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BACKGROUND: Researchers have paid little attention to the safety of drug use among community residents (CRs). Irrational use of drugs can lead to health risks. We investigated the situation of knowledge-attitude-practices (KAP) of CRs in Shenzhen (China) for safe use of drugs, and analyzed the main factors influencing drug use. METHODS: A multi-stage, random sampling method was used. We used a validated questionnaire to conduct an online questionnaire survey on the demographic characteristics and KAP of safe use of drugs of CRs in 10 administrative districts of Shenzhen City. The KAP score of safe use of drugs of CRs was analyzed. Influencing factors were identified using a single-factor chi-squared test and binary logistic regression analysis. RESULTS: A total of 7269 valid questionnaires were collected. The average scores of knowledge, attitude, and behavior were (9.08 ± 1.49) (possible range: 0-10), (37.82 ± 3.96) (possible range: 8-40), and (35.82 ± 4.56) (possible range: 8-40), respectively, indicating that they had a better grasp of safe use of drugs. Logistic regression analysis showed that sex, age, education level, occupation, monthly household income per capita, marital status, health status, and different sources of information were the main factors affecting the knowledge and behavior of safe use of drugs of CRs. In addition to the marital status variable, other variables also have a significant impact on attitude towards safe use of drugs of CRs. CONCLUSIONS: Male sex, lower education level, lower income level, average/poor self-rated health status, and single source of drug-use information were the main factors affecting safe use of drugs based on KAP theory. The government and medical workers should carry out various forms of drug-education activities for people with different needs, encourage CRs to learn safe use of drugs, and promote safe use of drugs by CRs through diverse information sources.
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Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , China , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven , Adolescente , AncianoRESUMEN
Concrescence is a rare dental anomaly in which two adjacent teeth are united only by their cementum. Concrescence most frequently occurs in molars, especially a third mandibular molar and a supernumerary tooth. It is rarely seen in the maxillary anterior teeth. This case report is the first in the literature which details the successful treatment of a concrescence between the maxillary central incisor and a supernumerary tooth through multidisciplinary therapy. The treatment plan included root canal treatment, endodontic microsurgery, and prosthodontic treatment.
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Microcirugia , Tratamiento del Conducto Radicular , Humanos , Microcirugia/métodos , Tratamiento del Conducto Radicular/métodos , Incisivo/anomalías , Incisivo/cirugía , Diente Supernumerario/cirugía , Diente Supernumerario/diagnóstico por imagen , Masculino , Femenino , AdultoRESUMEN
There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung bean were chelated with ferrous iron (MBP-Fe) and tested as a supplement in mice suffering from iron-deficiency anemia (IDA). Mice were randomly divided into seven groups: a group fed the normal diet, the IDA model group, and IDA groups treated with inorganic iron (FeSO4), organic iron (ferrous bisglycinate, Gly-Fe), low-dose MBP-Fe(L-MBP-Fe), high-dose MBP-Fe(H-MBP-Fe), and MBP mixed with FeSO4 (MBP/Fe). The different iron supplements were fed for 28 days via intragastric administration. The results showed that MBP-Fe and MBP/Fe had ameliorative effects, restoring hemoglobin (HGB), red blood cell (RBC), hematocrit (HCT), and serum iron (SI) levels as well as total iron binding capacity (TIBC) and body weight gain of the IDA mice to normal levels. Compared to the inorganic (FeSO4) and organic (Gly-Fe) iron treatments, the spleen coefficient and damage to liver and spleen tissues were significantly lower in the H-MBP-Fe and MBP/Fe mixture groups, with reparative effects on jejunal tissue. Gene expression analysis of the iron transporters Dmt 1 (Divalent metal transporter 1), Fpn 1 (Ferroportin 1), and Dcytb (Duodenal cytochrome b) indicated that MBP promoted iron uptake. These findings suggest that mung bean peptide-ferrous chelate has potential as a peptide-based dietary supplement for treating iron deficiency.
