RESUMEN

Background: There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic. Methods: We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS. Conclusions: Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.

RESUMEN

PURPOSE: One of the most frequent side effects of radical prostatectomy (RP) is urinary incontinence. The primary cause of urine incontinence is usually thought to be impaired urethral sphincter function; nevertheless, the pathophysiology and recovery process of urine incontinence remains unclear. This study aimed to identify potential risk variables, build a risk prediction tool that considers preoperative urodynamic findings, and direct doctors to take necessary action to reduce the likelihood of developing early urinary incontinence. METHODS: We retrospectively screened patients who underwent radical prostatectomy between January 1, 2020 and December 31, 2023 at the First People 's Hospital of Nantong, China. According to nomogram results, patients who developed incontinence within three months were classified as having early incontinence. The training group's general characteristics were first screened using univariate logistic analysis, and the LASSO method was applied for the best prediction. Multivariate logistic regression analysis was carried out to determine independent risk factors for early postoperative urine incontinence in the training group and to create nomograms that predict the likelihood of developing early urinary incontinence. The model was internally validated by computing the performance of the validation cohort. The nomogram discrimination, correction, and clinical usefulness were assessed using the c-index, receiver operating characteristic curve, correction plot, and clinical decision curve. RESULTS: The study involved 142 patients in all. Multivariate logistic regression analysis following RP found seven independent risk variables for early urinary incontinence. A nomogram was constructed based on these independent risk factors. The training and validation groups' c-indices showed that the model had high accuracy and stability. The calibration curve demonstrates that the corrective effect of the training and verification groups is perfect, and the area under the receiver operating characteristic curve indicates great identification capacity. Using a nomogram, the clinical net benefit was maximised within a probability threshold of 0.01-1, according to decision curve analysis (DCA). CONCLUSION: The nomogram model created in this study can offer a clear, personalised analysis of the risk of early urine incontinence following RP. It is highly discriminatory and accurate, and it can help create efficient preventative measures and identify high-risk populations.

Asunto(s)

Nomogramas , Prostatectomía , Neoplasias de la Próstata , Incontinencia Urinaria , Humanos , Prostatectomía/efectos adversos , Incontinencia Urinaria/etiología , Incontinencia Urinaria/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Próstata/cirugía , Anciano , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Curva ROC , China/epidemiología

RESUMEN

BACKGROUND: This study aims to explore the molecular mechanism of lncRNA RP3-340B19.3 on breast cancer cell proliferation and metastasis and clinical significance of lncRNA RP3-340B19.3 for breast cancer. METHODS: The subcellular localization of lncRNA RP3-340B19.3 was identified using RNA fluorescence in situ hybridization (FISH). The expression of lncRNA RP3-340B19.3 in breast cancer cells, breast cancer tissues, as well as the serum and serum exosomes of breast cancer patients, was measured through quantitative RT-PCR. In the in vitro setting, we conducted experiments to observe the effects of RP3-340B19.3 on both cell migration and proliferation. This was achieved through the utilization of transwell migration assays as well as clone formation assays. Meanwhile, transwell migration assays and clone formation assays were used to observe the effects of MDA-MB-231-exosomes enriched in RP3-340B19.3 on breast cancer microenvironment cells MCF7 and BMMSCs. Additionally, western blotting techniques were used to assess the expression levels of proteins associated with essential cellular processes such as proliferation, apoptosis, and metastasis. In vivo, the impact of RP3-340B19.3 knockdown on tumour weight and volume was observed within a nude mice model. We aimed to delve into the intricate molecular mechanisms involving RP3-340B19.3 by using bioinformatics analysis, dual luciferase reporter gene experiments and western blotting. Moreover, the potential correlations between RP3-340B19.3 expression and various clinical pathological characteristics were analyzed. RESULTS: Our investigation revealed that RP3-340B19.3 was expressed in both the cytoplasm and nucleus, with a noteworthy increase in breast cancer cells. Notably, we found that RP3-340B19.3 exerted a promoting influence on the proliferation and migration of breast cancer cells, both in vitro and in vivo. MDA-MB-231-exosomes enriched in RP3-340B19.3 promoted the proliferation and migration of MCF7 and BMMSCs in vitro. Mechanistically, RP3-340B19.3 demonstrated the capability to modulate the expression of MORC4 by forming a complex with miR-4510. This interaction subsequently triggered the activation of the NF-κB and Wnt-ß-catenin signaling pathways. Furthermore, our study highlighted the potential diagnostic utility of RP3-340B19.3. We discovered its presence in the serum and exosomes of breast cancer patients, showing promising efficacy as a diagnostic marker. Notably, the diagnostic potential of RP3-340B19.3 was particularly significant in relation to distinguishing between different pathological types of breast cancer and correlating with tumour diameter. CONCLUSION: Our findings establish that RP3-340B19.3 plays a pivotal role in driving the proliferation and metastasis of breast cancer. Additionally, exosomes enriched in RP3-340B19.3 could influence MCF7 and BMMSCs in tumour microenvironment, promoting the progression of breast cancer. This discovery positions RP3-340B19.3 as a prospective novel candidate for a tumour marker, offering substantial potential in the realms of breast cancer diagnosis and treatment strategies.

