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1.
J Virol ; 97(7): e0061023, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37367229

RESUMO

Members of the Sarbecovirus subgenus of Coronaviridae have twice caused deadly threats to humans. There is increasing concern about the rapid mutation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has evolved into multiple generations of epidemic variants in 3 years. Broad neutralizing antibodies are of great importance for pandemic preparedness against SARS-CoV-2 variants and divergent zoonotic sarbecoviruses. Here, we analyzed the structural conservation of the receptor-binding domain (RBD) from representative sarbecoviruses and chose S2H97, a previously reported RBD antibody with ideal breadth and resistance to escape, as a template for computational design to enhance the neutralization activity and spectrum. A total of 35 designs were purified for evaluation. The neutralizing activity of a large proportion of these designs against multiple variants was increased from several to hundreds of times. Molecular dynamics simulation suggested that extra interface contacts and enhanced intermolecular interactions between the RBD and the designed antibodies are established. After light and heavy chain reconstitution, AI-1028, with five complementarity determining regions optimized, showed the best neutralizing activity across all tested sarbecoviruses, including SARS-CoV, multiple SARS-CoV-2 variants, and bat-derived viruses. AI-1028 recognized the same cryptic RBD epitope as the parental prototype antibody. In addition to computational design, chemically synthesized nanobody libraries are also a precious resource for rapid antibody development. By applying distinct RBDs as baits for reciprocal screening, we identified two novel nanobodies with broad activities. These findings provide potential pan-sarbecovirus neutralizing drugs and highlight new pathways to rapidly optimize therapeutic candidates when novel SARS-CoV-2 escape variants or new zoonotic coronaviruses emerge. IMPORTANCE The subgenus Sarbecovirus includes human SARS-CoV, SARS-CoV-2, and hundreds of genetically related bat viruses. The continuous evolution of SARS-CoV-2 has led to the striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma. Antibodies with broad activity across sarbecoviruses would be helpful to combat current SARS-CoV-2 mutations and longer term animal virus spillovers. The study of pan-sarbecovirus NAbs described here is significant for the following reasons. First, we established a structure-based computational pipeline to design and optimize NAbs to obtain more potent and broader neutralizing activity across multiple sarbecoviruses. Second, we screened and identified nanobodies from a highly diversified synthetic library with a broad neutralizing spectrum using an elaborate screening strategy. These methodologies provide guidance for the rapid development of antibody therapeutics against emerging pathogens with highly variable characteristics.


Assuntos
Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Anticorpos de Domínio Único , Animais , Humanos , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/química , Anticorpos Antivirais/metabolismo , Anticorpos Amplamente Neutralizantes/biossíntese , Anticorpos Amplamente Neutralizantes/química , Anticorpos Amplamente Neutralizantes/metabolismo , Quirópteros , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , Estrutura Terciária de Proteína , Modelos Moleculares , Ligação Proteica
2.
Biochem Genet ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347290

RESUMO

Fanconi anemia (FA) is the predominant hereditary syndrome of bone marrow failure (BMF), distinguished by impairments in DNA repair mechanisms. The deficiency in the FANC pathway, which governs DNA repair and replication rescue, results in aberrant responses to DNA damage in individuals with FA. The objective of this study is to examine the involvement of the FANC core complex in BMF and ascertain nucleolar homeostasis-related genes by conducting transcriptome analysis on primary hematopoietic stem cells obtained from FA patients with FANCA and FANCC variants. In the present study, we analyzed scRNA-seq data obtained from both healthy donors and individuals diagnosed with FA in order to investigate the phenomenon of cell-cell communication. Through the implementation of trajectory analysis, the differentiation pathways of several progenitor cell types, such as HSC cells transitioning into LMPP, N, M, B-prog, and E cells, were elucidated. Moreover, by scrutinizing the inferred interactions, notable disparities in cell-cell communication were observed between FA patients and their healthy counterparts. Our analysis has unveiled heightened interactions involving TNFSF13B, MIF, IL16, and COL4A2 in patients with FA. Furthermore, we have developed a prognostic model for predicting the outcome of acute myeloid leukemia (AML) which has exhibited remarkable predictive precision, with an AUC exceeding 0.83 at the 3- and 5-year intervals following the baseline assessment. In summary, the prognostic model that has been developed provides a valuable instrument for forecasting outcomes of AML by utilizing the genes identified through both single-cell and bulk transcriptome analyses.

