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1.
Am J Clin Nutr ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38763424

RESUMO

BACKGROUND: Anthropometric indicators have been shown to be associated with the prognosis of patients with cancer. However, any single anthropometric index has limitation in predicting the prognosis. OBJECTIVE: This study aimed to observe the predictive role of seven anthropometric indicators based on body size on the prognosis of patients with cancer. DESIGN: A principal component analysis (PCA) on seven anthropometric measurements: height, weight, body mass index (BMI), hand grip strength (HGS), triceps skinfold thickness (TSF), mid-upper arm circumference (MAC), and calf circumference (CAC) was conducted. Principal components (PCs) were derived from this analysis. Cox regression analysis was used to investigate the association between the prognosis of patients with cancer and the PCs. Subgroups and sensitivity analyses were also conducted. RESULTS: Through PCA, four distinct PCs were identified, collectively explaining 88.3% of the variance. PC1, primarily characterized by general obesity, exhibited a significant inverse association with the risk of cancer death (adjusted HR=0.86, 95% CI (0.83, 0.88)). PC2 (short stature with high TSF) was not significantly associated with cancer prognosis. PC3 (high BMI coupled with low HGS) demonstrated a significant increase with the risk of cancer-related death (adjusted HR=1.08, 95% CI (1.05, 1.11)). PC4 (tall stature with high TSF) exhibited a significant association with increased cancer risk (adjusted HR=1.05, 95% CI (1.02, 1.07)). These associations varied across different cancer stages. The stability of the results was confirmed through sensitivity analyses. CONCLUSION: Different body sizes are associated with distinct prognostic outcomes in patients with cancer. The impact of BMI on prognosis is influenced by both HGS and subcutaneous fat. This finding may influence the clinical care of cancer and improve the survival of cancer patients.

2.
Mech Ageing Dev ; 219: 111939, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744412

RESUMO

This study aimed to develop a clinically applicable inflammaging score by combining the inflammatory status and age of patients. Kaplan-Meier analysis was used to compare survival differences among patients with different grades of inflammation scores. Cox proportional hazard regression analysis was used to explore the relationship between the inflammaging score and survival. As the age of patients increased, their levels of systemic inflammation gradually increased. A unique inverse relationship was found between the level of inflammation and cancer prognosis during the ageing process. Mediation analysis indicated that systemic inflammation mediates 10.1%-17.8% of the association between ageing and poor prognosis. With an increase in the inflammaging score from grades I to V, the survival rate showed a gradient decline. The inflammation score could effectively stratify the prognosis of patients with lung, bronchial, gastrointestinal, and other types of cancers. Compared with grade I, the hazard ratios for grades II-V were 1.239, 1.604, 1.724, and 2.348, respectively. In the external validation cohort, the inflammaging score remained an independent factor affecting the prognosis of patients with cancer. The inflammaging score, which combines ageing and inflammation, is a robust prognostic assessment tool for cancer patients.

3.
J Exp Clin Cancer Res ; 43(1): 96, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561776

RESUMO

Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.


Assuntos
Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia , Biópsia Líquida/métodos , Prognóstico , Células Neoplásicas Circulantes/metabolismo
4.
Nutr J ; 23(1): 45, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644466

RESUMO

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. METHODS: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan-Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. RESULTS: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan-Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. CONCLUSIONS: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.


Assuntos
Neoplasias da Mama , Colesterol , Lipoproteínas , Humanos , Feminino , Neoplasias da Mama/mortalidade , Colesterol/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Prognóstico , Adulto , Estimativa de Kaplan-Meier , Fatores de Risco , Modelos de Riscos Proporcionais , Biomarcadores/sangue , Triglicerídeos/sangue , Idoso
5.
J Affect Disord ; 357: 68-76, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38615842

RESUMO

BACKGROUND: Depression is a common psychological disorder worldwide, affecting mental and physical health. Previous studies have explored the benefits of polyunsaturated fatty acids (PUFAs) intake in depressive symptoms; however, few studies have focused on the association between all types of fatty acids intake and depressive symptoms. Therefore, we explored the relationship between the intake of different fatty acids intake and the risk of depressive symptoms. METHODS: The study was based on the data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a large US-based database. We used a nutrient residual model and multi-nutrient density model for the analysis. We calculated the nutrient density and residual in men and women separately, and the fatty acids intake was divided into quartiles based on the sex distribution. The relationship between the depressive symptoms and the intake of different fatty acids was examined using logistic regression; furthermore, we explored the relationships separately in men and women. RESULTS: The intake of monounsaturated fatty acids (MUFAs) and PUFAs, particularly n-3 and n-6 PUFAs, were associated with reduced odds ratios for depressive symptoms. The inverse relationship between the intake of MUFAs, PUFAs, n-3, and n-6 PUFAs and depressive symptoms was stronger in women. The inverse relationship between total fatty acid (TFAs) intake and depressive symptoms existed only in a single model. In contrast, saturated fatty acid (SFAs) intake was not related to depressive symptoms. CONCLUSION: Consuming MUFAs and PUFAs can counteract the depressive symptoms, especially in women.