RESUMEN

BACKGROUND: We have developed and validated methods for the determination of three major tryptophan metabolites metabolized by the kynurenine pathway, namely kynurenine (KYN), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid (3-HAA). KYN and 3-HK were determined using RP-HPLC-UV, and 3-HAA using RP-HPLC-FL. We then developed a comparative method based on CE-UV. The developed methods were validated and 36 samples of human brain glioma tissue homogenates were assayed in all 4 grades of malignancy, and the concentration levels of assayed metabolites were compared with available clinical data. RESULTS: Each of the methods is characterized by high precision, accuracy and repeatability, and the determined LOQ values indicate the possibility of performing quantitative analysis on the available samples of human glioma tumors (36 samples in grades G1-G4). The concentration values of selected metabolites obtained using HPLC methods were subjected to statistical analysis and preliminary clinical data processing. We found statistically significant differences in the concentrations of KYN, 3-HK and 3-HAA between the various grades of the disease, and characterized these differences more precisely by means of the Dunn-Bonferroni post hoc test. We did not find that the patient's environment or habits significantly affected the metabolites concentration of the study samples population. In addition, we showed a high positive correlation between KYN, 3-HK and 3-HAA, which appears to be a characteristic that describes metabolic changes of Trp in relation to KYN, 3-HK and 3-HAA, and indicates potential diagnostic value. SIGNIFICANCE: The preliminary studies carried out contribute new knowledge on the molecular basis of human brain glioma. They also provide valuable information useful for the development of glioma diagnostics, differentiation of disease grades and assessment of the patient's condition. The obtained relationships between metabolite concentrations and the grade of malignancy of the disease and correlations between metabolite concentrations constitute the basis for further broader biochemical and clinical analysis.

Asunto(s)

Neoplasias Encefálicas , Glioma , Quinurenina , Triptófano , Humanos , Triptófano/metabolismo , Triptófano/análisis , Glioma/metabolismo , Cromatografía Líquida de Alta Presión , Quinurenina/metabolismo , Quinurenina/análogos & derivados , Quinurenina/análisis , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Encefálicas/metabolismo , Ácido 3-Hidroxiantranílico/metabolismo , Ácido 3-Hidroxiantranílico/análisis , Adulto , Anciano

RESUMEN

The efficacious treatment of muscle and joint pain relies heavily on etofenamate (ETO) and benzyl nicotinate (BN), which possess robust anti-inflammatory and pain-relieving properties when paired with methylparaben (MP) or benzyl alcohol (BA). In this study, we have established and validated innovative RP-UPLC methods for assessing ETO and BN in the presence of MP or BA in their dosage forms, employing eight green tools to evaluate their eco-friendliness and effectiveness. Reversed phase-ultra-performance liquid chromatography (RP-UPLC) technique employs a flow rate of 0.3 mL/min on Waters Acquity UPLC BEH Column (C18, 1.7 µm, 100 mm × 2.1 mm), detection at 254 nm using a photo diode array (PDA) detector and mobile phase of 0.05 M KH2PO4 buffer, acetonitrile, and methanol (50:15:35, v/v/v) adjusted pH 6.0 with 0.2% triethylamine. For ETO, BN, MP, and BA, the calibration curves were linear and ranged from 0.005 to 1.0, from 0.001 to 0.2, from 0.002 to 0.08, and from 0.0001 to 0.1 mg/mL, respectively. The correlation value was 0.9999, and the accuracy findings ranged from 98.81% to 100.56%. Consequently, the methodology has been successfully implemented in assay testing for the pharmaceuticals in the presence of the MP or BA, demonstrating the high selectivity of these approaches. The present study presents the Blue Applicability Grade Index (BAGI), an innovative approach that complements green metrics in practical white analytical chemistry. According to the International Council for Harmonisation (ICH) criteria, the procedures were effectively validated.