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Anemia Ferropénica , Disponibilidad Biológica , Compuestos Ferrosos , Hierro , Péptidos , Vigna , Animales , Vigna/química , Anemia Ferropénica/tratamiento farmacológico , Ratones , Compuestos Ferrosos/química , Péptidos/química , Hierro/química , Hierro/metabolismo , Masculino , Quelantes del Hierro/química , Hemoglobinas/metabolismo , Suplementos Dietéticos , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Modelos Animales de Enfermedad , GlicinaRESUMEN
Leukemia poses a significant clinical challenge due to its swift onset, rapid progression, and treatment-related complications. Tumor immune evasion, facilitated by immune checkpoints like programmed death receptor 1/programmed death receptor ligand 1 (PD-1/PD-L1), plays a critical role in leukemia pathogenesis and progression. In this review, we summarized the research progress and therapeutic potential of PD-L1 in leukemia, focusing on targeted therapy and immunotherapy. Recent clinical trials have demonstrated promising outcomes with PD-L1 inhibitors, highlighting their role in enhancing treatment efficacy. This review discusses the implications of PD-L1 expression levels on treatment response and long-term survival rates in leukemia patients. Furthermore, we address the challenges and opportunities in immunotherapy, emphasizing the need for personalized approaches and combination therapies to optimize PD-L1 inhibition in leukemia management. Future research prospects include exploring novel treatment strategies and addressing immune-related adverse events to improve clinical outcomes in leukemia. Overall, this review provides valuable insights into the role of PD-L1 in leukemia and its potential as a therapeutic target in the evolving landscape of leukemia treatment.
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Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Leucemia , Receptor de Muerte Celular Programada 1 , Humanos , Antígeno B7-H1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Leucemia/tratamiento farmacológico , Leucemia/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Inmunoterapia/métodosRESUMEN
Iron supplementation is a proactive approach to limit instances of iron deficiency anemia. This study is based on the enzymatic hydrolysis and fractionation of mung bean proteins (MBPs) followed by the determination of the Fe2+ chelating activities of these peptide-containing fractions. MBP-Fe complex was generated using a chemical chelation method and subsequently characterized. Following Sephadex G15 separation of MBPs, one of the fractions containing 10 different peptides, demonstrated maximum Fe2+ chelating activity of 39.97 ± 0.07 µg/mg. The sequences of these peptides were determined using liquid chromatography-tandem mass spectrometry. The Fe2+ ion content of the MBP-Fe complex was determined using X-ray photoelectron spectroscopy and 80% of the iron was found to be in Fe2+ oxidation state. After iron chelation, there was an increase in the peptide's particle size, with an average value of 550.67 ± 0.70 nm. This increase in size was attributed to the contributions of the amino proline and glycine, which extended the peptides to form the MBP-Fe complex. Finally, molecular docking studies revealed that Fe2+ mainly bound to carboxy-oxygen of glutamate and aspartate residues of mung bean peptides to form MBP-Fe complex. This research could serve as a scientific foundation for the development of dietary iron supplements using plant-derived peptides.
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Fabaceae , Vigna , Vigna/metabolismo , Hierro/química , Peso Molecular , Simulación del Acoplamiento Molecular , Péptidos/química , Quelantes , Fabaceae/químicaRESUMEN
BACKGROUND: Changes to speech and language are common symptoms across different subtypes of frontotemporal dementia (FTD). These changes affect the ability to communicate, impacting everyday functions. Accurately assessing these changes may help clinicians to track disease progression and detect response to treatment. OBJECTIVE: To determine which aspects of speech show significant change over time and to develop a novel composite score for tracking speech and language decline in individuals with FTD. METHOD: We recruited individuals with FTD to complete remote digital speech assessments based on a picture description task. Speech samples were analyzed to derive acoustic and linguistic measures of speech and language, which were tested for longitudinal change over the course of the study and were used to compute a novel composite score. RESULTS: Thirty-six (16 F, 20 M; M age = 61.3 years) individuals were enrolled in the study, with 27 completing a follow-up assessment 12 months later. We identified eight variables reflecting different aspects of language that showed longitudinal decline in the FTD clinical syndrome subtypes and developed a novel composite score based on these variables. The resulting composite score demonstrated a significant effect of change over time, high test-retest reliability, and a correlation with standard scores on various other speech tasks. CONCLUSION: Remote digital speech assessments have the potential to characterize speech and language abilities in individuals with FTD, reducing the burden of clinical assessments while providing a novel measure of speech and language abilities that is sensitive to disease and relevant to everyday function.