Assuntos
Depressão , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Depressão/epidemiologia , Adulto , Pessoa de Meia-Idade , Ácidos Graxos/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Estados Unidos/epidemiologia , Ácidos Graxos Insaturados/administração & dosagem , Estudos Transversais , Ácidos Graxos Ômega-6/administração & dosagem , Fatores Sexuais , Adulto Jovem , Idoso
6.
Oncol Res ; 32(5): 955-963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686049

RESUMO

Background: Bortezomib results in peripheral neuropathy (PN) in approximately 50% of patients, during multiple myeloma (MM) treatment, a complication known as Bortezomib-induced peripheral neuropathy (BIPN). The drug response varies among individuals. Genetic factor may play an important role in BIPN. Methods: A next-generation sequencing (NGS) panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy. mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR (RT-qPCR). Serum homocysteine (Hcy) levels were detected in 40 samples by chemiluminescent microparticle immunoassay (CMIA). Results: Compared with the non-BIPN group (n = 89), a total of 8 significantly associated single nucleotide polymorphisms (SNPs) were identified in the BIPN group (n = 115): MTHFR (rs1801131, rs1801133, rs17421511), EPHX1 (rs1051740), MME (rs2016848), ALDH1A1 (rs6151031), HTR7 (rs1935349) and CYP2A6 (rs8192720). The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment (NP group) was lower than that of newly diagnosed patients without peripheral neuritis after treatment (NnP group) (1.70 ± 0.77 vs. 2.81 ± 0.97, p= 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 µmol/L vs. 8.52 ± 3.29 µmol/L, p= 0.016) and healthy controls (11.66 ± 1.79 µmol/L vs. 8.55 ± 2.13 µmol/L, p≤ 0.001). Conclusion: CYP2A6, EPHX1, MTHFR, ALDH1A1, HTR7, MME and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower MTHFR mRNA expression, which might result in higher serum Hcy levels.


Assuntos
Bortezomib , Metilenotetra-Hidrofolato Redutase (NADPH2) , Mieloma Múltiplo , Doenças do Sistema Nervoso Periférico , Polimorfismo de Nucleotídeo Único , Humanos , Bortezomib/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Masculino , Feminino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Idoso , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Povo Asiático/genética , Família Aldeído Desidrogenase 1/genética , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Retinal Desidrogenase/genética , Predisposição Genética para Doença , Adulto , China , Sequenciamento de Nucleotídeos em Larga Escala , População do Leste Asiático
7.
Small ; : e2310781, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488770

RESUMO

Improving target versus off-target ratio in nanomedicine remains a major challenge for increasing drug bioavailability and reducing toxicity. Active targeting using ligands on nanoparticle surfaces is a key approach but has limited clinical success. A potential issue is the integration of targeting ligands also changes the physicochemical properties of nanoparticles (passive targeting). Direct studies to understand the mechanisms of active targeting and off-targeting in vivo are limited by the lack of suitable tools. Here, the biodistribution of a representative active targeting liposome is analyzed, modified with an apolipoprotein E (ApoE) peptide that binds to the low-density lipoprotein receptor (LDLR), using zebrafish embryos. The ApoE liposomes demonstrated the expected liver targeting effect but also accumulated in the kidney glomerulus. The ldlra-/- zebrafish is developed to explore the LDLR-specificity of ApoE liposomes. Interestingly, liver targeting depends on the LDLR-specific interaction, while glomerular accumulation is independent of LDLR and peptide sequence. It is found that cationic charges of peptides and the size of liposomes govern glomerular targeting. Increasing the size of ApoE liposomes can avoid this off-targeting. Taken together, the study shows the potential of the zebrafish embryo model for understanding active and passive targeting mechanisms, that can be used to optimize the design of nanoparticles.