RESUMEN

Due to its high polyphenol content, black rice plays a significant role in good nutrition; however, these antioxidant compounds are affected by heat treatments required for the rice consumption. The aim of this work was to investigate how cooking affects the composition of Artemide black rice, comparing innovative methods, such as sous vide, with traditional domestic techniques (risotto and pilaf). Proteins and ashes were not affected by cooking, except for pilaf rice, where a 42 % ashes decrease was observed; fiber content increased after all cooking methods, reaching a 29 % increase in the risotto. Antioxidant activity, total polyphenols, anthocyanins and proanthocyanidins were reduced on average of 40 %, 34 %, 43 % and 39 %, respectively. Individual anthocyanins decreased, while phenolic acids and other flavonoids presented different behaviours, also depending if considered in their free or bound form. Cyanidin-3-O-glucoside was reduced up to 56 % in the sous vide cooked rice at 99 °C, and only by 45 % and 37 % in the risotto and sous vide cooked rice at 89 °C, respectively. Traditional risotto preparation and the innovative sous vide cooking at 89 °C also maintained the highest antioxidant polyphenols content, saving 63 % of the antioxidant activity in respect to the raw black rice. Concluding, these last techniques can be suggested for a better preservation of bioactive compounds.

Asunto(s)

Antocianinas , Antioxidantes , Culinaria , Oryza , Polifenoles , Oryza/química , Culinaria/métodos , Antioxidantes/análisis , Antocianinas/análisis , Polifenoles/análisis , Fibras de la Dieta/análisis , Calor , Proantocianidinas/análisis , Glucósidos/análisis , Hidroxibenzoatos/análisis , Valor Nutritivo

RESUMEN

[This corrects the article DOI: 10.3389/fonc.2024.1360404.].

RESUMEN

Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes. Among the ultra-rare and recently discovered genes is ARSG, coding for the lysosomal sulfatase Arylsulfatase G. This subtype was assigned as "USH IV" with a late onset of RP and usually late-onset progressive SNHL without vestibular involvement. Here, we describe nine new subjects and the clinical description of four cases with the USH IV phenotype bearing seven novel and two known pathogenic variants. Functional experiments indicated the complete loss of sulfatase enzymatic activity upon ectopic expression of mutated ARSG cDNA. Interestingly, we identified a homozygous missense variant, p.(Arg99His), previously described in dogs with neuronal ceroid lipofuscinosis. Our study expands the genetic landscape of ARSG-USH IV and the number of known subjects by more than 30%. These findings highlight that USH IV likely has been underdiagnosed and emphasize the need to test molecularly unresolved subjects with deafblindness syndrome. Finally, testing of ARSG should be considered for the genetic work-up of apparent isolated inherited retinal diseases.

RESUMEN

The tumor suppressor p53 and its antagonists MDM2 and MDM4 integrate stress signaling. For instance, dysbalanced assembly of ribosomes in nucleoli induces p53. Here, we show that the ribosomal protein L22 (RPL22; eL22), under conditions of ribosomal and nucleolar stress, promotes the skipping of MDM4 exon 6. Upon L22 depletion, more full-length MDM4 is maintained, leading to diminished p53 activity and enhanced cellular proliferation. L22 binds to specific RNA elements within intron 6 of MDM4 that correspond to a stem-loop consensus, leading to exon 6 skipping. Targeted deletion of these intronic elements largely abolishes L22-mediated exon skipping and re-enables cell proliferation, despite nucleolar stress. L22 also governs alternative splicing of the L22L1 (RPL22L1) and UBAP2L mRNAs. Thus, L22 serves as a signaling intermediate that integrates different layers of gene expression. Defects in ribosome synthesis lead to specific alternative splicing, ultimately triggering p53-mediated transcription and arresting cell proliferation.

