RESUMEN
Long noncoding RNAs (LncRNAs) have been gaining attention as potential therapeutic targets for lung cancer. In this study, we investigated the expression and biological behavior of lncRNA DARS-AS1, its predicted interacting partner miR-302a-3p, and ACAT1 in nonsmall cell lung cancer (NSCLC). The transcript level of DARS-AS1, miR-302a-3p, and ACAT1 was analyzed using qRT-PCR. Endogenous expression of ACAT1 and the expression of-and changes in-AKT/ERK pathway-related proteins were determined using western blotting. MTS, Transwell, and apoptosis experiments were used to investigate the behavior of cells. The subcellular localization of DARS-AS1 was verified using FISH, and its binding site was verified using dual-luciferase reporter experiments. The binding of DARS-AS1 to miR-302a-3p was verified using RNA co-immunoprecipitation. In vivo experiments were performed using a xenograft model to determine the effect of DARS-AS1 knockout on ACAT1 and NSCLC. lncRNA DARS-AS1 was upregulated in NSCLC cell lines and tissues and the expression of lncRNA DARS-AS1 was negatively correlated with survival of patients with NSCLC. Knockdown of DARS-AS1 inhibited the malignant behaviors of NSCLC via upregulating miR-302a-3p. miR-302a-3p induced suppression of malignancy through regulating oncogene ACAT1. This study demonstrates that the DARS-AS1-miR-302a-3p-ACAT1 pathway plays a key role in NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Acetil-CoA C-Acetiltransferasa/genética , Acetil-CoA C-Acetiltransferasa/metabolismoRESUMEN
The commonly used baseline-free Lamb wave damage identification methods often require a large amount of sensor data to eliminate the dependence on baseline signals. To improve the efficiency of damage localization, this paper proposes a new Lamb wave damage location method, namely the probabilistic exchanging-element time-reversal method (PEX-TRM), which is based on the exchanging-element time-reversal method (EX-TRM) and the probabilistic damage identification method. In this method, the influence of the damage wave packet migration on the correlation coefficient between the reconstructed signals of each sensing path and the initial excitation signal is analyzed, and the structure is divided into multiple regional units corresponding to the damage to locate damage. In addition, the influence of the number of sensing paths on the location accuracy is also analyzed. A method of damage probability imaging based on structural symmetry is proposed to enhance location accuracy in the case of sparse sensing paths. The experimental and simulation results verify that the method can achieve damage location with fewer excitation times. Moreover, this method can avoid the problem that the damage wave packet is difficult to extract, improve the efficiency of damage location, and promote the engineering application of the Lamb wave damage location method.
RESUMEN
OBJECTIVES: To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography (CBCT) images, and to compare and analyze the estimation results. METHODS: A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected. The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated. Three machine learning algorithms (K-nearest neighbor, ridge regression, and decision tree) and stepwise regression were used to establish four age estimation models. The coefficient of determination, mean error, root mean square error, mean square error and mean absolute error were computed and compared. A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed. RESULTS: The K-nearest neighbor model (R2=0.779) and the ridge regression model (R2=0.729) outperformed stepwise regression (R2=0.617), while the decision tree model (R2=0.494) showed poor fitting. The correlation heatmap demonstrated a monotonically negative correlation between age and the parameters including pulp volume, the ratio of pulp volume to hard tissue volume, and the ratio of pulp volume to tooth volume. CONCLUSIONS: Pulp volume and pulp volume proportion are closely related to age. The application of CBCT-based machine learning methods can provide more accurate age estimation results, which lays a foundation for further CBCT-based deep learning dental age estimation research.
