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El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.
The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.
Subject(s)
Animals , Male , Mice , Diet/adverse effects , Exenatide/administration & dosage , Obesity/etiology , Obesity/metabolism , Oxidation-Reduction , Blotting, Western , Muscle, Skeletal/metabolism , Thermogenesis , Fatty Acids/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Uncoupling Protein 2 , Irinotecan , Injections, Intraperitoneal , Mice, Inbred C57BLABSTRACT
@#Abstract: Objective To report the clinical characteristics and genetic test results of two children with neurofibromatosis type 1 (NF1), and to provide reference for the comprehensive diagnosis-treatment and follow-up plans of NF1 patients based on the existing diagnosis and treatment progress of NF1. Methods Two children with NF1 admitted to the Department of Children's Medicine, Haikou people's Hospital in May and June 2022 were selected to analyze the clinical data of their clinical manifestations, laboratory examination, genetic test results, diagnosis and treatment and follow-up retrospectively. Results Two children had typical clinical manifestations, such as café-au-lait spots, axillary freckles, intraocular iris hamartoma. Venous blood was collected from case 1 and his parents for NF gene test, and a new mutation of c.4084C>T in the NF1 gene was found, and their parents did not have the pathogenic gene; the venous blood of the children in case 2 was tested for whole-exome gene analysis, and a heterozygous nonsense variant c.910C>T:p.R304 on the NF1 gene was found, , which was verified by Sanger sequencing to be inherited from his mother, his mother has café-au-lait spots and brain glioma, and has undergone surgery to remove the brain glioma, but has not undergone chemoradiotherapy or targeted therapy. No neurological malignancies were detected in either of the two children at follow-up until July 2022. Conclusions The clinical manifestations of NF1 are relatively typical, genetic testing is conducive to determine its classification, and regular follow-up review can help to detect and treat malignant tumors early, thus improving the patient's quality of life.
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RESUMEN Antecedentes. Lograr un método ideal que evalúe el potencial de crecimiento fetal es una aspiración incumplida en nuestra disciplina, e impone la necesidad de una evaluación individualizada, a través de nuevas herramientas y multiparámetros integrados. Objetivos. Evaluar la correlación y establecer valores de referencia del índice cefálico/abdominal/femoral (CAF) con la edad gestacional (EG) y el peso fetal estimado, para tipificar la evolución del crecimiento fetal como adecuado o no para la edad gestacional, y correlacionar con el peso del recién nacido a término. Pacientes y métodos. Se estudiaron 1 032 embarazos con embarazo simple y sin complicaciones, de 12 a 38 semanas de gestación, en el Centro Policlínico de Valencia, Venezuela, entre los años 2015 y 2017. Las medidas ecográficas y el peso fetal se estimaron a intervalos de 3 a 5 semanas. Los parámetros estudiados fueron circunferencia cefálica (CC), circunferencia abdominal (CA) y longitud del fémur (FL), integrados en la fórmula índice CAF = [(CC + CA) -FL]. Se aplicó el modelo de regresión cúbica y puntaje Z en 256 casos seguidos hasta el parto. Se establecieron tres grupos de CAF: a) CAF <50, b) CAF 50 a 57, y c) CAF ≥58, calculando la media ± desviación estándar de los pesos de los recién nacidos en cada grupo. Resultados. Según las semanas de gestación, el índice CAF reveló un R² = 0,96, p <0,05, mientras que para el peso fue R² = 0,92, p <0,05. En 256 casos seguidos hasta el parto, cuando el CAF tenía valor igual o superior a 58, el peso del recién nacido fue 3 361 ± 484 g, con diferencias estadísticamente significativas en relación al resto de grupos (prueba de student p <0,05). Conclusiones. El índice CAF es un método multiparméetrico que permite, a través de evaluaciones seriadas, determinar el potencial de crecimiento individual esperado y virtualmente también identificar sus desviaciones.