Asunto(s)

Empalme Alternativo , Exones , Precursores del ARN , Proteínas Ribosómicas , Proteína p53 Supresora de Tumor , Proteínas Ribosómicas/metabolismo , Proteínas Ribosómicas/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Humanos , Exones/genética , Precursores del ARN/metabolismo , Precursores del ARN/genética , Empalme Alternativo/genética , Nucléolo Celular/metabolismo , Proliferación Celular , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Unión Proteica , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Ribosomas/metabolismo , Estrés Fisiológico/genética , Proteínas de Unión al ARN

RESUMEN

BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Asunto(s)

Electrorretinografía , Proteínas del Ojo , Proteínas Asociadas a Microtúbulos , Tomografía de Coherencia Óptica , Agudeza Visual , Distrofia Macular Viteliforme , Humanos , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Adulto , Persona de Mediana Edad , Proteínas del Ojo/genética , Agudeza Visual/fisiología , Distrofia Macular Viteliforme/genética , Distrofia Macular Viteliforme/fisiopatología , Distrofia Macular Viteliforme/diagnóstico , Proteínas Asociadas a Microtúbulos/genética , Campos Visuales/fisiología , China/epidemiología , Adulto Joven , Pruebas del Campo Visual , Linaje , Adolescente , Fenotipo , Mutación , Degeneración Macular/genética , Degeneración Macular/diagnóstico , Degeneración Macular/fisiopatología , Pueblo Asiatico/genética , Anciano , Pueblos del Este de Asia

RESUMEN

BACKGROUND: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies. METHODS: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023. RESULTS: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9-48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention. CONCLUSIONS: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.

RESUMEN

A simple, Accurate, precise method was developed for the estimation of the Lorlatinib in API form and Marketed pharmaceutical dosage form by RP-HPLC. Chromatogram was run through Hypersil C18 (4.6mm×150mm, 5µm) Particle size Column and Mobile phase containing Methanol and Water taken in the ratio of 25: 75% v/v was pumped through column at a flow rate of 1.0 ml/min. Temperature was maintained at 38ºC. Optimized wavelength selected was 310 nm. Retention times of Lorlatinib were found to be 3.513 minutes respectively. The %RSD for the Repeatability and Intermediate Precision of the Lorlatinib were found to be within limits. %Recovery was obtained 98.96% and it was found to be within the limits for Lorlatinib respectively. The LOD, LOQ values obtained from regression equations of Lorlatinib were 0.332µg/ml and 1.0078 µg/ml respectively. Regression equation of Lorlatinib was found to be y = 39948x + 16821 respectively. The Retention times was decreased and run time was decreased, so the method developed was simple and economical that can be adopted in regular Quality control test in Industries.

Asunto(s)

Aminopiridinas , Lactamas Macrocíclicas , Lactamas , Pirazoles , Cromatografía Líquida de Alta Presión/métodos , Aminopiridinas/análisis , Pirazoles/análisis

RESUMEN

BACKGROUND: Metastasis is the major cause of colorectal cancer (CRC) mortality. Emerging evidence suggests that long noncoding RNAs (lncRNAs) drive cancer metastasis and that their regulatory pathways could be targeted for preventing metastasis. However, the underlying mechanisms of lncRNAs in CRC metastasis remain poorly understood. METHODS: Microarray analysis was used to screen for differentially expressed lncRNAs. Transwell assays, fibronectin cell adhesion assays, and mouse metastasis models were utilized to evaluate the metastatic capacities of CRC in vitro and in vivo. Chromatin isolation by RNA purification, chromatin immunoprecipitation and chromosome conformation capture were applied to investigate the underlying mechanism involved. qRT‒PCR and transmission electron microscopy were performed to confirm macrophage polarization and the presence of cancer-derived exosomes. RESULTS: The lncRNA RP11-417E7.1 was screened and identified as a novel metastasis-associated lncRNA that was correlated with a poor prognosis. RP11-417E7.1 enhances the metastatic capacity of CRC cells in vivo and in vitro. Mechanistically, RP11-417E7.1 binding with High mobility group A1 (HMGA1) promotes neighboring thrombospondin 2 (THBS2) transcription via chromatin loop formation between its promoter and enhancer, which activates the Wnt/ß-catenin signaling pathway and facilitates CRC metastasis. Furthermore, exosomes derived from CRC cells transport THBS2 into macrophages, thereby inducing the M2 polarization of macrophages to sustain the prometastatic microenvironment. Notably, netropsin, a DNA-binding drug, suppresses chromatin loop formation mediated by RP11-417E7.1 at the THBS2 locus and significantly inhibits CRC metastasis in vitro and in vivo. CONCLUSIONS: This study revealed the novel prometastatic function and mechanism of the lncRNA RP11-417E7.1, which provides a potential prognostic indicator and therapeutic target in CRC.