Asunto(s)
Determinación de la Edad por los Dientes , Tomografía Computarizada de Haz Cónico , Pulpa Dental , Aprendizaje Automático , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Adolescente , Niño , Determinación de la Edad por los Dientes/métodos , Pulpa Dental/diagnóstico por imagen , Diente/diagnóstico por imagen , China , Incisivo/diagnóstico por imagen , Incisivo/anatomía & histología , Femenino , Masculino , AlgoritmosRESUMEN
The incidence of respiratory infections in the population is related to many factors, among which environmental factors such as air quality, temperature, and humidity have attracted much attention. In particular, air pollution has caused widespread discomfort and concern in developing countries. Although the correlation between respiratory infections and air pollution is well known, establishing causality between them remains elusive. In this study, by conducting theoretical analysis, we updated the procedure of performing the extended convergent cross-mapping (CCM, a method of causal inference) to infer the causality between periodic variables. Consistently, we validated this new procedure on the synthetic data generated by a mathematical model. For real data in Shaanxi province of China in the period of 1 January 2010 to 15 November 2016, we first confirmed that the refined method is applicable by investigating the periodicity of influenza-like illness cases, an air quality index, temperature, and humidity through wavelet analysis. We next illustrated that air quality (quantified by AQI), temperature, and humidity affect the daily influenza-like illness cases, and, in particular, the respiratory infection cases increased progressively with increased AQI with a time delay of 11 days.
RESUMEN
Psychological distress is a possible trigger contributing to food addiction, which is characterized by a loss of behavioral control and compulsive food intake. However, little is known about its underlying mechanisms. Self-control, an important self-regulation skill, may mediate the effect of psychological distress on food addiction. A cross-sectional survey was used to explore the direct relationship between psychological distress and food addiction, and the mediating role of self-control in this relationship. Food addiction, psychological distress, and self-control were evaluated using the Chinese versions of the Yale Food Addiction Scale 2.0, Depression-Anxiety-Stress Scale, and Self-control Scale, respectively. Correlation analyses showed that food addiction was positively correlated with psychological distress, but negatively related to self-control. Structural equation modeling revealed the mediating role of self-control in the relationship between food addiction and psychological distress. As a significant predictor of food addiction, psychological distress may induce food addiction directly or indirectly through the effect of self-control. These findings provide a deeper understanding of the relationship between psychological distress and food addiction, and the underlying mechanism. As such, psychological distress and self-control should be included in prevention and intervention strategies to address food addiction among college students.
Asunto(s)
Adicción a la Comida , Distrés Psicológico , Autocontrol , Estudios Transversales , Humanos , Estudiantes/psicologíaRESUMEN
Polylactic acid-glycolic acid (PLGA) has been widely used in bone tissue engineering due to its favorable biocompatibility and adjustable biodegradation. 3D printing technology can prepare scaffolds with rich structure and function, and is one of the best methods to obtain scaffolds for bone tissue repair. This review systematically summarizes the research progress of 3D-printed, PLGA-based scaffolds. The properties of the modified components of scaffolds are introduced in detail. The influence of structure and printing method change in printing process is analyzed. The advantages and disadvantages of their applications are illustrated by several examples. Finally, we briefly discuss the limitations and future development direction of current 3D-printed, PLGA-based materials for bone tissue repair.
Asunto(s)
Ingeniería de Tejidos , Andamios del Tejido , Huesos , Glicolatos , Poliésteres , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
BACKGROUD: It is important to expound the opposite clinical outcomes between children and adulthood for eradicate malaria. There remains unknown about the correlation between adaptive immune response and age-related in malaria. METHODS: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. RESULTS: The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group. CONCLUSIONS: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.