ABSTRACT Background: Achieving an ideal method to assess the potential for fetal growth is an unfulfilled aspiration in our discipline, and imposes the need for individualized evaluation using new tools and integrated multi-parameters. Objectives: To evaluate correlation and to establish cephalic/abdominal/femoral (CAF) index reference values with gestational age (GA) and estimated fetal weight, in order to classify fetal growth evolution as adequate or not adequate for gestational age, and correlation with weight of the newborn at term. Patients and methods: 1 032 simple and not complicated pregnancies 12 to 38 weeks of gestation were studied at the Polyclinic Center of Valencia, Venezuela, between 2015-2017. Ultrasound measurements and fetal weight were estimated at 3-5 weeks intervals. Studied parameters were head circumference (HC), abdominal circumference (AC) and femur length (FL), integrated in the CAF index = [(HC + AC) - FL] formula. The cubic regression model and Z-score were applied in 256 cases followed up to delivery. Three CAF groups were established: a) CAF <50, b) CAF 50-57, and c) CAF ≥58; the mean ± SD newborn weights were calculated in each group. Results: The CAF index revealed an R² = 0.96, p <0.05 for weeks of gestation, and R² = 0.92, p <0.05 for weight. In 256 cases followed up to delivery, when the CAF index was equal or greater than 58, the newborn weight was 3 361 ± 484 g, with statistically significant differences as compared to the other groups (student test p <0.05). Conclusions: The CAF index is a multiparametric method that allows to determine by serial evaluations the expected individual growth potential and virtually to identify deviations.
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O adenocarcinoma cervical in situ é uma doença rara, totalmente curável, diagnosticada predominantemente por meio de rastreamento cervicouterino seguido de biópsia guiada por colposcopia e/ou conização. O tratamento em pacientes que desejam preservar a fertilidade pode ser realizado num contexto ambulatorial; aquelas com paridade definida deverão ser abordadas em nível terciário.(AU)
Cervical adenocarcinoma in situ is a rare, fully curable disease diagnosed predominantly through cervical-uterine screening followed by colposcopy-guided biopsy and/or conization. Treatment in patients wishing to preserve fertility may be performed in an outpatient setting; those with defined parity should be approached at the tertiary level.(AU)
Subject(s)
Humans , Female , Primary Health Care , Secondary Care , Uterine Cervical Neoplasms , Adenocarcinoma in Situ , Squamous Intraepithelial Lesions of the Cervix , Cervix Uteri/physiopathology , ColposcopyABSTRACT
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
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We report the retinal and choroidal manifestations using multimodal imaging in a patient with Neurofibromatosis type 1 (NF-1). In this report, we describe the occurrence of a new retinal finding which we label as retinal caf�-au-lait macules. Also, we describe the superiority of multicolour imaging in comparison to colour fundus photography for identifying the retinal manifestations in NF-1.
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Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin (MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate (IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin-isonicotinamide (MYR-INM) and myricetin-caffeine (MYR-CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure. The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer (CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR-INM (1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.
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Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
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@#Cancer-associated fibroblasts (CAFs) are one of the major cellularcomponents in tumor microenvironment (TME), which play an important role in cancer progression. MicroRNAs (miRNAs) could participate in the process of CAFs, transformation and metabolism reprogramming, affect the stemness of CAFs, and regulate CAFs-mediated tumor cell proliferation, invasion and chemotherapy resistance; and studies have shown that miRNAs play an important role in CAFs formation and the regulation of CAFs on tumors. The miRNAs released by CAFs can be used as reference indicators for tumor diagnosis, prognosis and drug selection. Thus, exploring the role of miRNAs in the interaction between CAFs and tumor cells and underlining the mechanism, is of great significancefor understanding the occurrence and development of tumors, as well as providing novel strategy for cancer treatment. This review will summarize the role of miRNAs in the formation of CAFs and the regulation of CAFs on tumor cells.
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@# Objective: To investigate the effects of prostate cancer exosomes on the migration and invasion ability of stromal cells (WPMY-1), and to explore its mechanism. Methods: Exosomes in LNCaP-AI+F prostate cancer cell supernatant were isolated by ultracentrifugation and the typical structure of exosome was captured by electron microscope. The particle size distribution was analyzed by Zetaview, and Wb was used to identify the marker proteins and other proteins.After co-incubation of WPMY-1 cells and prostate cancer exosomes (40 µg/ml), laser confocal microscope was used to observe the uptake of PKH67-labeled exosomes by WPMY-1 cells; Transwell assay was used to detect the migration and invasion ability of WPMY-1 cells; qPCR was performed to detect the expression of three cancer-associated fibroblast (CAF)-related molecules (IL-8, PDGFB and MMP9) at mRNA level; and the phosphorylation of EGFR and ERK1/2 was analyzed by Wb. Results: Typical cup-shaped structure of exosomes was observed under electron microscope. The Zetaview results showed that the particle size distribution was concentrated at about 100 nm. The expression of exosome marker proteins CD63 andALIX further verified that the isolated particles were exosomes. Besides, EGFR, HER2 and SRC, which were related to the progression of prostate cancer, were also enriched in exosomes. After co-incubation, confocal microscope imaging showed a number of PKH67 labeled exosomes in recipient WPMY-1 cells. Transwell experiments showed that exosomes could significantly enhance the migration and invasion ability of WPMY-1 cells (all P<0.01). Compared with the control group, increased secretion of IL-8, PDGFB and MMP9 was observed after exosome treatment (40 µg/ml) (P<0.05 or P<0.01). Wb indicated that exosomes could promote the phosphorylation of EGFR and ERK1/2 of WPMY-1 cells (P<0.01). Conclusion: Prostate cancer cell exosomes could act on the stromal cell WPMY-1 to highly express multiple CAF-related molecules, promote the phosphorylation of EGFR and ERK1/2 and enhance the migration and invasion ability of WPMY-1 cells.