Asunto(s)

Neoplasias Colorrectales , Exosomas , Macrófagos , ARN Largo no Codificante , Vía de Señalización Wnt , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Humanos , Ratones , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Exosomas/metabolismo , Macrófagos/metabolismo , Metástasis de la Neoplasia , Masculino , Femenino , Línea Celular Tumoral , Pronóstico , beta Catenina/metabolismo , Regulación Neoplásica de la Expresión Génica

RESUMEN

PURPOSE: To provide data on radiation exposure in paediatric interventional cardiology procedures, addressing the scarcity of valuable Local Diagnostic Reference Levels (LDRLs),established according to the standardized approach proposed by the Radiation Protection 185 report (RP185). METHODS: Paediatric catheterization procedures conducted at the University-Hospital of Padua from September 2019 to December 2022 were stratified by body weight (BW) classes and procedure type. LDRLs were calculated for groups with at least 20 patients as the 75th percentile of Kerma-Area Product (PKA) and Air Kerma at reference point (Ka,r) values. Kruskal-Wallis test was applied to evaluate differences in the dose-related quantities among BW groups for a selected procedure and among procedures for the same BW class. Results were compared with recent literature. RESULTS: A total of 838 procedures were analysed. LDRL were provided for five therapeutic procedures. The 75th percentile of PKA and Ka,r increases with weight, regardless procedure type. PKA and Ka,r are generally statistically different between BW groups, for both diagnostic and therapeutic procedures, and between different procedures at fixed weight group. Angioplasty and Right Ventricular Outflow Tract treatments (PVR) showed exposure values approximately doubled then other procedures. PKA/(BW·FT) is not statistically different among procedures except for Atrial Septal Defect (ASD) closures. LDRL values from this study are generally lower than the published ones. CONCLUSIONS: The study stands out as one of the few that presents a considerable number of LDRLs for weight categories and procedure types with a sample size of at least 20 patients per group, in agreement with RP185. PKA shows strong correlation with the product BW·FT.

Asunto(s)

Cardiología , Humanos , Niño , Italia , Niveles de Referencia para Diagnóstico , Preescolar , Derivación y Consulta , Lactante , Adolescente , Dosis de Radiación , Femenino , Peso Corporal , Estándares de Referencia , Masculino

RESUMEN

This article is the second of a series of two articles. In the first article of the series, a new Kv distribution model and an experimental methodology to measure the Kv distribution were introduced. In this second part, the Kv distribution is integrated into a lyo-simulation tool, to more accurately predict the variability of the product temperature, primary drying time, total sublimation mass flow and Pirani signal. The Kv distribution is also integrated into the graphical design space. The impact of incorporating the Rp distribution is briefly discussed. The comparison of the simulation tool with actual product temperature monitoring, Pirani signal or overall sublimation flow shows very good agreement in the case studies presented. Overall, the lyo-simulation incorporating the Kv distribution is a very useful tool to support industrial development, i.e. process optimization, scale assessment, technology transfer, and troubleshooting of the lyophilization process.