3.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732182

RESUMO

Anthocyanins are water-soluble flavonoid pigments that play a crucial role in plant growth and metabolism. They serve as attractants for animals by providing plants with red, blue, and purple pigments, facilitating pollination and seed dispersal. The fruits of solanaceous plants, tomato (Solanum lycopersicum) and eggplant (Solanum melongena), primarily accumulate anthocyanins in the fruit peels, while the ripe fruits of Atropa belladonna (Ab) have a dark purple flesh due to anthocyanin accumulation. In this study, an R2R3-MYB transcription factor (TF), AbMYB1, was identified through association analysis of gene expression and anthocyanin accumulation in different tissues of A. belladonna. Its role in regulating anthocyanin biosynthesis was investigated through gene overexpression and RNA interference (RNAi). Overexpression of AbMYB1 significantly enhanced the expression of anthocyanin biosynthesis genes, such as AbF3H, AbF3'5'H, AbDFR, AbANS, and Ab3GT, leading to increased anthocyanin production. Conversely, RNAi-mediated suppression of AbMYB1 resulted in decreased expression of most anthocyanin biosynthesis genes, as well as reduced anthocyanin contents in A. belladonna. Overall, AbMYB1 was identified as a fruit-expressed R2R3-MYB TF that positively regulated anthocyanin biosynthesis in A. belladonna. This study provides valuable insights into the regulation of anthocyanin biosynthesis in Solanaceae plants, laying the foundation for understanding anthocyanin accumulation especially in the whole fruits of solanaceous plants.


Assuntos
Antocianinas , Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Antocianinas/biossíntese , Antocianinas/metabolismo , Frutas/metabolismo , Frutas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/genética , Interferência de RNA
4.
New Phytol ; 237(3): 885-899, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36271612

RESUMO

Artemisinin, a sesquiterpene lactone isolated from Artemisia annua, is in huge market demand due to its efficient antimalarial action, especially after the COVID-19 pandemic. Many researchers have elucidated that phytohormones jasmonic acid (JA) and abscisic acid (ABA) positively regulate artemisinin biosynthesis via types of transcription factors (TFs). However, the crosstalk between JA and ABA in regulating artemisinin biosynthesis remains unclear. Here, we identified a novel ABA- and JA-induced bHLH TF, AabHLH113, which positively regulated artemisinin biosynthesis by directly binding to the promoters of artemisinin biosynthetic genes, DBR2 and ALDH1. The contents of artemisinin and dihydroartemisinic acid increased by 1.71- to 2.06-fold and 1.47- to 2.23-fold, respectively, in AabHLH1113 overexpressed A. annua, whereas they decreased by 14-36% and 26-53%, respectively, in RNAi-AabHLH113 plants. Furthermore, we demonstrated that AabZIP1 and AabHLH112, which, respectively, participate in ABA and JA signaling pathway to regulate artemisinin biosynthesis, directly bind to and activate the promoter of AabHLH113. Collectively, we revealed a complex network in which AabHLH113 plays a key interrelational role to integrate ABA- and JA-mediated regulation of artemisinin biosynthesis.