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Demencia Frontotemporal , Humanos , Persona de Mediana Edad , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/psicología , Habla/fisiología , Reproducibilidad de los Resultados , Lenguaje , Progresión de la EnfermedadRESUMEN
Pathological epithelialmesenchymal transition (EMT) has been shown to fulfill a key role in the development and progression of a variety of lung diseases. It has been demonstrated that the inflammatory microenvironment is a decisive factor in inducing pathological EMT. Hexacylated lipopolysaccharide (LPS) [or proacylated lipopolysaccharide (PLPS), which functions as proinflammatory lipopolysaccharide] is one of the most effective Tolllike receptor 4 (TLR4) agonists. Furthermore, the pentacylated and tetracylated form of lipopolysaccharide (or ALPS, which functions as antiinflammatory lipopolysaccharide) has been shown to elicit competitive antagonistic effects against the proinflammatory activity of PLPS. At present, it remains unclear whether LPS extracted from Bacteroides vulgatus (BVLPS) can prevent LPS extracted from Escherichia coli (ECLPS) from inducing pathological EMT. In the present study, A549 cells and C57BL/6 mice lung tissue were both induced by ECLPS (PLPS) and BVLPS (ALPS), either alone or in combination. The anticipated antiinflammatory effects of BVLPS were analyzed by examining the lung coefficient, lung pathology, A549 cell morphology and expression levels both of the inflammatory cytokines, IL1ß, IL6 and TNFα and of the EMT signature proteins, epithelial cadherin (Ecadherin), αsmooth muscle actin (αSMA) and vimentin. In addition, the expression levels of TLR4, bone morphogenic protein and activin membranebound inhibitor (BAMBI) and Snail were detected and the possible mechanism underlying how BVLPS may prevent ECLPSinduced EMT was analyzed. The results obtained showed that the morphology of the A549 cells was significantly polarized, the lung index was significantly increased, the alveolar structure was collapsed and the expression levels of IL1ß, IL6, TNFα, αSMA, vimentin, TLR4 and Snail in both lung tissue and A549 cells were significantly increased, whereas those of Ecadherin and BAMBI were significantly decreased. Treatment with BVLPS in combination with ECLPS was found to reverse these changes. In conclusion, the present study demonstrated that BVLPS is able to effectively prevent ECLPSinduced EMT in A549 cells and in mouse lung tissue and furthermore, the underlying mechanism may be associated with inhibition of the TLR4/BAMBI/Snail signaling pathway.
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Bacteroides , Transición Epitelial-Mesenquimal , Escherichia coli , Lipopolisacáridos , Pulmón , Lipopolisacáridos/química , Escherichia coli/química , Escherichia coli/fisiología , Bacteroides/química , Bacteroides/fisiología , Acilación , Inflamación , Células A549 , Pulmón/patología , Transducción de Señal , Humanos , Animales , Ratones , Ratones Endogámicos C57BLRESUMEN
Melanoma, the most aggressive form of cutaneous malignancy arising from melanocytes, is frequently characterized by metastasis. Despite considerable progress in melanoma therapies, patients with advanced-stage disease often have a poor prognosis due to the limited efficacy, off-target effects, and toxicity associated with conventional drugs. Nanotechnology has emerged as a promising approach to address these challenges with nanoparticles capable of delivering therapeutic agents specifically to the tumor microenvironment (TME). However, the clinical approval of nanomedicines for melanoma treatment remains limited, necessitating further research to develop nanoparticles with improved biocompatibility and precise targeting capabilities. This comprehensive review provides an overview of the current research on nano-drug delivery systems for melanoma treatment, focusing on liposomes, polymeric nanoparticles, and inorganic nanoparticles. It discusses the potential of these nanoparticles for targeted drug delivery, as well as their ability to enhance the efficacy of conventional drugs while minimizing toxicity. Furthermore, this review emphasizes the significance of interdisciplinary collaboration between researchers from various fields to advance the development of nanomedicines. Overall, this review serves as a valuable resource for researchers and clinicians interested in the potential of nano-drug delivery systems for melanoma treatment and offers insights into future directions for research in this field.