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Objective To identify the causes of nonspecific bands in the detection of a industry standard caf1 gene by polymerase chain reaction(PCR),and to propose a solution to this problem. Methods A total of 112 strains were selected for the experiment, including 40 strains of Yersinia pestis, 72 strains of non-Yersinia pestis;DNA was extracted,and caf1 gene was amplified by PCR;seven non-specific strips were recovered,purified and TA cloning and sequencing; the primer of the caf1 gene was redesigned and validated using all of the strains. Results Using the industry standard caf1 gene primer,DNAs of 40 Yersinia pestis and 72 non-Yersinia pestis were amplified by PCR, 58 non-Yersinia pestis could be amplified with non-specific bands, they were about 400, 500, 600, 700, 800, 900, 1 000 bp. By TA cloning and sequencing, the non-specific bands in the downstream of the industry standard caf1 primer and its reverse complement were amplified. Using the new designed caf1 primer to amplify, 72 non-Yersinia pestis strains showed no non-specific bands. Conclusion Non-specific bands has been amplified in the screening of Yersinia pestis using the primer of the industry standard caf1, and the new caf1 primer can effectively avoid this problem and improve the accuracy of detection.
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OBJECTIVE:To study the effects of caffeoylquinic acid derivative fractions (CADF) in Miao medicine Periploca forrestii on proliferation and secretion of inflammatory cytokines in tumor necrosis factor α(TNF-α)-induced human rheumatoid ar-thritis(RA)fibroblast-like synoviocytes MH7A,and explore its mechanism on anti-RA. METHODS:MH7A cells were divided in-to blank group,TNF-α model group,methotrexate group (positive control,20 mg/L) and CADF different mass concentrations groups(50,100,200,400 mg/L). Except for blank group,other groups received 50 μg/L of TNF-α to stimulate MH7A cells. Af-ter treated by suspension with TNF-α and related medicines for 24 h,the cell proliferation and contents of nitric oxide(NO),pros-taglandin E2 (PGE2),interleukin 1β(IL-1β),interleukin 6 (IL-6) in culture medium were detected. RESULTS:Compared with blank group,cell proliferation activity in TNF-αmodel group was significantly enhanced(P<0.01),contents of NO,PGE2,IL-1β, IL-6 in culture medium were significantly increased(P<0.01). Compared with TNF-α model group,cell proliferation in each ad-ministration group were significantly inhibited(P<0.05 or P<0.01),contents of NO,PGE2,IL-1β,IL-6 in culture medium weresignificantly decreased (P<0.01),showing certain dose-effect relationship with CADF. CONCLUSIONS:CADF can play the role in anti-RA by inhibiting the TNF-α-induced prolifera-tion of MH7A cells and reducing the secretion of inflammatory cytokines NO,PGE2,IL-1β,IL-6.
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OBJECTIVE:To establish a method for the simultaneous determination of paracetamol,amantadine hydrochloride, caffeine,chlorphenamine maleate in Compound paracetamol and amantadine hydrochloride tablet. METHODS:GC was performed on the column of HP-5 sillica capillary,temperature programmed,detector was FID detector,with the temperature of 300 ℃,car-rier gas was nitrogen gas,the flow rate is 1.5 mL/min,the split ratio was 20:1 and injection volume was 1μL. RESULTS:The lin-ear range was 156.0-4990.4 μg/mL for paracetamol,125.7-4023.2 μg/mL for amantadine hydrochloride,19.14-612.4 μg/mL for caffeine and 2.515-80.48 μg/mL for chlorphenamine maleate(all r=0.9999);the limits of quantification were 1.4,0.5,1.1,0.9 ng,limits of detection were 0.4,0.2,0.3,0.3 ng;RSDs of precision,stability and reproducibility tests were lower than 2.0%;re-coveries were 99.59%-101.77%(RSD=0.8%,n=9),99.56%-101.80%(RSD=0.7%,n=9),98.44%-100.83%(RSD=0.7%,n=9) and 100.05%-101.91%(RSD=0.6%,n=9),respectively. CONCLUSIONS:This method is simple,rapid,accurate and reli-able,and suitable for the simultaneous determination of paracetamol,amantadine hydrochloride,caffeine,chlorphenamine maleate in Compound paracetamol and amantadine hydrochloride tablet.