Assuntos
Artemisia annua , Artemisininas , Ácido Abscísico/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Artemisininas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Angew Chem Int Ed Engl ; 62(16): e202218965, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36799716

RESUMO

Narrow-band emission is essential for applicable circularly polarized luminescence (CPL) active materials in ultrahigh-definition CP-OLEDs. One of the most promising classes of CPL active molecules, helicenes, however, typically exhibit broad emission with a large Stokes shift. We present, herein, a design strategy capitalizing on intramolecular donor-acceptor interactions between nitrogen and boron atoms to address this issue. 1,4-B,N-embedded configurationally stable single- and double helicenes were synthesized straightforwardly. Both helicenes show unprecedentedly narrow fluorescence and CPL bands (full width at half maximum between 17-28 nm, 0.07-0.13 eV) along with high fluorescence quantum yields (72-85 %). Quantum chemical calculations revealed that the relative localization of the natural transition orbitals, mainly on the rigid core of the molecule, and small values of root-mean-square displacements between S0 and S1 state geometries, contribute to the narrower emission.

6.
Cancer Control ; 29: 10732748221127826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36223407

RESUMO

OBJECTIVE: This study aimed to investigate the risk factors of venous thromboembolism (VTE) in admitted patients with lung carcinoma before surgery. METHODS: We conducted a retrospective case-control study of 94 preoperative lung cancer patients with VTE between January 2017 to December 2020. Each VTE patients was randomly matched with 2 control patients according to residence and gender. The clinical characteristics and related laboratory test results between the groups were compared by univariate analysis, while the risk factors of VTE in preoperative patients with lung cancer were analyzed using multivariate logistic regression analysis. RESULTS: Patients aged ≥60 years, a history of arrhythmia, homocysteine>15ummol/L, Fibrinogen (FIB) >4 g/L and D-dimer>500 ng/mL were found to be associated with an increased risk of VTE by univariate analysis. The multivariate logistic regression analysis revealed that age ≥60 years (OR=10.985), FIB >4 g/L (OR=8.861) and D-Dimer >500 ng/mL (OR=6.613) were independent risk factors for VTE in patients with lung carcinoma before surgery (P<.05). CONCLUSION: For preoperative patients with lung cancer, the independent risk factors of VTE included age ≥60 years, FIB >4 g/L and D-Dimer >500 ng/mL. As for these patients, prophylactic anticoagulant therapy should be considered before surgery.


Assuntos
Carcinoma , Neoplasias Pulmonares , Tromboembolia Venosa , Anticoagulantes , Estudos de Casos e Controles , Feminino , Fibrinogênio , Homocisteína , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Masculino , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
7.
BMC Gastroenterol ; 22(1): 347, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842604

RESUMO

BACKGROUND: Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma (NHL). Due to the rarity of the disease, it is important to create a predictive model that provides treatment and prognosis for patients with PGL and physicians. METHODS: A total of 8898 and 127 patients diagnosed with PGL were obtained from the SEER database and from our Cancer Center as training and validation cohorts, respectively. Univariate and multivariate Cox proportional hazards models were used to investigate independent risk factors for the construction of predictive survival nomograms, and a web nomogram was developed for the dynamic prediction of survival of patients with PGL. The concordance index (C-index), calibration plot, and receiver operating characteristics (ROC) curve were used to evaluate and validate the nomogram models. RESULTS: There were 8898 PGL patients in the SEER cohort, most of whom were married men over the age of 60, 16.1% of the primary tumors were localized in the antrum and pylori of the stomach, which was similar to the composition of 127 patients in the Chinese cohort, making both groups comparable. The Nomogram of overall survival (OS) was compiled based on eight variables, including age at diagnosis, sex, race, marital status, histology, stage, radiotherapy and chemotherapy. Cancer-specific survival (CSS) nomogram was developed with eight variables, including age at diagnosis, sex, marital status, primary tumor site, histology, stage, radiotherapy and chemotherapy. The C-index of OS prediction nomogram was 0.948 (95% CI: 0.901-0.995) in the validation cohort, the calibration plots showed an optimal match and a high area below the ROC curve (AUC) was observed in both training and validation sets. Also, we established the first web-based PGL survival rate calculator ( https://yangjinru.shinyapps.io/DynNomapp/ ). CONCLUSION: The web dynamic nomogram provided an insightful and applicable tool for evaluating PGL prognosis in OS and CSS, and can effectively guide individual treatment and monitoring.