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Melanoma , Nanopartículas , Neoplasias Cutáneas , Humanos , Sistema de Administración de Fármacos con Nanopartículas , Melanoma/patología , Sistemas de Liberación de Medicamentos , Neoplasias Cutáneas/tratamiento farmacológico , Liposomas/farmacología , Microambiente Tumoral , NanomedicinaRESUMEN
OBJECTIVES: The aims of this paper is to search and explore publications in the field of pharmacovigilance for rare diseases and to visualize general information, research hotspots, frontiers and future trends in the field using the bibliometric tool CiteSpace to provide evidence-based evidence for scholars. METHODS: We searched the Web of Science Core Collection (WoSCC) for studies related to pharmacovigilance for rare diseases, spanning January 1, 1997-October 25, 2022. CiteSpace software was utilized to discuss countries/regions, institutions, authors, journals, and keywords. RESULTS: After screening, a total of 599 valid publications were included in this study, with a significant upward trend in the number of publications. These studies were from 68 countries/regions with the United States and the United Kingdom making the largest contributions to the field. 4,806 research scholars from 493 institutions conducted studies on pharmacovigilance for rare diseases. Harvard University and University of California were the top two productive institutions in the research field. He Dian of the Affiliated Hospital of Guizhou Medical University and Peter G.M. Mol of the University of Groningen, The Netherlands, were the two most prolific researchers. The Cochrane Database of Systematic Reviews and the New England Journal of Medicine were the journals with the highest number of articles and co-citation frequency respectively. Clinical trial, therapy and adverse event were the top three most cited keywords. CONCLUSIONS: Based on keywords co-occurrence analysis, four research topics were identified: orphan drug clinical trials, postmarketing ADR surveillance for orphan drugs, rare diseases and orphan drug management, and diagnosis and treatment of rare diseases. Immune-related adverse reactions and benefit-risk assessment of enzyme replacement therapy were at the forefront of research in this field. Treatment outcomes, early diagnosis and natural history studies of rare diseases may become hotspots for future research.
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Farmacovigilancia , Enfermedades Raras , Masculino , Humanos , Enfermedades Raras/tratamiento farmacológico , Revisiones Sistemáticas como Asunto , Bibliometría , Bases de Datos FactualesRESUMEN
Objective: Depression is a common mental health disorder and a major public health concern, significantly interfering with the lives of those affected. The complex clinical presentation of depression complicates symptom assessments. Day-to-day fluctuations of depression symptoms within an individual bring an additional barrier, since infrequent testing may not reveal symptom fluctuation. Digital measures such as speech can facilitate daily objective symptom evaluation. Here, we evaluated the effectiveness of daily speech assessment in characterizing speech fluctuations in the context of depression symptoms, which can be completed remotely, at a low cost and with relatively low administrative resources. Methods: Community volunteers (N = 16) completed a daily speech assessment, using the Winterlight Speech App, and Patient Health Questionnaire-9 (PHQ-9) for 30 consecutive business days. We calculated 230 acoustic and 290 linguistic features from individual's speech and investigated their relationship to depression symptoms at the intra-individual level through repeated measures analyses. Results: We observed that depression symptoms were linked to linguistic features, such as less frequent use of dominant and positive words. Greater depression symptomatology was also significantly correlated with acoustic features: reduced variability in speech intensity and increased jitter. Conclusions: Our findings support the feasibility of using acoustic and linguistic features as a measure of depression symptoms and propose daily speech assessment as a tool for better characterization of symptom fluctuations.
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Speech and language changes occur in Alzheimer's disease (AD), but few studies have characterized their longitudinal course. We analyzed open-ended speech samples from a prodromal-to-mild AD cohort to develop a novel composite score to characterize progressive speech changes. Participant speech from the Clinical Dementia Rating (CDR) interview was analyzed to compute metrics reflecting speech and language characteristics. We determined the aspects of speech and language that exhibited significant longitudinal change over 18 months. Nine acoustic and linguistic measures were combined to create a novel composite score. The speech composite exhibited significant correlations with primary and secondary clinical endpoints and a similar effect size for detecting longitudinal change. Our results demonstrate the feasibility of using automated speech processing to characterize longitudinal change in early AD. Speech-based composite scores could be used to monitor change and detect response to treatment in future research. HIGHLIGHTS: Longitudinal speech samples were analyzed to characterize speech changes in early AD.Acoustic and linguistic measures showed significant change over 18 months.A novel speech composite score was computed to characterize longitudinal change.The speech composite correlated with primary and secondary trial endpoints.Automated speech analysis could facilitate remote, high frequency monitoring in AD.