8.
Heliyon ; 10(5): e27063, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495159

RESUMO

With the advancement of science and artificial intelligence, education is experiencing significant innovation. The adaptive learning system is emerging as a promising approach to achieving personalized learning. The cognitive model plays a crucial role as the fundamental rationale behind the adaptive learning system. Currently, there is no uniform and highly operational method for constructing cognitive models. This study adopts Interpretive Structural Modeling (ISM) as the foundational approach for constructing a cognitive model of solid geometry. Based on literature and expert opinions, 17 cognitive attributes of high school solid geometry were identified. Subsequently, a questionnaire survey involving 40 experts was conducted to establish the contextual relationships among these attributes. Applying the ISM method resulted in a seven-level model. This model was then revised based on expert opinions to create the final cognitive model, revealing three primary paths within the domain of high school solid geometry. This paper contends that the use of the ISM method for constructing cognitive models is effective and objective. The resulting cognitive model unveils the content structure of high school solid geometry, and provides an innovative perspective on the construction of cognitive models.

9.
Biomed Pharmacother ; 173: 116342, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430635

RESUMO

BACKGROUND: Neuroinflammation is responsible for neuropsychiatric dysfunction following acute brain injury and neurodegenerative diseases. This study describes how a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor FG-4592 prevents the lipopolysaccharide (LPS)-induced acute neuroinflammation in microglia. METHODS: The distribution of FG-4592 in mouse brain tissues was determined by collision-induced dissociation tandem mass spectrometry. Microglial activation in the hippocampus was analyzed by immunofluorescence. Moreover, we determined the activation of HIF-1 and nuclear factor-κB (NF-κB) signaling pathways, proinflammatory responses using molecular biological techniques. Transcriptome sequencing and BNIP3 silencing were conducted to explore signaling pathway and molecular mechanisms underlying FG-4592 anti-inflammatory activity. RESULTS: FG-4592 was transported into the brain tissues and LPS increased its transportation. FG-4592 promoted the expression of HIF-1α and induced the downstream gene transcription in the hippocampus. Administration with FG-4592 significantly inhibited microglial hyperactivation and decreased proinflammatory cytokine levels following LPS treatment in the hippocampus. The LPS-induced inflammatory responses and the NF-κB signaling pathway were also downregulated by FG-4592 pretreatment in microglial cells. Mechanistically, Venn diagram analysis of transcriptomic changes of BV2 cells identified that BNIP3 was a shared and common differentially expressed gene among different treatment groups. FG-4592 markedly upregulated the protein levels of BNIP3 in microglia. Importantly, BNIP3 knockdown aggravated the LPS-stimulated inflammatory responses and partially reversed the protection of FG-4592 against microglial inflammatory signaling and microglial activation in the mouse hippocampus. CONCLUSIONS: FG-4592 alleviates neuroinflammation through facilitating microglial HIF-1/BNIP3 signaling pathway in mice. Targeting HIF-PHD/HIF-1/BNIP3 axis is a promising strategy for the development of anti-neuroinflammation drugs.


Assuntos
NF-kappa B , Inibidores de Prolil-Hidrolase , Camundongos , Animais , NF-kappa B/metabolismo , Microglia/metabolismo , Inibidores de Prolil-Hidrolase/metabolismo , Doenças Neuroinflamatórias , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Transdução de Sinais , Fator 1 Induzível por Hipóxia/metabolismo
10.
Cell Death Dis ; 15(2): 129, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342917

RESUMO

Neural stem cells (NSCs) are critical for brain development and maintenance of neurogenesis. However, the molecular mechanisms that regulate NSC proliferation and differentiation remain unclear. Mysm1 is a deubiquitinase and is essential for the self-renewal and differentiation of several stem cells. It is unknown whether Mysm1 plays an important role in NSCs. Here, we found that Mysm1 was expressed in NSCs and its expression was increased with age in mice. Mice with Mysm1 knockdown by crossing Mysm1 floxed mice with Nestin-Cre mice exhibited abnormal brain development with microcephaly. Mysm1 deletion promoted NSC proliferation and apoptosis, resulting in depletion of the stem cell pool. In addition, Mysm1-deficient NSCs skewed toward neurogenesis instead of astrogliogenesis. Mechanistic investigations with RNA sequencing and genome-wide CUT&Tag analysis revealed that Mysm1 epigenetically regulated Id4 transcription by regulating histone modification at the promoter region. After rescuing the expression of Id4, the hyperproliferation and imbalance differentiation of Mysm1-deficient NSCs was reversed. Additionally, knockdown Mysm1 in aged mice could promote NSC proliferation. Collectively, the present study identified a new factor Mysm1 which is essential for NSC homeostasis and Mysm1-Id4 axis may be an ideal target for proper NSC proliferation and differentiation.