Asunto(s)

Simulación por Computador , Liofilización , Temperatura , Liofilización/métodos , Tecnología Farmacéutica/métodos , Modelos Químicos

RESUMEN

This study compiles the information for the development of analytical methods for estimation of the Tizanidine HCl that will be helpful for further research work on this drug and its impurity. The present Literature survey provides information about the Analytical methods like UV,TLC,RP-HPLC,HPTLC,UHPLC and other methods have been reported for Tizanidine HCl drug individually and along with other drugs. The analysis of published data revealed that, there was only UV spectroscopic method (calibration curve metod) is reported for estimation of Tizanidine HCl fixed dose combination. Estimation of Tizanidine HCl by superlative RP-HPLC method i.e. Mobile phase- Acetonitrile: phosphate buffer (pH: 7.5) (50:50%v/v), Column C18 (250mm*4mm*5µm), Flow rate- 1.0 ml/min, Wavelength: 318 nm. Optimized HPLC condition was validated by assessing validation parameters and it meet the acceptance criteria set by ICH. It was showed method was linear and precise. The validated RP-HPLC-PDA method can be used for routine analysis of Tizanidine HCl in tablet.

Asunto(s)

Clonidina , Cromatografía Líquida de Alta Presión/métodos , Clonidina/análogos & derivados , Clonidina/análisis , Cromatografía de Fase Inversa/métodos

RESUMEN

Background/aim: Glioblastoma is one of the most aggressive tumours, resistant to all applied therapy regiments and prone to relapse. Median survival rates are therefore only expressed as months. STING agonists are immunomodulatory molecules that activate type I interferon expression, making them potentially useful in regulating the tumour microenvironment. Since PTEN serves as a critical phosphatase in activating interferon-regulating transcription factors and is frequently mutated in glioblastoma cells, this study aimed to investigate STING activation in glioblastoma cell lines, examining whether they harbour the PTEN protein or not.°. Materials and methods: T98G and U118MG glioblastoma cell lines were treated with the 2'3'-c-di-AM(PS)2(Rp,Rp) STING agonist together with or without the chemotherapeutic agent temozolomide. cGAS/STING pathway components were subsequently analysed using qRT-PCR, western blot, and ELISA methods. Results: Our results showed that PTEN-harbouring T98G cells responded well to STING activation, leading to increased temozolomide efficacy. In contrast, STING activation in U118MG cells did not affect the response to temozolomide. mRNA expression levels of STING, IRF3, NF-KB, and RELA genes were significantly increased at the combined treatment groups in T98G cell line. Conversely, combined treatment with STING agonist and temozolomide did not affect mRNA expression levels of cGAS/STING pathway genes in U118MG cells. Conclusion: Our data offers new evidence suggesting that STING agonists can effectively be used to increase temozolomide response in the presence of PTEN protein. Therefore, increased GBM therapy success rates can be achieved by employing the PTEN expression status as a predictive biomarker before treating patients with a chemotherapeutic agent in combination with STING agonist.

Asunto(s)

Glioblastoma , Proteínas de la Membrana , Fosfohidrolasa PTEN , Temozolomida , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Temozolomida/farmacología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Línea Celular Tumoral , Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Factor 3 Regulador del Interferón/metabolismo

RESUMEN

Physical exercise (PE) may be the single most important and accessible lifestyle habit throughout life, it inhibits the neuroinflammatory response and protects the brain against damage. As the innate cells in brain, microglia undergo morphological and functional changes to communicate with neurons protecting the neurons from injury. Herein, aiming at exploring the effects of PE on the communication between microglia-neuron during acute ischemic cerebral infarction, we carried out running wheel training before the conduction of transient middle cerebral artery occlusion (tMCAO) in C57BL/6 J and Cx3cr1-GFP mice. We found that microglial P2Y12 expression in the peri-infarct area was decreased, microglial dynamics and microglia-neuron communications were impaired, using in vivo two-photon imaging. PE up-regulated the microglial P2Y12 expression, increased the microglial dynamics, and promoted the contacts of microglia with neurons. As a result, PE inhibited neuronal Ca2+ overloads and protected against damage of the neuronal mitochondria in acute tMCAO. Mechanistically, PE increased the cannabinoid receptor 2 (CB2R) in microglia, promoted the phosphorylation of Nrf2 (NF-E2-related factor 2) at ser-344, increased the transcription factor level of Mafk, and up-regulated the level of P2Y12, whereby PE increased the levels of CB2R to promote microglia-neuron contacts to monitor and protect neuronal function.