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AIMS: The strategy of blood pressure intervention in the elderly hypertensive patients (STEP) trial reported the cardiovascular benefit of intensive systolic blood pressure (SBP) control in patients with hypertension. The association between intensive SBP lowering and the risk of new-onset diabetes is unclear. This study aimed to evaluate the effect of intensive SBP lowering on the incidence of new-onset diabetes. METHODS AND RESULTS: Participants in STEP who had baseline fasting serum glucose (FSG) concentrations <7.0 mmol/L and no history of diabetes or hypoglycaemic medication use were included. The primary outcome was new-onset diabetes defined as the time to first occurrence of FSG concentrations ≥7.0 mmol/L. The secondary outcome was new-onset impaired fasting glucose (FSG: 5.6-6.9 mmol/L) in participants with normoglycemia. A competing risk proportional hazards regression model was used for analysis. The cohort comprised 5601 participants (mean age: 66.1 years) with a mean baseline SBP of 145.9 mmHg. Over a median follow-up of 3.42 years, 273 (9.6%) patients in the intensive SBP group (target, 110 to <130 mmHg) and 262 (9.5%) in the standard SBP group (target, 130 to <150 mmHg) developed diabetes (adjusted hazard ratio, 1.01; 95% confidence interval (CI), 0.86-1.20). The adjusted hazard ratio for the secondary outcome was 1.04 (95% CI, 0.91-1.18). The mean highest FSG concentration during the follow-up was 5.82 and 5.84 mmol/L in the intensive and standard groups, respectively. CONCLUSION: Intensive SBP lowering is not associated with an altered risk of new-onset diabetes or impaired fasting glucose in hypertensive patients. REGISTRATION: STEP ClinicalTrials.gov, number: NCT03015311.
There is no significant association between intensive SBP lowering and the risk of new-onset diabetes or impaired fasting glucose in hypertensive patients aged 6080 years.Our findings improve the understanding of the benefits and risks of implementing an intensive SBP treatment strategy in the clinic for older hypertensive patients.Our findings suggest that clinicians should continue to implement intensive SBP lowering strategies, without worrying about an altered risk of new-onset diabetes in their patients.
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Diabetes Mellitus , Hipertensión , Humanos , Anciano , Presión Sanguínea , Antihipertensivos/efectos adversos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Glucosa/farmacología , Glucosa/uso terapéutico , Factores de RiesgoRESUMEN
Sleep can affect nonalcoholic fatty liver disease (NAFLD). We investigated the association between sleep duration, sleep quality, and NAFLD. From January to December 2018, 1,073 patients (age: 37.94 ± 10.88, Body Mass Index (BMI): 22.85 ± 3.27) were enrolled. Pittsburgh Sleep Quality Index Questionnaire and Munich Chronotype Questionnaire were used to assess sleep duration, quality, and habits. Ultrasonography was used to diagnose NAFLD. Multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the risk of NAFLD by different types of sleep duration and sleep quality. No significant differences in sleep time, sleep quality, and sleep habits between the NAFLD and the non-NAFLD groups were observed (P > 0.05). There was no correlation between sleep duration and NAFLD in the whole cohort. After adjusting for age, exercise, fasting plasma glucose, and BMI, the group with long sleep duration showed a decreased risk of NAFLD in men (OR = 0.01, 95% CI: 0.001-0.27, P = 0.032). However, in all four adjusted models, no correlation between sleep duration, quality, and NAFLD was found in women. In conclusion, sleep duration was significantly and negatively associated with NAFLD in men but not women. Prospective studies are required to confirm this association.
