useful marker to predict the development of PCOS.


Assuntos
Adipocinas/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Síndrome do Ovário Policístico/epidemiologia
15.
BMC Pregnancy Childbirth ; 21(1): 297, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845792

RESUMO

BACKGROUND: The quality of prenatal care is critical for the prevention of adverse pregnancy outcomes. However, according to the World Health Organization (WHO), only 64 % of women worldwide have access to over four sessions of prenatal care throughout their pregnancy. Thus, studies that address factors affecting maternal and child health status before and after pregnancy are of immense importance. The primary aim of the mothers and their children's health (MATCH) cohort study is to evaluate the effect of nutrition, sleep quality, and lifestyle on maternal and neonatal outcomes. METHODS: A prospective cohort of > 2500 pregnant women in the first trimester (before 12 weeks' gestation) will be recruited at Arash Women's Hospital in Tehran, Iran between February 2020 and August 2021. All eligible pregnant women will be followed from their first trimester of pregnancy until delivery at four time points and assessed through a series of in-person visits with interviewer-administered questionnaires and telephone interviews. Detailed data will be collected on maternal demographics, lifestyle, medical history, reproductive history, obstetric history, dietary intake, sleep pattern, blood specimens, and anthropometric measurements, alongside paternal demographics, lifestyle, and family history. The outcomes will include antenatal, peripartum, and postnatal maternal complications and infant growth and neurodevelopment. DISCUSSION: The results of the MATCH cohort study will support the development of contextual interventions that can enhance antenatal, peripartum, and postnatal status, neonatal outcomes, and longevity mother and child.


Assuntos
Saúde do Lactente , Estilo de Vida , Saúde Materna , Fenômenos Fisiológicos da Nutrição Materna , Sono/fisiologia , Adulto , Feminino , Seguimentos , Humanos , Recém-Nascido , Estudos Longitudinais , Estudos Observacionais como Assunto , Gravidez , Resultado da Gravidez , Cuidado Pré-Natal/organização & administração , Estudos Prospectivos
16.
Clin Nutr ; 40(5): 3182-3190, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33581951

RESUMO

BACKGROUND & AIMS: The phase angle (PA), expressed via bioelectrical impedance, is an indicator of cell membrane health and integrity, hydration, and nutritional status, and may have further application as a prognostic marker in cancer survival. However, the associations between PA and cancer survival are inconsistent and unclear. The present systematic review and meta-analysis investigated the relationship between PA and survival among adult patients diagnosed with cancer. METHODS: A systematic search of observational studies up to November 2020 was conducted through PubMed, Scopus, and ISI Web of Science. The critical appraisal of the eligible studies was performed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were performed using STATA 11.2 software. A P-value <0.05 was considered statistically significant. RESULTS: A total of 14 studies covering 2625 participants were included in this study. There was a positive and significant correlation between PA and cancer survival (Fisher's Z: 0.30; 95% CI, 0.21-0.40; P < 0.001; I2 = 0.0%). Also, there was a significant prognostic role for PA on patients' survival (HR 0.77; 95% CI, 0.74-0.81; P < 0.001; I2 = 0.0%). In other words, patients with low values of PA were 23% less likely to survive than patients with high values of PA. CONCLUSIONS: Given that predicting survival in advanced cancer patients remains a challenge, the findings of this systematic review and meta-analysis suggest that phase angle may be an important prognostic factor of survival in this population.


Assuntos
Composição Corporal , Impedância Elétrica , Neoplasias/mortalidade , Estado Nutricional , Humanos , Estudos Observacionais como Assunto , Prognóstico , Análise de Sobrevida
17.
Nat Cancer ; 2(5): 545-562, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-35122017

RESUMO

Metastasis is the leading cause of cancer-related deaths, and obesity is associated with increased breast cancer (BC) metastasis. Preclinical studies have shown that obese adipose tissue induces lung neutrophilia associated with enhanced BC metastasis to this site. Here we show that obesity leads to neutrophil-dependent impairment of vascular integrity through loss of endothelial adhesions, enabling cancer cell extravasation into the lung. Mechanistically, neutrophil-produced reactive oxygen species in obese mice increase neutrophil extracellular DNA traps (NETs) and weaken endothelial junctions, facilitating the influx of tumor cells from the peripheral circulation. In vivo treatment with catalase, NET inhibitors or genetic deletion of Nos2 reversed this effect in preclinical models of obesity. Imaging mass cytometry of lung metastasis samples from patients with cancer revealed an enrichment in neutrophils with low catalase levels correlating with elevated body mass index. Our data provide insights into potentially targetable mechanisms that underlie the progression of BC in the obese population.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Animais , Neoplasias da Mama/metabolismo , Catalase/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Neutrófilos/metabolismo , Obesidade/complicações , Estresse Oxidativo
18.
J Cell Physiol ; 236(2): 771-790, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32697389