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OBJECTIVE:To study the effects of caffeoylquinic acid derivative fractions (CADF) in Miao medicine Periploca forrestii on proliferation and secretion of inflammatory cytokines in tumor necrosis factor α(TNF-α)-induced human rheumatoid ar-thritis(RA)fibroblast-like synoviocytes MH7A,and explore its mechanism on anti-RA. METHODS:MH7A cells were divided in-to blank group,TNF-α model group,methotrexate group (positive control,20 mg/L) and CADF different mass concentrations groups(50,100,200,400 mg/L). Except for blank group,other groups received 50 μg/L of TNF-α to stimulate MH7A cells. Af-ter treated by suspension with TNF-α and related medicines for 24 h,the cell proliferation and contents of nitric oxide(NO),pros-taglandin E2 (PGE2),interleukin 1β(IL-1β),interleukin 6 (IL-6) in culture medium were detected. RESULTS:Compared with blank group,cell proliferation activity in TNF-αmodel group was significantly enhanced(P<0.01),contents of NO,PGE2,IL-1β, IL-6 in culture medium were significantly increased(P<0.01). Compared with TNF-α model group,cell proliferation in each ad-ministration group were significantly inhibited(P<0.05 or P<0.01),contents of NO,PGE2,IL-1β,IL-6 in culture medium weresignificantly decreased (P<0.01),showing certain dose-effect relationship with CADF. CONCLUSIONS:CADF can play the role in anti-RA by inhibiting the TNF-α-induced prolifera-tion of MH7A cells and reducing the secretion of inflammatory cytokines NO,PGE2,IL-1β,IL-6.
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Background: The aim of the study is to assess the tumor response to neoadjuvant chemotherapy with cyclophosphamide, adriamycin, 5-fluorouracial (CAF regimen) in terms of decrease in breast tumor size (partial or complete clinically).To assess clinically the axillary lymph node status after neoadjuvant chemotherapy (conversion from palpable to nonpalpable). Methods: Thirty female patients of breast cancer were studied for down staging with two cycles of CAF regimen given at interval of 21 days. After 21 days of second cycle patient’s staging noted for effects. Results: Thirty female patients of breast cancer were studied. Maximum no. of patients between 31-40 years, mean age 46 years and median age 45 years, youngest patients 18 years, oldest patients 70 years, 22 patients responded to chemotherapy, out of 22, 1 (3.3%) showed a complete clinical response, 21 (70%) partial clinical response. Pre-menopausal 9/13 (69.2%) and post menopausal 13/17 (76.4%) showed clinical response, statistically not significant difference (df=1, x2=1.33, p>0.05). Change in tumor size 40.09±25.20 sq, cm mean size to 21.88±27.43 sq. cm after chemotherapy was highly significant change (t=6.242, p<0.001). Overall response to chemotherapy was 73.3%, in stage II-87.5%, stage IIIA-75% and stage IIIB-50%. The overall response to axillary lymph node was 56.6%, statistically highly significant (p<0.001). Main side effects nausea and vomiting (60%) and hair loss, 43.3%, but none necessitated stoppage of chemotherapy. As a consequence to primary chemotherapy, conservation surgery (lumpectomy with axillary clearance) could be done in 43.3% of patients.Conclusion: CAF Preoperative chemotherapy regime is a satisfactory modality of treatment for stage II and III breast cancer with positive response rate of 73.3%. The down staging thus obtained permits breast conservation surgery in 43.3% of patients. The chemotherapy regime is well accepted by patients.