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Aim: To determine the prognostic value of peripheral blood markers in advanced esophageal squamous cell carcinoma (ESCC) patients receiving programmed cell death protein 1 inhibitors plus chemotherapy as first-line therapy. Methods: A retrospective analysis of 54 patients with advanced ESCC was performed to assess 12 blood markers involving inflammation, nutrition, and tumor burden. Analysis of variance or Kruskal-Wallis tests were used to explore the difference in markers among different response to therapy. Survival curves were constructed using the Kaplan-Meier method. Multivariate Cox models were applied to identify independent predictors of outcome. Results: Patients who achieved response had significantly higher prealbumin, increased BMI, and lower hs-CRP levels at baseline compared with those who experienced disease progression. In the univariate analysis, ALI > 23.55, PNI > 45.175, NLR ≤ 5, and hs-CRP ≤ 6.7 mg/L were significantly associated with a better progression-free survival. Cox regression analysis revealed that ALI >23.55 (P = 0.037) and hs-CRP ≤6.7 mg/L (P = 0.043) were independently associated with superior PFS. Increased tumor abnormal protein (TAP) levels post two cycles was significantly associated with a worse prognosis (P = 0.004). Conclusions: A baseline signature of low ALI and high hs-CRP as well as an early increase in TAP in ESCC appear to be predictive of inferior PFS.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico , Supervivencia sin Progresión , Proteína C-Reactiva/análisis , Estudios Retrospectivos , PronósticoRESUMEN
Circumventing immune resistance and boosting immune response is the ultimate goal of cancer immunotherapy. Herein, we reported a tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle for specifically inducing immunogenic cell death (ICD) in combination with TAM depletion. A versatile ROS-cleavable camptothecin (CPT) prodrug (DCC) was synthesized through a thioacetal linker between CPT and the ROS generator cinnamaldehyde (CA), which could self-assemble into a uniform prodrug nanoparticle to realize a positive feedback loop of "ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation." This DCC was further modified with the TAM membrane (abbreviated as DCC@M2), which could not only target both primary tumors and lung metastasis nodules through VCAM-1/α4ß1 integrin interaction but also absorb CSF-1 secreted by tumor cells to disturb the interaction between TAMs and cancer cells. Our nanodecoy could effectively induce ICD cascade and deplete TAMs for priming tumor-specific effector T cell infiltration for antitumor immune response activation, which represents a versatile approach for cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle was fabricated for the first time. This ROS-cleavable camptothecin (CPT)/cinnamaldehyde (CA) prodrug (DCC) could self-assemble into a uniform nanoparticle to realize the positive feedback loop of "ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation." After TAM membrane coating, this system (DCC@M2) could not only target both primary tumors and lung metastatic nodules but also scavenge CSF-1 secreted by tumor cells for TAM depletion for sufficient chemotherapy-sensitized immunotherapy.
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Nanopartículas , Neoplasias , Profármacos , Camptotecina/farmacología , Línea Celular Tumoral , Humanos , Inmunoterapia , Factor Estimulante de Colonias de Macrófagos , Nanopartículas/uso terapéutico , Profármacos/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Purpose: The RAD51 family of genes, including RAD51 and the five RAD51-like paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3), are known to be crucially associated with DNA damage repair pathway. Increasing evidence indicated that RAD51 family members were implicated in breast cancer tumorigenesis. However, their biological roles and prognostic values in breast cancer have yet to be clarified. Methods: In this study, by using the Oncomine and GEPIA databases, we explored the transcriptional levels of RAD51 family members in breast cancer. Besides, the associations between RAD51 family expression and clinical features were evaluated by using the UALCAN database and Kaplan-Meier (KM) Plotter. We also analyzed the mutations of the RAD51 family and differentially altered genes from the cBioPortal database. Results: We found that RAD51 mRNA was significantly elevated in breast cancer samples than in normal tissues, while XRCC2 mRNA was downregulated. Besides, a remarkable correlation was detected between the expression of RAD51/RAD51B/XRCC2 genes and the breast cancer stage. Survival analysis utilizing the KM Plotter indicated that high RAD51 and XRCC3 mRNA was associated with a poor prognosis. Conversely, RFS data suggested that high levels of RAD51B/RAD51C/RAD51D/XRCC2 were associated with a favorable prognosis. Moreover, a high genetic variation rate of RAD51C (7%) was detected in breast cancer patients. Conclusion: Conclusively, we implied that RAD51 and XRCC3 might be potential targets for precision therapy in breast cancer and the RAD51B/RAD51C/RAD51D/XRCC2 genes have significant values for breast cancer prognosis.