RESUMEN

This study was conducted in nutrient-restricted pregnant Hu ewes to determine whether rumen-protected arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation affects fetal liver growth and development. From 35 d to 110 d of gestation, 32 Hu ewes were randomly divided into four groups: a control group (100% of the National Research Council (NRC) requirements), a nutrient-restricted group (50% of the NRC requirements), and two treatment groups (ARG and NCG, 50% of the NRC requirements, supplemented with 20 g/day RP-Arg or 5 g/day NCG, respectively). Fetal body weights, fetal liver growth performance, the capability of antioxidation, and the expression of the mRNA and proteins of apoptosis-related genes in the fetal liver were determined and analyzed at 110 d of gestation. The dry matter, water, fat, protein, and ash components of the fetal livers in the RG group were found to be lower than in the CG group, and these components were significantly higher in the NCG group than in the RG group (p < 0.05). A decrease in DNA, RNA, and protein concentrations and contents, as well as in protein/DNA ratios, was observed in the RG group in comparison to the CG group (p < 0.05). Compared with the RG group, the NCG group had higher concentrations of DNA, RNA, and protein, as well as higher protein/DNA ratios (p < 0.05). The RG group had lower concentrations of cholinesterase, nitric oxide, nitric oxide synthase, superoxide dismutase, alanine aminotransferase, and total protein than the CG group (p < 0.05). The RG group had higher levels of glutathione peroxidase, maleic dialdehyde, and aspartate aminotransferase than the CG group (p < 0.05). In the RG group, the mRNA and protein expression of p53 and Bax was significantly increased (p < 0.05) compared with the CG group, and the gene expression of FasL and Bcl-2, the ratio of Bcl-2 to Bax, and the protein expression of Bcl-2 in the RG group were lower (p < 0.05) than in the CG group. It appears that RP-Arg and NCG supplementation during pregnancy could influence fetal liver growth and development. A nutrition-based therapeutic intervention to alleviate reduced fetal growth can be developed based on this study, which has demonstrated that maternal undernutrition during pregnancy induces the maldevelopment of the fetal liver.

RESUMEN

Background: In recent years, despite several surgical techniques having been applied, the early incontinence rate after radical prostatectomy (RP) remains high. In this study, we reconstructed an internal urethral sphincter (IUS) with anterior bladder neck tube (ABNT) to improve early return of continence and find a more effective technique for early urinary incontinence after RP. Methods: In this study, 96 previous patients who did not receive an ABNT between October 2018 and May 2020 were compared as historical controls (the control group). A total of 210 consecutive patients underwent robotic or laparoscopic RP with ABNT between May 2020 and February 2023 (the ABNT group). The inclusion criteria included Eastern Cooperative Oncology Group (ECOG) score 0-1 and localized prostate cancer (clinical stages cT1-3, cN0, cM0). The exclusion criteria included patients with diabetes, neurologic diseases, previous pelvic operations, symptoms of urinary incontinence, prior radiation, focal therapy, or androgen deprivation therapy for prostate cancer. ABNT was reconducted with a U-shaped flap from the anterior wall of the bladder neck, and was then anastomosed with the urethra. In the control group, the bladder outlet was directly anastomosed with the urethra. Continence, as defined if 0 pads were used per day and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score ≤6, was assessed at 1, 4, 8, 12, and 24 weeks after catheter removal. At 2 weeks after catheter removal, urethral pressure profilometry (UPP) and upright urethrography were performed to evaluate the function of ABNT in the ABNT group. Results: More patients in the ABNT group were continent than those in the control group at 1 week (85.2% vs. 22.9%, P<0.001), 4 weeks (91.4% vs. 27.1%, P<0.001), 8 weeks (95.2% vs. 40.6%, P<0.001), 12 weeks (100% vs. 71.9%, P<0.001), and at 24 weeks (100% vs. 87.5%, P<0.001) after catheter removal. Stricture was presented in 5.2% and 2.1% (P=0.34) in the ABNT group and control group, respectively. UPP showed that a functional IUS was reconstructed with ABNT. Upright urethrography showed that the ABNT was filled with contrast medium in the urination period and with no contrast medium during the storage period and interruption of urination. Conclusions: The ABNT technique significantly improved early return of continence in comparison with the no ABNT technique, especially the immediate continence. The ABNT technique reconstructed the functional IUS with acceptable urethral stricture. The limitations of the present study include that the comparison was conducted retrospectively with a historical cohort and lack of randomization, and the single center setting. A prospective, randomized, and multicenter evaluation is expected.