Assuntos
Linfoma não Hodgkin , Nomogramas , Humanos , Linfoma não Hodgkin/terapia , Masculino , Prognóstico , Estudos Retrospectivos , Programa de SEER , Neoplasias Gástricas , Taxa de Sobrevida
8.
Support Care Cancer ; 30(5): 3745-3760, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35022884

RESUMO

BACKGROUND: Obesity and weight gain have been associated with poor disease-specific and health-related outcomes in breast cancer survivors (BCS). But the benefits of weight loss in managing BCS have not been elucidated. OBJECTIVE: To evaluate the beneficial effects of weight loss programs in randomized controlled trials on BCS. METHODS: We searched English databases PubMed, the Cochrane Library, EMBASE, Scopus, Web of Science, CINAHL, and Chinese databases China National Knowledge Infrastructure (CNKI), Weipu Information Chinese Periodical Service Platform (VIP), China Biomedical Literature Service System (SinoMed), and Wanfang from the inception to January 2021 and collected randomized controlled trials (RCTs) of weight loss programs for BCS. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. The data synthesis was performed on RevMan (version 5.3), and the publication bias was calculated with STATA (version 15.1). RESULTS: Ten RCTs were included in the meta-analysis. The current study showed that diet and exercise interventions resulted in significant improvements in body weight (MD = - 4.43 kg, 95%CI: - 6.23 to - 2.63, P < 0.00001), waist circumference (MD = - 2.81 cm, 95%CI: - 4.37 to - 1.26, P = 0.004), hip circumference (MD = - 3.01 cm, 95%CI: - 4.24 to - 1.77, P < 0.0001), body mass index (MD = - 1.69 kg/m2, 95%CI: - 2.16 to - 1.21, P < 0.00001), systolic blood pressure (MD = - 12.12 mmHg, 95%CI: - 18.97 to - 5.27), p = 0.0005), C-reactive protein (MD = - 1.83 mg/L, 95% CI: - 2.74 to - 0.91, p < 0.0001), body fat (MD = - 1.19 kg, 95%CI: - 1.75 to - 0.63, P < 0.001), fat mass (MD = - 2.29 kg, 95%CI: - 3.12 to - 1.46, P < 0.0001), and lean body mass (MD = - 2.15 kg, 95%CI: - 3.66 to - 0.65, P = 0.005). Alternatively, compared with the effects of control interventions, weight loss programs did not affect fat-free mass, total cholesterol, low-density leptin cholesterol, glucose, insulin, and leptin (P > 0.05). CONCLUSIONS: This review summarizes the benefits of weight loss programs for BCS. The results indicated that weight loss programs could significantly improve specific anthropometric outcomes but not affect biochemical indicators. Researchers should tailor weight loss interventions to the body fat status of BCS. Evidence to support the translation of effective weight loss intervention programs into wider-scale implementation is needed to be part of routine survivorship care.


Assuntos
Sobreviventes de Câncer , Neoplasias , Programas de Redução de Peso , Índice de Massa Corporal , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sobreviventes
9.
Nucleic Acids Res ; 48(9): 4681-4697, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32297952

RESUMO

The miRNA pathway has three segments-biogenesis, targeting and downstream regulatory effectors. We aimed to better understand their cellular control by exploring the miRNA-mRNA-targeting relationships. We first used human evolutionarily conserved sites. Strikingly, AGOs 1-3 are all among the top 14 mRNAs with the highest miRNA site counts, along with ANKRD52, the phosphatase regulatory subunit of the recently identified AGO phosphorylation cycle; and the AGO phosphorylation cycle mRNAs share much more than expected miRNA sites. The mRNAs for TNRC6, which acts with AGOs to channel miRNA-mediated regulatory actions onto specific mRNAs, are also heavily miRNA-targeted. In contrast, upstream miRNA biogenesis mRNAs are not, and neither are downstream regulatory effectors. In short, binding site enrichment in miRNA targeting machinery mRNAs, but neither upstream biogenesis nor downstream effector mRNAs, was observed, endowing a cellular capacity for intensive and specific feedback control of the targeting activity. The pattern was confirmed with experimentally determined miRNA-mRNA target relationships. Moreover, genetic experiments demonstrated cellular utilization of this capacity. Thus, we uncovered a capacity for intensive, and specific, feedback-regulation of miRNA targeting activity directly by miRNAs themselves, i.e. segment-specific feedback auto-regulation of miRNA pathway, complementing miRNAs pairing with transcription factors to form hybrid feedback-loop.