Asunto(s)
Inmunidad Adaptativa/inmunología , Malaria/inmunología , Plasmodium yoelii/inmunología , Factores de Edad , Animales , Modelos Animales de Enfermedad , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Malaria/mortalidad , Ratones , Ratones Endogámicos BALB C , Parasitemia/inmunología , Parasitemia/mortalidad , Plasmodium yoelii/clasificación , Receptor de Muerte Celular Programada 1/metabolismo , Transducción de Señal , Tasa de Supervivencia , Linfocitos T/citología , Linfocitos T/metabolismoRESUMEN
Polyhedral carbon nano-onions (CNOs) compared with traditional quasi-spherical CNOs are more stable and have less defects, which will greatly broaden their potential applications. However, there still lacks of a suitable synthetic method. Here, we developed a simple molecular fusion route and templet growth method by which polyhedral CNOs can be successfully synthesized. Characterization of the polyhedral CNOs by transmission electron microscopy, x-ray diffraction and Raman spectroscopy indicates that they have an ultra-high degree of graphitization and a large cavity diameter of about 10 nm, which results in their low density of 1.42 g cm-3. In addition, the deeper reaction mechanism of polyhedral CNOs growth was also elucidated. It was found that the channel structure and the absorption of the templet play the crucial role during the formation of polyhedral CNOs.
RESUMEN
Long non-coding RNAs (lncRNAs) have been identified as critical regulators in gastric cancer (GC) progression. However, whether lncRNA small nucleolar host gene 4 (SNHG4) functions in GC development remains unknown. In this study, the bio-functional role of SNHG4 and its potential mechanism on GC progression were systematically dissected. To investigate the role of SNHG4 in GC, we silenced SNHG4 using short hairpin RNAs (shRNAs) to perform loss-of-function assays. The results showed that SNHG4 expression in GC cells was at a higher level compared to normal gastric mucosal epithelial cells. Knockdown of SNHG4 dramatically suppressed proliferation, migration and invasion, and blocked cell cycle progression of GC cells. Moreover, knockdown of SNHG4 upregulated microRNA-204-5p (miR-204-5p) expression, whereas downregulated ribonucleotide reductase subunit M2 (RRM2) expression in GC cells. Dual-luciferase reporter assay results showed that miR-204-5p was a direct target of SNHG4. Additionally, knockdown of SNHG4 suppressed GC tumorigenesis in xenograft mouse models. Taken together, these data demonstrated that knockdown of SNHG4 suppressed GC development by targeting miR-204-5p.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Ratones , MicroARNs/genética , ARN Largo no Codificante/genética , Neoplasias Gástricas/genéticaRESUMEN
BACKGROUND: The COVID-19 pandemic is complex and is developing in different ways according to the country involved. METHODS: To identify the key parameters or processes that have the greatest effects on the pandemic and reveal the different progressions of epidemics in different countries, we quantified enhanced control measures and the dynamics of the production and provision of medical resources. We then nested these within a COVID-19 epidemic transmission model, which is parameterized by multi-source data. We obtained rate functions related to the intensity of mitigation measures, the effective reproduction numbers and the timings and durations of runs on medical resources, given differing control measures implemented in various countries. RESULTS: Increased detection rates may induce runs on medical resources and prolong their durations, depending on resource availability. Nevertheless, improving the detection rate can effectively and rapidly reduce the mortality rate, even after runs on medical resources. Combinations of multiple prevention and control strategies and timely improvement of abilities to supplement medical resources are key to effective control of the COVID-19 epidemic. A 50% reduction in comprehensive control measures would have led to the cumulative numbers of confirmed cases and deaths exceeding 590,000 and 60,000, respectively, by 27 March 2020 in mainland China. CONCLUSIONS: Multiple data sources and cross validation of a COVID-19 epidemic model, coupled with a medical resource logistic model, revealed the key factors that affect epidemic progressions and their outbreak patterns in different countries. These key factors are the type of emergency medical response to avoid runs on medical resources, especially improved detection rates, the ability to promote public health measures, and the synergistic effects of combinations of multiple prevention and control strategies. The proposed model can assist health authorities to predict when they will be most in need of hospital beds and equipment such as ventilators, personal protection equipment, drugs, and staff.