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Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.
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Adenocarcinoma , Subunidades beta de Inhibinas/metabolismo , Neoplasias Pancreáticas , Adenocarcinoma/genética , Animales , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Metaloproteinasa 14 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/patología , Fenotipo , Pronóstico , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores , Neoplasias PancreáticasRESUMEN
Epithelial ovarian cancer (EOC) has a poor prognosis and high mortality rate; patients are easy to relapse with standard therapies. So, there is an urgent need to develop novel drugs. In this study, differentially expressed genes (DEGs) of EOC were identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Enrichment and protein-protein interaction (PPI) analyses were performed. The drug candidate which has the possibility to treat EOC was predicted by Connectivity Map (CMAP) databases. Moreover, molecular docking was selected to calculate the binding affinity between drug candidate and hub genes. The cytotoxicity of drug candidates was assessed by MTT and colony formation analysis, the proteins coded by hub genes were detected by Western blots, and apoptosis analysis was evaluated by flow cytometry. Finally, 296 overlapping DEGs (|log 2 fold change|>1; q-value <0.05), which were principally involved in the cell cycle (p < 0.05), and cyclin-dependent kinase 1 (CDK1) were screened as the significant hub gene from the PPI network. Furthermore, the 21 drugs were extracted from CMAPs; among them, piperlongumine (PL) showed a lower CMAP score (-0.80, -62.92) and was regarded as the drug candidate. Furthermore, molecular docking results between PL and CDK1 with a docking score of -8.121 kcal/mol were close to the known CDK1 inhibitor (-8.24 kcal/mol). Additionally, in vitro experiments showed that PL inhibited proliferation and induced apoptosis via targeting CDK1 in EOC SKOV3 cells. Our results reveal that PL may be a novel drug candidate for EOC by inhibiting cell cycle.
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Detecting early signs of cognitive decline is crucial for early detection and treatment of Alzheimer's Disease. Most of the current screening tools for Alzheimer's Disease represent a significant burden, requiring invasive procedures, or intensive and costly clinical testing. Recent findings have highlighted changes to speech and language patterns that occur in Alzheimer's Disease, and may be detectable prior to diagnosis. Automated tools to assess speech have been developed that can be used on a smartphone or tablet, from one's home, in under 10 min. In this study, we present the results of a study of older adults who completed a digital speech assessment task over a 6-month period. Participants were grouped according to those who scored above (N = 18) or below (N = 18) the recommended threshold for detecting cognitive impairment on the Montreal Cognitive Assessment (MoCA) and those with diagnoses of mild cognitive impairment (MCI) or early Alzheimer's Disease (AD) (N = 14). Older adults who scored above the MoCA threshold had better performance on speech composites reflecting language coherence, information richness, syntactic complexity, and word finding abilities. Those with MCI and AD showed more rapid decline in the coherence of language from baseline to 6-month follow-up, suggesting that this score may be useful both for detecting cognitive decline and monitoring change over time. This study demonstrates that automated speech assessments have potential as sensitive tools to detect early signs of cognitive impairment and monitor progression over time.
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INTRODUCTION: There are no available low-burden, point-of-care tests to diagnose, grade, and predict hepatic encephalopathy (HE). METHODS: We evaluated speech as a biomarker of HE in 76 English-speaking adults with cirrhosis. RESULTS: Three speech features significantly correlated with the following neuropsychiatric scores: speech rate, word duration, and use of particles. Patients with low neuropsychiatric scores had slower speech (22 words/min, P = 0.01), longer word duration (0.09 seconds/word, P = 0.01), and used fewer particles (0.85% fewer, P = 0.01). Patients with a history of overt HE had slower speech (23 words/min, P = 0.005) and longer word duration (0.09 seconds/word, P = 0.005). DISCUSSION: HE is associated with slower speech.