Assuntos
Proteínas Argonautas/metabolismo , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Proteínas Argonautas/genética , Sítios de Ligação , Linhagem Celular , Células-Tronco Embrionárias/metabolismo , Retroalimentação Fisiológica , Humanos , Fosforilação , RNA Mensageiro/química , RNA-Seq
10.
Arch Psychiatr Nurs ; 37: 10-17, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35337433

RESUMO

This study aimed to describe different patterns of self-management behaviors among clients with schizophrenia in China. Two hundred twenty-eight clients with schizophrenia living in eight communities of Beijing were investigated using the Self-Management Instrument for Persons with Schizophrenia and a Demographic and Clinical Characteristics Questionnaire. Cluster analysis was performed to categorize the data. Four distinct self-management behavior patterns and variables of clients associated with non-adherent self-management were identified. The self-management behaviors and demographic characteristics were similar in each pattern but different among patterns. These findings could guide the development of more personalized and cost-effective self-management interventions for different patterns of clients in the future.


Assuntos
Esquizofrenia , Autogestão , Estudos Transversais , Humanos , Adesão à Medicação , Esquizofrenia/terapia , Inquéritos e Questionários
11.
J Am Chem Soc ; 143(10): 3687-3692, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33651600

RESUMO

Herein we report the synthesis and characterization of anionic boron- and carbon-based Kekulé diradicaloids spanned by a p-phenylene bridge. In contrast to Thiele's hydrocarbon, a closed-shell singlet system, they show an appreciable population of the triplet state at room temperature, as evidenced by both NMR and EPR spectroscopy. Moreover, en route to these anionic boron- and carbon-based hetero-diradicaloids, the formation of an isolable diamino(4-diarylboryl-phenyl)methyl radical was observed.

12.
Support Care Cancer ; 29(11): 6943-6956, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33847828

RESUMO

PURPOSE: To systematically assess the efficacy and side effects of scalp cooling in patients with breast cancer. METHODS: A systematic literature search was conducted in October 2020 across Cochrane Library, PubMed, Embase, CINAHL, Web of Science, Scopus, and four Chinese databases (CNKI, Wanfang, SinoMed, and VIP database). Our review included all randomized controlled trials, cohort studies, and cross-sectional studies. Two authors independently searched databases, screened studies, extracted data, and evaluated each included study's methodological quality and risk bias. Meta-analysis was performed using Stata 15.1 software package and Revman 5.3 software, with estimates of scalp cooling effect and its side effects from pooled using a random-effects model. This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42020216224). RESULTS: In total, 755 articles were screened and data from 27 studies involving 2202 participants were used in the meta-analysis. Studies meeting inclusion and exclusion criteria were three randomized clinical trials, 12 cohort studies, and 12 cross-sectional studies. The effectiveness rate of using a scalp cooling device to protect hair was 61% (95% CI: 55 to 67%, I2 = 88%, P = 0.000). However, scalp cooling therapy's side effects are not be ignored, such as headache, dizziness, scalp pain, neck pain, feeling cold, heaviness of the head, skin rash, nausea, and overtightened strap. CONCLUSIONS: This review shows that scalp cooling devices can significantly improve the patients with breast cancer chemotherapy-induced alopecia, but the implications of its side effects provide guide for the implementation of this technology.