Asunto(s)
COVID-19/terapia , Atención a la Salud/organización & administración , Brotes de Enfermedades/prevención & control , Recursos en Salud/estadística & datos numéricos , Pandemias , China/epidemiología , Atención a la Salud/estadística & datos numéricos , Humanos , Modelos Teóricos , SARS-CoV-2 , Factores de TiempoRESUMEN
Sirtuin 5 (SIRT5) is a NAD+ -dependent class III protein deacetylase, and its role in prostate cancer has not yet been reported. Therefore, to explore the diagnosis and treatment of prostate cancer, we investigated the effect of SIRT5 on prostate cancer. Sirtuin 5 was assessed by immunohistochemistry in 57 normal and cancerous prostate tissues. We found that the tissue expression levels of SIRT5 in patients with Gleason scores ≥7 were significantly different from those in patients with Gleason scores <7 (P < .05, R > 0). Further, mass spectrometry and pathway screening experiments showed that SIRT5 regulated the activity of the mitogen-activated protein kinase (MAPK) pathway, which in turn modulated the expression of MMP9 and cyclin D1. Being a substrate of SIRT5, acetyl-CoA acetyltransferase 1 (ACAT1) was regulated by SIRT5. SIRT5 also regulated MAPK pathway activity through ACAT1. These results revealed that SIRT5 promoted the activity of the MAPK pathway through ACAT1, increasing the ability of prostate cancer cells to proliferate, migrate and invade. Overall, these results indicate that SIRT5 expression is closely associated with prostate cancer progression. Understanding the underlying mechanism may provide new targets and methods for the diagnosis and treatment of the disease.
Asunto(s)
Acetil-CoA C-Acetiltransferasa/metabolismo , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismo , Adulto , Anciano , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/patología , Unión ProteicaRESUMEN
Macrovascular complications develop in over a half of the diabetic individuals, resulting in high morbidity and mortality. This poses a severe threat to public health and a heavy burden to social economy. It is therefore important to develop effective approaches to prevent or slow down the pathogenesis and progression of macrovascular complications of diabetes (MCD). Oxidative stress is a major contributor to MCD. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) governs cellular antioxidant defence system by activating the transcription of various antioxidant genes, combating diabetes-induced oxidative stress. Accumulating experimental evidence has demonstrated that NRF2 activation protects against MCD. Structural inhibition of Kelch-like ECH-associated protein 1 (KEAP1) is a canonical way to activate NRF2. More recently, novel approaches, such as activation of the Nfe2l2 gene transcription, decreasing KEAP1 protein level by microRNA-induced degradation of Keap1 mRNA, prevention of proteasomal degradation of NRF2 protein and modulation of other upstream regulators of NRF2, have emerged in prevention of MCD. This review provides a brief introduction of the pathophysiology of MCD and the role of oxidative stress in the pathogenesis of MCD. By reviewing previous work on the activation of NRF2 in MCD, we summarize strategies to activate NRF2, providing clues for future intervention of MCD. Controversies over NRF2 activation and future perspectives are also provided in this review.