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@#BACKGROUND:Airway foreign bodies (AFBs) is an interdisciplinary area between emergency medicine, pediatrics and otolaryngology. It is a life-threatening condition that is not infrequently seen; however, it is poorly covered in medical literature. Accidental aspiration of an element into airways is a widespread clinical scenario among children under 3 years, predominantly males. Moreover, it is the leading cause of infantile deaths and the fourth one among preschool children. DATA RESOURCES:A systemic search was conducted in July 2015 using PubMed/PubMed Central Database of The National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm. nih.gov/). A total of 1767 articles were identified and most of them were meta-analyses, systematic reviews, and case series. Those thoroughly discussing assessment and management of AFBs were retrieved. RESULTS:AFBs episodes may be either witnessed or missed. Presence of a witness for the inhalation is diagnostic. The later usually present with persistent active cough. A classical triad of paroxysmal cough, wheezing, and dyspnoea/decreased air entry was reported, though many presentations have inconsistent findings. Hence, diagnosis requires high index of clinical suspicion. Flexible fibro-optic bronchoscopy is the gold standard of diagnosis, whereas inhaled objects are best retrieved by rigid bronchoscopes. CONCLUSIONS:Close supervision of pediatrics is the hallmark of prevention. Caregivers should ensure a safe surrounding milieu, including the toys their offspring play with. Immediate complications result from direct obstruction or injury by the inhaled object. Alternatively, prolonged lodging traps air and induces inflammatory response causing atelectesis and pneumonia, respectively.
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@#Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing’s syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings is because of a molecular defect due to dominant activating mutations in the widely expressed signalling protein Gsα. These mutations arise sporadically, often early in development, prior to gastrulation and can distribute across many or few tissues.1,2 We present a case of a 3½ year-old-girl who presented simultaneously with precocious puberty and hypophosphatemic rickets, along with fibrous dysplasia and café au lait macules.
Subject(s)
Fibrous Dysplasia, Polyostotic , Puberty, Precocious , Rickets, HypophosphatemicABSTRACT
The process of malignancy emergence is associated with the acquisition of the capacity to invade other tissues. Several different biological processes have been described as involved in this process. Specifically, epithelial mesenchymal transition (EMT), a mechanism associated with embryogenesis and wound repair but also with mobility acquisition, is one of the concerned processes. In EMT an epithelial cell loses its epithelial characteristics, its junctions with neighbor cells and with the basal lamina and acquires mobility and mesenchymal characteristics. Also, factors of the tumor microenvironment have been described as involved. Tumor presence triggers a response in the surrounding tissue known as reactive stromal. It shows particular characteristics similar to those found in wound healing stroma: an increase of the fibroblast number and enhancing of the capillary density. The notable difference is the chronicity in the tumoral process. Of a high relevance seems to be the role of activated macrophages with a characteristic phenotype. Finally, cancer associated fibroblasts (CAF) are a type of cells found in tumors, developed from local tissue or possibly from bone marrow. CAF characteristically show a distinct morphology and secrete a high number of metalloproteases allowing tumoral cells advance through the tissue. Additionally, CAF have a direct effect on the survival of the epithelial cells. The three processes are interrelated and metastasis is probably caused by the effect of all of them and probably by other additional factors.
El desarrollo de malignidad está asociado con la adquisición de la capacidad de invadir otros tejidos. Varios procesos diferentes han sido asociados con la aparición de metástasis. Concretamente, la transición epitelio mesénquima (TEM), un mecanismo asociado con embriogénesis y reparación de heridas pero también con adquisición de movilidad, es uno de ellos. En la TEM, una célula epitelial pierde sus características epiteliales, sus uniones con las células vecinas y con la lámina basal y adquiere movilidad y características mesenquemáticas. También han sido asociados factores del microambiente del tumor. La presencia del tumor produce una respuesta en el tejido que lo rodea descrito como estroma reactivo. Sus características son similares a las del estroma de las heridas en proceso de curación: un incremento del número de fibroblastos y un aumento de la densidad de capilares. La gran diferencia es la cronicidad del proceso tumoral. De gran relevancia es el papel de los macrófagos activados que muestran un fenotipo característico. Finalmente, los fibroblastos asociados a cáncer (FAC) son un tipo de células encontradas en tumores, que se desarrollan a partir del tejido local o quizá de la médula ósea. Los FAC, de modo característico muestran una morfología diferente y secretan una gran cantidad de metaloproteasas permitiendo a la célula tumoral avanzar a través del tejido. Además, los FAC ejercen un efecto directo sobre la supervivencia de las células epiteliales. Los tres procesos están interrelacionados y la metástasis es causada probablemente por el efecto de todos ellos y probablemente por otros factores adicionales.