Assuntos
Neoplasias da Mama , Hipotermia Induzida , Alopecia/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Couro Cabeludo
13.
Int J Clin Pract ; 75(10): e14345, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33973320

RESUMO

AIM: To identify existing comorbidity measures and summarise their association with acute coronary syndrome (ACS) outcomes. METHODS: We searched published studies from MEDLINE (OVIDSP) and EMBASE from inception to March 2021, studies of the pre-specified conference proceedings from Web of Science since May 2017, and studies included in any relevant systematic reviews. Studies that reported no comorbidity measures, no association of comorbid burden with ACS outcomes, or only used a comorbidity measure as a confounder without further information were excluded. After independent screening by three reviewers, data extraction and risk of bias assessment of each included study was undertaken. Results were narratively synthesised. RESULTS: Of 4166 potentially eligible studies identified, 12 (combined n = 6 885 982 participants) were included. Most studies had a high risk of bias at quality assessment. Six different types of comorbidity measures were identified with the Charlson comorbidity index (CCI) the most widely used measure among studies. Overall, the greater the comorbid burden or the higher comorbidity scores recorded, the greater was the association with the risk of mortality. CONCLUSION: The review summarised different comorbidity measures and reported that higher comorbidity scores were associated with worse ACS outcomes. The CCI is the most widely measure of comorbid burden and shows additive value to clinical risk scores in use.


Assuntos
Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/epidemiologia , Comorbidade , Humanos , Prognóstico , Fatores de Risco
14.
South Med J ; 114(3): 174-179, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33655312

RESUMO

OBJECTIVES: This study explores sex differences in ischemic stroke hospitalization incidence, 30-day mortality, and 30-day readmission in a southwestern US medical center. METHODS: Ischemic stroke admissions in a regional medical center in the southwestern United States were obtained for a 6.5-year time frame (N = 1968). Logistic regression models examine the adjusted effects of sex on 30-day mortality and 30-day readmission outcomes among individuals hospitalized for ischemic stroke. RESULTS: Findings confirm that although women experience higher mortality than men (9.1% vs 6.7%), the sex disparity in mortality is explained by the age distribution of strokes. Women experience far more strokes and deaths because of stroke at older ages. No differences in principal procedure or 30-day readmission emerged. CONCLUSIONS: Men experienced higher stroke hospitalization incidence, although women exhibited higher 30-day mortality. Age composition explained sex differences in mortality, but higher male stroke hospitalization incidence represents a larger public health issue that suggests the need for behavioral change at the population level. No meaningful sex differences emerged in treatment, mortality, or readmission.


Assuntos
Disparidades nos Níveis de Saúde , Hospitalização/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Fatores Sexuais , Acidente Vascular Cerebral/mortalidade , Distribuição por Idade , Idoso , Feminino , Hospitais/estatística & dados numéricos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Sudoeste dos Estados Unidos/epidemiologia
15.
Angew Chem Int Ed Engl ; 60(44): 23656-23660, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34403564

RESUMO

In this communication, we demonstrate a novel approach to prepare a discrete dimer of chiral phthalocyanine (Pc) by exploiting the flexible molecular geometry of helicenes, which enables structural interlocking and strong aggregation tendency of Pcs. Synthesized [7]helicene-Pc hybrid molecular structure, zinc-[7]helicenocyanine (Zn-7HPc), exclusively forms a stable dimeric pair consisting of two homochiral molecules. The dimerization constants were estimated to be as high as 8.96×106  M-1 and 3.42×107  M-1 in THF and DMSO, respectively, indicating remarkable stability of dimer. In addition, Zn-7HPc exhibited chiral self-sorting behavior, which resulted in preferential formation of a homochiral dimer also in the racemic sample. Two phthalocyanine subunits in the dimeric form strongly communicate with each other as revealed by a large comproportionation constant and observation of an IV-CT band for the thermodynamically stable mixed-valence state.