Asunto(s)
Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Angiopatías Diabéticas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , HumanosRESUMEN
After diagnosed in Wuhan, COVID-19 spread quickly in mainland China. Though the epidemic in regions outside Hubei in mainland China has maintained a degree of control, evaluating the effectiveness and timeliness of intervention strategies, and predicting the transmission risk of work resumption as well as lifting the lockdown in Hubei province remain urgent. A patch model reflecting the mobility of population between Hubei and regions outside Hubei is formulated, and parameterized based on multiple source data for Hubei and regions outside Hubei. The effective reproduction numbers for Hubei and regions outside Hubei are estimated as 3.59 and 3.26 before Jan 23rd, 2020, but decrease quickly since then and drop below 1 after Jan 31st and Jan 28th, 2020. It is predicted that the new infections in Hubei province will decrease to very low level in mid-March, and the final size is estimated to be about 68,500 cases. The simulations reveal that contact rate after work resumption or lifting the lockdown in Hubei plays a critical role in affecting the epidemic. If the contact rate could be kept at a relatively low level, work resumption starting as early as on March 2nd in Hubei province may not induce the secondary outbreak, and the daily new infectious cases can be controlled at a low level if the lockdown in Hubei is liftted after March 9th, otherwise both work resumption and lifting the lockdown in Hubei should be postponed.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/transmisión , Modelos Teóricos , Neumonía Viral/transmisión , Aislamiento Social , COVID-19 , China/epidemiología , Trazado de Contacto , Infecciones por Coronavirus/prevención & control , Predicción , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Política Pública/tendencias , SARS-CoV-2RESUMEN
Repeated outbreaks of Hand, foot and mouth disease (HFMD) infections have been observed in recent decades and dominated by various enteroviral serotypes. In particular, enterovirus 71 (EV-A71), coxsackievirus A16 (CV-A16) and coxsackievirus A6 (CV-A6) dominated the prevalence of HFMD infections alternatively in recent years with various outbreak sizes in Baoji, a city of Shaanxi Province in Northwest China. Estimating the reproduction number for various enteroviruses serotypes in northwest China (north temperate zone) and identification of cyclicity of HFMD infections are therefore an issue of great importance for future epidemics prediction and control. The basic/effective reproduction numbers for EV-A71, CV-A16 and CV-A6 were estimated based on daily new cases in 2010, 2011 and 2018, respectively, in which the corresponding pathogen dominated the epidemic. Two different methods based on serial interval were adopted and the basic reproduction number were estimated to be in the range of (1.33, 1.46) for CV-A16, (1.20, 1.29) for EV-A71, and (1.38, 1.59) for CV-A6, respectively. The estimated daily effective reproduction numbers significantly fluctuated before June or after July but varied mildly in (0.5,2) in around June to July for three serotypes. The weekly effective reproduction number for HFMD was estimated based on weekly new cases from year 2010 to 2018, and in most years it peaked in the range of (1.6,2.0) in February to March as well as in the range of (1.0,1.2) in September to October. The wavelet analysis based on the time series of HFMD cases from 2008 to 2018 showed obvious annual and semi-annual cyclicity, while the inter-annual cycles are infeasible. In this study we found that CV-A6 shows the greatest transmission ability among these three pathogens while EV-A71 exhibits the weakest ability of transmission, and moreover, the estimated values of basic reproduction number in northwest China are lower than those in Singapore, Hongkong and Guangdong, which may be due to different climatic circumstances.
Asunto(s)
Número Básico de Reproducción , Enfermedad de Boca, Mano y Pie , Modelos Teóricos , Periodicidad , China/epidemiología , Enterovirus/fisiología , Enterovirus Humano A/fisiología , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/transmisión , Enfermedad de Boca, Mano y Pie/virología , Humanos , SerotipificaciónRESUMEN
Estimating HIV incidence is crucial for monitoring the epidemiology of this infection, planning screening and intervention campaigns, and evaluating the effectiveness of control measures. However, owing to the long and variable period from HIV infection to the development of AIDS and the introduction of highly active antiretroviral therapy, accurate incidence estimation remains a major challenge. Numerous estimation methods have been proposed in epidemiological modeling studies, and here we review commonly-used methods for estimation of HIV incidence. We review the essential data required for estimation along with the advantages and disadvantages, mathematical structures and likelihood derivations of these methods. The methods include the classical back-calculation method, the method based on CD4+ T-cell depletion, the use of HIV case reporting data, the use of cohort study data, the use of serial or cross-sectional prevalence data, and biomarker approach. By outlining the mechanistic features of each method, we provide guidance for planning incidence estimation efforts, which may depend on national or regional factors as well as the availability of epidemiological or laboratory datasets.