Assuntos
Células-Tronco Neurais , Proteases Específicas de Ubiquitina , Camundongos , Animais , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Endopeptidases/metabolismo , Transativadores/metabolismo , Diferenciação Celular/fisiologia , Células-Tronco Neurais/metabolismo , Proliferação de Células/genética
11.
Nutrition ; 121: 112365, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38377700

RESUMO

OBJECTIVES: The practicality and effectiveness of using the prognostic value of the neutrophil-to-albumin ratio (NAR) in evaluating patients with cancer remain unclear, and research is needed to fully understand its potential application in the cancer population. METHODS: The Kaplan-Meier method was used for survival analysis, and the log-rank test was employed for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the prognostic biomarkers, and Logistic regression analysis was conducted to investigate the relationship between NAR and 90-day outcomes and cachexia. RESULTS: The study included 14 682 patients with cancer, divided into discovery (6592 patients), internal validation (2820 patients), and external validation groups (5270 patients). Patients with high NAR had higher all-cause mortality than those with low NAR in the discovery (50.15% versus 69.29%, P < 0.001), internal validation (54.18% versus 70.91%, P < 0.001), and external validation cohorts (40.60% versus 66.68%, P < 0.001). In the discovery cohort, high NAR was observed to be independently associated with all-cause mortality in patients (HR 1.16, 95% CI 1.12-1.19; P < 0.001). Moreover, we validated the promising prognostic value of NAR as a predictor of survival in patients with cancer through internal validation (HR 1.21, 95% CI 1.16-1.27, P < 0.001) and external validation cohorts (HR 1.27, 95% CI 1.21-1.34, P < 0.001). Additionally, in the subgroup analysis by tumor type, high NAR was identified as a risk factor for most cancers, except for breast cancer. CONCLUSIONS: This study showed that NAR is a feasible and promising biomarker for predicting prognosis and cancer cachexia in cancer patients.


Assuntos
Neoplasias , Neutrófilos , Humanos , Prognóstico , Caquexia/patologia , Neoplasias/complicações , Neoplasias/patologia , Albuminas , Estudos de Coortes , Estudos Retrospectivos
12.
Cancer Metab ; 12(1): 3, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273418

RESUMO

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

14.
Chem Soc Rev ; 53(1): 317-360, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38073448

RESUMO

Gene therapy is on its way to revolutionize the treatment of both inherited and acquired diseases, by transferring nucleic acids to correct a disease-causing gene in the target cells of patients. In the fight against infectious diseases, mRNA-based therapeutics have proven to be a viable strategy in the recent Covid-19 pandemic. Although a growing number of gene therapies have been approved, the success rate is limited when compared to the large number of preclinical and clinical trials that have been/are being performed. In this review, we highlight some of the hurdles which gene therapies encounter after administration into the human body, with a focus on nucleic acid degradation by nucleases that are extremely abundant in mammalian organs, biological fluids as well as in subcellular compartments. We overview the available strategies to reduce the biodegradation of gene therapeutics after administration, including chemical modifications of the nucleic acids, encapsulation into vectors and co-administration with nuclease inhibitors and discuss which strategies are applied for clinically approved nucleic acid therapeutics. In the final part, we discuss the currently available methods and techniques to qualify and quantify the integrity of nucleic acids, with their own strengths and limitations.


Assuntos
Terapia Genética , Ácidos Nucleicos , Humanos , Técnicas de Transferência de Genes , Ácidos Nucleicos/genética , Pandemias , Animais , Mamíferos
15.
Inflamm Res ; 73(2): 243-252, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087077

RESUMO

AIMS: This study aimed to explore whether the obesity paradox exists in overall and specific cancers and to investigate the role of systemic inflammation in the obesity paradox. METHODS: The Cox proportional hazard model was used to explore the relationship between body mass index (BMI) and all-cause mortality. The mediated effect was used to investigate the proportion of systemic inflammation mediating the relationship between BMI and cancer survival risk. RESULTS: The survival probability showed a step-like increase with an increase in BMI regardless of pathological stage. Approximately 10.8%-24.0% of the overall association between BMI and all-cause mortality in cancer was mediated by inflammation. In the internal validation, we found evidence of the obesity paradox in all body composition obtained using BIA, with inflammation remaining an important mediating factor. Furthermore, we also validated the existence of the obesity paradox of cancer in NHANES. Systemic inflammation remains an important factor in mediating the association between BMI and prognosis in cancer patients. CONCLUSIONS: The obesity paradox is prevalent in most cancers, except for hepatic biliary cancer and breast cancer. Inflammation may be one of the true features of the obesity paradox in cancer.