16.
J Cell Biochem ; 121(2): 1923-1933, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31709617

RESUMO

Long noncoding RNAs (lncRNAs) are found to be aberrantly expressed and pose significant impacts in colorectal cancer (CRC), the most prevalent type malignancy in the gastrointestinal tract. This study aimed to find out the regulation of lncRNA EIF3J antisense RNA 1 (EIF3J-AS1) on CRC progression. Expressions of EIF3J-AS1, microRNA-3163 (miR-3163), and Yes-associated protein 1 (YAP1) in tissues and cells were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Association of EIF3J-AS1 with CRC prognosis was analyzed through the online bioinformatics tool GEPIA. The biological function of EIF3J-AS1 in CRC was investigated by Cell Counting Kit-8, colony formation, caspase-3 activity, and TUNEL staining. Competitive endogenous RNA (ceRNA) network of EIF3J-AS1/miR-3163/YAP1 was determined by luciferase reporter and RNA immunoprecipitation assays. Results showed that EIF3J-AS1 was upregulated in CRC tissues and cell lines, indicating poor prognosis of CRC patients. The silence of EIF3J-AS1 led to reduced proliferation and facilitated apoptosis of CRC cells. Mechanistcally, EIF3J-AS1 was upregulated by cAMP-response element-binding protein-binding protein-mediated histone H3 on lysine 27 acetylation (H3K27ac) at the promoter region, and EIF3J-AS1 upregulated YAP1 expression through sponging miR-3163 in CRC cells. In conclusion, we first found that H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through the miR-3163/YAP1 axis, which might potentially provide a novel molecular-targeted strategy for CRC treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Fatores de Iniciação em Eucariotos/genética , Histonas/química , MicroRNAs/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/metabolismo , Acetilação , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , RNA Antissenso/genética , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAP
17.
J Am Chem Soc ; 142(51): 21298-21303, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33315373

RESUMO

The interactions between auxochromic groups in π-conjugated functional molecules dictate their electronic properties. From the standpoint of potential applications, understanding and control of such interactions is a vital requirement for the material design. In this communication, we describe the design, synthesis, and functional properties of a novel class of helically chiral diimide molecules, namely, [n]HDI-OMe (n = 5, 6, and 7), in which two imide units are connected via an [n]helicene skeleton. The experimental results supported by quantum chemical calculations reveal that the helical backbone in these molecules offers not only through-bond but also through-space conjugation between imide groups, which leads to distinct optical and electrochemical properties when compared to the related [n]helicenes and rylene diimides.

18.
Support Care Cancer ; 28(4): 1579-1585, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31836940

RESUMO

BACKGROUND: The effect of dietary advice on malnutrition in cancer patients is unclear. The aim of this systematic review was to evaluate the effects of dietary advice in cancer patients who were malnourished or at risk of malnutrition. METHODS: Seven electronic databases were searched for randomized controlled trials (RCTs) of dietary counseling intervention in cancer patients with malnutrition or at risk of malnutrition. The studies were selected according to the inclusion and exclusion criteria and were critically appraised and abstracted by two researchers individually. Effect sizes were presented as weighted mean differences (WMD) or risk ratio (RR) with 95% confidence intervals (95%CI). RESULTS: Six RCTs (737 participants) were included in meta-analysis. Comparing to usual care, dietary advice given by dieticians could not reduce mortality (RR = 1.11, 95%CI = 0.95 to 1.29) and body weight (WMD = 4.28 kg, 95%CI = - 0.21 to 8.76 kg) in cancer patients who were malnourished or at risk of malnutrition, but it was associated with statistically significant improvements in energy intake (WMD = 230.23kCal, 95%CI: 171.49 to 288.98), and quality of life (WMD = 37.92, 95%CI: 23.14 to 52.70). CONCLUSIONS: There remains insufficient evidence to conclude the actual effect of dietary advice given by dieticians in malnourished patients with cancer. Meta-analysis suggested that dietary advice given by dietitians may have no effect on mortality and body weight in patients with cancer who are malnourished, but it may be effective for improving QoL and energy intake. Studies with adequate participants and a clear low risk of bias are required to improve accuracy and confidence of conclusions.