Asunto(s)
Infecciones por VIH , Modelos Estadísticos , Terapia Antirretroviral Altamente Activa , Estudios de Cohortes , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Incidencia , PrevalenciaRESUMEN
BACKGROUND: The Guangxi Zhuang Autonomous Region bears a relatively high burden of HIV/AIDS infection. The number of accumulatively reported HIV/AIDS cases in Guangxi is the third highest among 31 provinces or Autonomous Region from 2004 to 2007, changed to the second highest between 2011 and 2013, then returned to the third highest again after 2014. We aim to estimate the new infections and evaluate the real-time HIV epidemic in Guangxi, China, in order to reveal the rule of HIV transmission. METHODS: Firstly, the number of annually reported HIV and AIDS cases, as well as the number of cases linked with CD4 data are extracted from the HIV/AIDS information system in China. Secondly, two CD4-staged models are formulated by linking the with-host information on CD4 level to between-host transmission and surveillance data. Thirdly, new HIV infections, diagnosis rates and undiagnosed infections over time are estimated by using Bayesian method and Maximum Likelihood Estimation method. RESULTS: The data reveal that the newly reported cases have been decreasing since 2011, while lots of cases are identified at late CD4 stage. The data fitted results indicate that both models can describe the trend of the epidemic well. The estimation results show that the new and undiagnosed infections began to decrease from the period2006 - 2008. However, the diagnosis probabilities/rates keep at a very low level, and there are still a large number of infections undiagnosed, most of which have a large probability to be identified at late CD4 stage. CONCLUSIONS: Our findings suggest that HIV/AIDS epidemic in Guangxi has been controlled to a certain extent, while the diagnosis rate still needs to be improved. More attentions should be paid to identify infections at their early CD4 stages. Meanwhile, comprehensive intervention measures should be continually strengthened in avoid of the rebound of new infections.
Asunto(s)
Epidemias , Infecciones por VIH/epidemiología , Teorema de Bayes , Recuento de Linfocito CD4 , China/epidemiología , Infecciones por VIH/sangre , Infecciones por VIH/prevención & control , HumanosRESUMEN
L-arginine (L-Arg), the precursor of nitric oxide (NO), plays multiple, important roles in nutrient metabolism and immune regulation. Hypoargininemia is one of the distinctive features of malaria patients in endemic areas. To understand the immunoregulatory function of L-Arg in malaria, we investigated the effects of L-Arg, pre- or/and post-treatment, on the cellular/humoral immune response during Plasmodium yoelii 17XL (P.y17XL) infection in DBA/2 mice. Populations of splenic CD4+T-bet+IFN-γ+ T cells (Th1), F4/80+ macrophages, CD4+GATA-3+IL-4+ T cells (Th2), B220+CD138+ plasmacytes and antibody-producing cells (IgG+/IgG1+-plasma cells) were assessed by flow cytometry. Pro-inflammatory cytokines and antibodies (IgG and IgG1) were quantified by immunoassays. We found that treatment with L-Arg significantly decreased parasitemia and shortened disease duration. Prophylactic treatment with L-Arg promotes an enhanced Th1 cell response during the early stages of P.y17XL infection, and treatment with L-Arg in the course of infection facilitates the later humoral immune response. Our findings suggest that treatment with L-Arg may decrease parasite burden and control the host's susceptibility to parasite synchronously by regulating host immune responses against P.y17XL, producing better outcomes for malaria infection. This implies that the supplementation of L-Arg may be a promising adjunctive therapy to reduce malaria-associated mortality in endemic areas.