RESUMO

CircRNAs are a superabundant and highly conserved group of noncoding RNAs (ncRNAs) that are characterized by their high stability and integrity compared with linear forms of ncRNAs. Recently, their critical role in gene expression regulation has been shown; thus, it is not far-fetched to believe that their abnormal expression can be a cause of different kinds of diseases such as cancer, neurodegenerative, and autoimmune diseases. They can have a function in variety of biological processes such as microRNA (miRNA) sponging, interacting with RNA-binding proteins, or even an ability to translate to proteins. A huge challenge in finding diagnostic biomarkers is finding noninvasive biomarkers that can be detected in human fluids, especially blood samples. CircRNAs are becoming candidate biomarkers for diagnosis and prognosis of these diseases through their ability to transverse from the blood-brain barrier and their broad presence in circulating exosomes. The circRNA for miRNA-7 (ciRS-7) is newly recognized, and acknowledged to being related to human pathology and cancer progression. In this review, we first briefly summarize the latest studies about their characteristics, biogenesis, and their mechanisms of action in the regulation and development of human diseases. Finally, we provide a list of diseases that are linked to one member of this novel class of ncRNAs called ciRS-7.


Assuntos
Neoplasias/genética , RNA Longo não Codificante/genética , Animais , Biomarcadores Tumorais/genética , Exossomos/genética , Humanos , Neoplasias/patologia , Prognóstico
19.
Arch Bone Jt Surg ; 8(3): 400-406, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32766399

RESUMO

BACKGROUND: Acquiring knowledge about anatomic and geometric quantities of bones is among the most vital parameters in orthopedic surgery that has a significant effect on the treatment of various disorders and subsequent outcomes. The aim of this study was to obtain anthropometric information for distal femur in order to compare with similar dimensions of prosthesis used in total knee arthroplasty (TKA) surgery and to design more suitable and optimal components. METHODS: Morphological data of distal femur were measured in 132 knees (81 males and 51 females) using magnetic resonance imaging (MRI). The data included anterior-posterior (AP) length, medial-lateral (ML) width, medial AP (MAP), lateral AP (LAP), MAP to LAP distance in the anterior distal femur namely anterior medial lateral (AML) width, medial and lateral condyle width, and intercondylar notch. The aspect ratio (ML/AP) was also calculated and the results were compared with similar dimensions of currently used knee implants. RESULTS: Our data showed that men are significantly larger in all dimensions than women. In the distal femur with similar AP lengths in both sexes, women had a smaller ML width than men (P<0.001). Comparison between the distal femur and studied prostheses showed no high correlation and similarity between the femoral component and femoral condyle prostheses in the resected surface of the bone. CONCLUSION: The results of this study can provide the data needed to design prostheses suitable for the Iranian population.

20.
Lipids Health Dis ; 19(1): 60, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32248805

RESUMO

BACKGROUND: Different therapies have been suggested for polycystic ovary syndrome (PCOS), but changes in lifestyle and diet have been considered. Diet and dietary factors can be very effective in modifying the disease. The positive effects of probiotic and synbiotics supplementation on improving lipid profiles and anthropometric indices have been examined in various diseases. This study was conducted to evaluate the effects of synbiotics supplementation on lipid and anthropometric profiles in infertile women with PCOS. METHODS: PCOS patients aged 19-37 years old were randomized to receive either synbiotics supplement (n = 50) or placebo (n = 49) for 12 weeks. RESULTS: Consumption of synbiotics compared to the placebo, resulted in a significant decrease in Low-density lipoprotein cholesterol (LDL) value (Change Mean Difference (CMD): 4.66, 95%CI: 0.20, 9.13) and a significant increase in high-density lipoprotein cholesterol (HDL) (CMD: 1.80, 95%CI: 0.34, 3.26). Although we failed to find a significant effect of synbiotics consumption on total cholesterol (TC) and triglyceride (TG) levels. We did not find differences in anthropometric indices between groups. CONCLUSIONS: Overall, 12 weeks of synbiotics supplementation among PCOS women resulted in beneficial effects on LDL and HDL, although it is not yet clear how much our findings are clinically significant and more clinical studies with larger sample sizes are still needed. TRIAL REGISTRATION: Iranian Registry of clinical Trial, IRCT.ir, ID: IRCT2014110515536N2. Registered on 19 December 2015.


Assuntos
Síndrome do Ovário Policístico/tratamento farmacológico , Simbióticos , Adulto , Antropometria , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Triglicerídeos/sangue , Adulto Jovem
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