Assuntos
Desnutrição/dietoterapia , Desnutrição/etiologia , Neoplasias/dietoterapia , Neoplasias/metabolismo , Aconselhamento , Dieta , Dietética/métodos , Educação em Saúde , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Support Care Cancer ; 28(9): 4031-4041, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32328772

RESUMO

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is the most common and severe side effects brought by chemotherapeutics. The role of music interventions in relieving CINV is uncertain. The aim of this systematic review was to test the effects of music interventions on three categories of CINV. METHODS: A systematic search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Biomedical Database (CBM) in order to capture randomized controlled trials (RCTs) investigating the comparative efficacy of music interventions and others. Two investigators screened, sorted, and extracted the data, and appraised the risk of bias. All statistical analyses were performed using RevMan 5.3 software. RESULTS: The literature search yielded 608 studies of which only ten RCTs fulfilled the eligibility criteria with 632 patients retrieved. Although the duration, the frequency of interventions, and the type of selected music varied across studies, commonly used elements included music listening. Results showed that music interventions were associated with reducing the incidence of anticipatory CINV and lowering the severity of delayed vomiting (MD = - 0.65, 95% CI = - 1.08 to - 0.23). However, strongly controversial results existed in terms of reducing the incidence of acute and delayed CINV, the severity of acute CINV, the severity of delayed nausea, and improving patients' quality of life. CONCLUSIONS: Music interventions may effectively reduce the incidence of anticipatory CINV and relieve the severity of delayed vomiting in patients with chemotherapy based on limited data. However, the conclusion should be interpreted with caution and further research is required to design with large-scale and rigorous methods.


Assuntos
Náusea/terapia , Qualidade de Vida/psicologia , Vômito/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Música/psicologia , Náusea/induzido quimicamente , Vômito/induzido quimicamente
20.
Zhonghua Nan Ke Xue ; 26(9): 788-792, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33377700

RESUMO

OBJECTIVE: To investigate the effect and safety of the 3-week paclitaxel liposome protocol in the treatment of castration-resistant prostate cancer (CRPC). METHODS: This retrospective study included 40 cases of CRPC treated by the 3-week paclitaxel liposome protocol from February 2014 to February 2019, which involved intravenous injection of 10 mg dexamethasone in 100 ml normal saline on the first day and that of metoclopramide and panxi tora azole on the second day, followed by about 3 hours of intravenous drip of paclitaxel liposome at 135 mg/m2 for a course of 3 weeks. During the follow-up period, the patients received detection of the serum PSA level before treatment and chest x-ray and whole-body bone scan every six months. After two courses of treatment, the patients were observed for the changes in the serum PSA level, relief of bone pain, quality of survival, overall survival rate, overall survival time and toxic reactions. The protocol was continued unless the patient underwent progression, refused for unacceptable toxicity, or died. RESULTS: The patients were aged 59 to 79 (mean 68.80±5.67) years old, with the serum PSA level of (28.05 ± 3.22) µg/L at the baseline and (4.12 ± 0.23) µg/L after treatment. Thirty-eight of the patients were followed up for 3 to 33 (mean 12.2) months. PSA-based evaluation showed therapeutic effectiveness in 14 cases (35%), stable condition in 21 (52.5 %) and progression in 5 (12.5 %). Of the 18 patients with bone metastasis and pain, 16 (88.9 %) experienced relief of the symptoms and reduced the use of painkillers, with the bone pain scores of 5.20 ± 1.22 vs 2.79 ± 0.57 before and after treatment. By the end of the follow-up, the overall survival rate was 55.0% (22/40) and the median survival time was 17 months (95% CI: 13.4-24.6). During the treatment, no obvious adverse reactions were observed except for anemia in 1 case and hair loss in another. CONCLUSIONS: For the treatment of CRPC in China, the 3-week paclitaxel liposome protocol has the advantages of desirable safety, low toxicity, acceptable drug tolerance and improved quality of survival, but its curative effect needs to be verified with more randomized clinical trials with larger samples and longer follow-ups.


Assuntos
Lipossomos/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Neoplasias Ósseas/secundário , China , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
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