Subject(s)
Humans , Epithelial Cells/pathology , Cancer-Associated Fibroblasts/pathology , Neoplasm Metastasis/pathology , Epithelial-Mesenchymal Transition , Neoplasm Invasiveness , Neoplasms/pathologyABSTRACT
O café e a cafeína são dois potenciais agentes preventivos contra o desenvolvimento ou avanço dos processos de fibrose/cirrose e carcinogênese hepática em humanos, entretanto suas ações são controversas e muitas vezes inconclusivas. Devido a isto, o objetivo deste trabalho foi verificar a ação do café ou da cafeína isolada no fígado de ratos Wistar tratados com tioacetamida (TAA) ou tetracloreto de carbono (CCl4). Para tanto, os dados experimentais foram distribuídos em dois artigos. No primeiro artigo, foram avaliados os efeitos do café convencional, descafeinado e da cafeína isolada na hepatotoxicidade induzida pela TAA em ratos Wistar. Para tanto, 60 os animais foram divididos em 5 grupos experimentais: G1 (controle negativo), G2 (controle positivo tratado com TAA 200 mg/Kg i.p.), G3 (TAA + café convencional), G4 (TAA + café descafeinado) e G5 (TAA + cafeína a 0,1%). Ao final de 8 semanas de tratamento os ratos foram eutanasiados para coleta do sangue (análises séricas) e do fígado (análises histológicas, histoquímicas e moleculares). De maneira geral os animais tratados com café/cafeína (G3-G5) apresentaram níveis da enzima alanina aminotransferase (ALT), área ocupada por colágenos I e III e expressão da proteína TGF-beta1 menores que o grupo controle positivo (G2). Adicionalmente, os grupos G3 e G5 apresentaram menor número de núcleos PCNA positivos em fase S do que o grupo G2. O grupo G3 também apresentou menor número de focos GST-P positivos que o grupo G2. Ademais, os grupos G4 e G5 apresentaram as maiores atividades de MMP-2 ativa. Em conclusão, tanto o café convencional como o descafeinado como a cafeína a 0,1% apresentaram efeitos benéficos, mostrando que os outros componentes do café, mesmo sem a cafeína, ou que somente a cafeína são capazes de reduzir a hepatotoxicidade no fígado de ratos Wistar tratados com TAA..(...)
Consumption of coffee beverages reduces the incidence of liver disease. However, whether these beneficial effects on human health are due to caffeine or other specific components in the beverage remains controversial. There, the present study aimed to study evaluated the protective effects of coffee beverages or caffeine on liver toxicity induced by repeated administration of the hepatotoxicant thioacetamide (TAA) in male Wistar rats. Animals were randomized into five groups: untreated controls (G1) TAA only (G2, 200 mg/Kg b.w. twice a week for 8 weeks, i.p.), TAA+conventional coffee (G3), TAA+decaffeinated coffee (G4) and TAA+caffeine (G5, 0.1% in the drinking water). At the end of 8 weeks, the animals were euthanized and blood and liver samples were collected. Serum ALT levels were lower in animals that received coffee and caffeine (p < 0.001). In addition, liver oxidized glutathione (p < 0.05), fibrosis/inflammation score (p < 0.001) and TGF-beta expression (p ¡Ü 0.001) was reduced in these groups when compared to TAA-only rats. Moreover, conventional coffee and caffeine reduced PCNA S-phase index (p < 0.001) but only conventional coffee reduced cleaved caspase-3 index (p < 0.001) and active metalloproteinase 2 (p ¡Ü 0.004) in the liver from TAA-treated animals.(...)
Subject(s)
Animals , Male , Rats , Caffeine/adverse effects , Liver Neoplasms/etiology , Rats, WistarABSTRACT
Objective To get recombinant F1 antigen (rF1) and to construct the detection dipstick of plague antibody. Methods The cafl gene removing the signal peptide coding sequence was cloned into plasmid pET32a ( +) by double-digested sites of BamHI and Not I. Recombinant plasmid caf1-pET32a(+) was transformed into BL21 (DE3) and the rFl was expressed. Expression products were purified by affinity chromatography. Dual detection dipstick of plague antibody was constructed with purified rF1 and natural F1, and evaluated with 528 human serum samples of Zhejiang province. Results The fusion protein rF1 of 35.5 KD was expressed by BL21 strains containing caf1-pET32a( + ). The sensitivity of rF1 showed equivalent to or higher than the natural Fl antigen in detecting plague antibody. It seemed that there was a better consistency of 97.9% (k= 0.466) when 528 human sera was detected by rF1 and natural F1. Conclusion We successfully extracted the rF1 with good immunological activity that might be used to detecting Yersinia pestis.