Asunto(s)
Arginina/uso terapéutico , Malaria/tratamiento farmacológico , Plasmodium yoelii/inmunología , Animales , Anticuerpos Antiprotozoarios/biosíntesis , Anticuerpos Antiprotozoarios/inmunología , Células Productoras de Anticuerpos/efectos de los fármacos , Células Productoras de Anticuerpos/inmunología , Arginina/sangre , Citometría de Flujo , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/sangre , Interferón gamma/metabolismo , Malaria/inmunología , Malaria/prevención & control , Ratones , Ratones Endogámicos DBA , Óxido Nítrico/metabolismo , Parasitemia/tratamiento farmacológico , Parasitemia/prevención & control , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th2/citología , Células Th2/efectos de los fármacos , Células Th2/inmunologíaRESUMEN
BACKGROUND: The progression of Human Immunodeficiency Virus (HIV) within host includes typical stages and the Antiretroviral Therapy (ART) is shown to be effective in slowing down this progression. There are great challenges in describing the entire HIV disease progression and evaluating comprehensive effects of ART on life expectancy for HIV infected individuals on ART. METHODS: We develop a novel summative treatment benefit index (TBI), based on an HIV viral dynamics model and linking the infection and viral production rates to the Weibull function. This index summarizes the integrated effect of ART on the life expectancy (LE) of a patient, and more importantly, can be reconstructed from the individual clinic data. RESULTS: The proposed model, faithfully mimicking the entire HIV disease progression, enables us to predict life expectancy and trace back the timing of infection. We fit the model to the longitudinal data in a cohort study in China to reconstruct the treatment benefit index, and we describe the dependence of individual life expectancy on key ART treatment specifics including the timing of ART initiation, timing of emergence of drug resistant virus variants and ART adherence. CONCLUSIONS: We show that combining model predictions with monitored CD4 counts and viral loads can provide critical information about the disease progression, to assist the design of ART regimen for maximizing the treatment benefits.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/tendencias , Infecciones por VIH/tratamiento farmacológico , Esperanza de Vida/tendencias , Modelos Teóricos , Medicina de Precisión/tendencias , Fármacos Anti-VIH/inmunología , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4/métodos , Estudios de Cohortes , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Humanos , Estudios Longitudinales , Medicina de Precisión/métodos , Resultado del TratamientoRESUMEN
The public benefit of test-and-treat has induced a need to justify goodness for the public, and mathematical modeling studies have played a key role in designing and evaluating the test-and-treat strategy for controlling HIV/AIDS. Here we briefly and comprehensively review the essence of contemporary understanding of the test-and-treat policy through mathematical modeling approaches and identify key pitfalls that have been identified to date. While the decrease in HIV incidence is achieved with certain coverages of diagnosis, care and continued treatment, HIV prevalence is not necessarily decreased and sometimes the test-and-treat is accompanied by increased long-term cost of antiretroviral therapy (ART). To confront with the complexity of assessment on this policy, the elimination threshold or the effective reproduction number has been proposed for its use in determining the overall success to anticipate the eventual elimination. Since the publication of original model in 2009, key issues of test-and-treat modeling studies have been identified, including theoretical problems surrounding the sexual partnership network, heterogeneities in the transmission dynamics, and realistic issues of achieving and maintaining high treatment coverage in the most hard-to-reach populations. To explicitly design country-specific control policy, quantitative modeling approaches to each single setting with differing epidemiological context would require multi-disciplinary collaborations among clinicians, public health practitioners, laboratory technologists, epidemiologists and mathematical modelers.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/terapia , Modelos Biológicos , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/transmisión , Humanos , Atención al Paciente , Prevalencia , Estados UnidosRESUMEN
Rib segment, as one of the most widely used autologous boneresources for bone repair, is commonly isolated with an empty left in the defect. Although defective rib repair is thought to be unnecessary traditionally, it's of vital importance actually to promote rib regeneration for patients with better postoperative recovery and higher life quality. Comparative investigations on rabbit rib bone regeneration with and without graft were reported in this article. A segmental defect was performed on the 8th rib of 4-month-old male New Zealand rabbits. The mineralized collagen bone graft (MC) was implanted into the defect and evaluated for up to 12 weeks. The rib bone repair was investigated by using X-ray at 4, 8 and 12 weeks and histological examinations at 12 weeks after surgery, which showed a higher bone remodeling activity in the groups with MC implantation in comparison with blank control group, especially at the early stage of remodeling.