Assuntos
Neoplasias , Obesidade , Humanos , Obesidade/epidemiologia , Obesidade/complicações , Paradoxo da Obesidade , Inquéritos Nutricionais , Estudos de Coortes , Inflamação/complicações , Neoplasias/epidemiologia , Neoplasias/complicações , Fatores de Risco
17.
J Am Chem Soc ; 146(1): 89-94, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38109262

RESUMO

The synthesis of crystalline polyphenylene covalent organic frameworks (COFs) was accomplished by linking fluorinated tris(4-acetylphenyl)benzene building units using aldol cyclotrimerization. The structures of the two COFs, reported here, were confirmed by powder X-ray diffraction techniques, Fourier transform infrared, and solid-state 13C CP/MAS NMR spectroscopy. The results showed that the COFs were porous and chemically stable in corrosive, harsh environments for at least 1 week. Accordingly, postsynthetically modified derivatives of these COFs using primary amines showed CO2 uptake from air and flue gas.

18.
Top Curr Chem (Cham) ; 382(1): 1, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38091203

RESUMO

Light-induced bioorthogonal reactions offer spatiotemporal control over selective biomolecular labeling. This review covers the recent advances in the design of photo-activatable reagents for bioorthogonal conjugation reactions in living systems. These reagents are stable in the absence of light, but transformed into reactive species upon light illumination, which then undergo rapid ligation reactions. The light wavelength has been tuned from ultraviolet to near infrared to enable efficient photo-activation in reactions in deep tissues. The most prominent photo-activatable reagents are presented, including tetrazoles, tetrazines, 9,10-phenanthrenequinone, diarylsydnones, and others. A particular focus is on the strategies for improving reaction kinetics and biocompatibility accomplished through careful molecular engineering. The utilities of these photo-activatable reagents are illustrated through a broad range of biological applications, including in vivo protein labeling, positron emission tomography (PET) imaging, responsive hydrogels, and fluorescence microscopy. The further development and optimization of these biocompatible photo-activatable reagents should lead to new chemical biology strategies for studying biomolecular structure and function in living systems.


Assuntos
Compostos Heterocíclicos , Indicadores e Reagentes , Microscopia de Fluorescência
19.
BMC Med ; 21(1): 512, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129842

RESUMO

BACKGROUND: Malnutrition is associated with poor overall survival (OS) in breast cancer patients; however, the most predictive nutritional indicators for the prognosis of patients with breast cancer are not well-established. This study aimed to compare the predictive effects of common nutritional indicators on OS and to refine existing nutritional indicators, thereby identifying a more effective nutritional evaluation indicator for predicting the prognosis in breast cancer patients. METHODS: This prospective study analyzed data from 776 breast cancer patients enrolled in the "Investigation on Nutritional Status and its Clinical Outcome of Common Cancers" (INSCOC) project, which was conducted in 40 hospitals in China. We used the time-dependent receiver operating characteristic curve (ROC), Kaplan-Meier survival curve, and Cox regression analysis to evaluate the predictive effects of several nutritional assessments. These assessments included the patient-generated subjective nutrition assessment (PGSGA), the global leadership initiative on malnutrition (GLIM), the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI). Utilizing machine learning, these nutritional indicators were screened through single-factor analysis, and relatively important variables were selected to modify the PNI. The modified PNI, termed the cholesterol-modified prognostic nutritional index (CPNI), was evaluated for its predictive effect on the prognosis of patients. RESULTS: Among the nutritional assessments (including PGSGA, GLIM, CONUT, NRI, and PNI), PNI showed the highest predictive ability for patient prognosis (time-dependent ROC = 0.58). CPNI, which evolved from PNI, emerged as the superior nutritional index for OS in breast cancer patients, with the time-dependent ROC of 0.65. It also acted as an independent risk factor for mortality (p < 0.05). Moreover, the risk of malnutrition and mortality was observed to increase gradually among both premenopausal and postmenopausal age women, as well as among women categorized as non-overweight, overweight, and obese. CONCLUSIONS: The CPNI proves to be an effective nutritional assessment tool for predicting the prognosis of patients with breast cancer.


Assuntos
Neoplasias da Mama , Desnutrição , Humanos , Feminino , Avaliação Nutricional , Estado Nutricional , Prognóstico , Neoplasias da Mama/diagnóstico , Estudos Prospectivos , Desnutrição/diagnóstico , Colesterol , Estudos Retrospectivos
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