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1.
Adv Physiol Educ ; 44(3): 453-458, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32795125

RESUMEN

Traditional oral examination (TOE) is criticized for the shortage of objectivity, standardization, and reliability. These perceived limitations can be mitigated by the introduction of structured oral examination (SOE). There is little evidence of the implementation of SOE in physiology laboratory courses. The purpose of this study was to investigate the effect of SOE in laboratory-based learning sessions. Second-year medical students (n = 114) attended a 16-wk physiology laboratory course. They were initially assessed by TOE in the middle of the academic term. The students' perspectives on this assessment were measured by a modified three-point Likert-type scale questionnaire. Following this, faculty members prepared topics for SOE; nine topics were included from each laboratory course. The correct answers and scoring criteria were discussed among the faculty before the SOE event. One week after the last laboratory course, SOE was carried out for each student. As with the TOE process, student feedback was collected via a modified three-point Likert-type scale questionnaire. The mean laboratory homework score from the first four and last four laboratory courses was also calculated. Paper exams were also conducted after TOE and SOE. The results show that SOE is more acceptable to students than TOE. Significant differences (P < 0.05) were observed in terms of uniformity of questions asked, syllabus coverage, and anxiety levels. In addition, SOE improved students' performance in the laboratory course explored here. We contend that SOE shows promise as an effective assessment tool in laboratory-based physiology learning sessions.


Asunto(s)
Educación de Pregrado en Medicina , Fisiología , Estudiantes de Medicina , Diagnóstico Bucal , Evaluación Educacional , Humanos , Laboratorios , Fisiología/educación , Reproducibilidad de los Resultados
2.
BMC Genomics ; 19(1): 408, 2018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29843592

RESUMEN

BACKGROUND: Small RNAs are critical components in regulating various cellular pathways. These molecules may be tissue-associated or circulating in bodily fluids and have been shown to associate with different tumors. Next generation sequencing (NGS) on small RNAs is a powerful tool for profiling and discovery of microRNAs (miRNAs). RESULTS: In this study, we isolated total RNA from various bodily fluids: blood, leukocytes, serum, plasma, saliva, cell-free saliva, urine and cell-free urine. Next, we used Illumina's NGS platform and intensive bioinformatics analysis to investigate the distribution and signature of small RNAs in the various fluids. Successful NGS was accomplished despite the variations in RNA concentrations among the different fluids. Among the fluids studied, blood and plasma were found to be the most promising fluids for small RNA profiling as well as novel miRNA prediction. Saliva and urine yielded lower numbers of identifiable molecules and therefore were less reliable in small RNA profiling and less useful in predicting novel molecules. In addition, all fluids shared many molecules, including 139 miRNAs, the most abundant tRNAs, and the most abundant piwi-interacting RNAs (piRNAs). Fluids of similar origin (blood, urine or saliva) displayed closer clustering, while each fluid still retains its own characteristic signature based on its unique molecules and its levels of the common molecules. Donor urine samples showed sex-dependent differential clustering, which may prove useful for future studies. CONCLUSIONS: This study shows the successful clustering and unique signatures of bodily fluids based on their miRNA, tRNA and piRNA content. With this information, cohorts may be differentiated based on multiple molecules from each small RNA class by a multidimensional assessment of the overall molecular signature.


Asunto(s)
Líquidos Corporales/metabolismo , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Pequeño no Traducido/genética , Análisis de Secuencia de ARN , Adulto , Femenino , Humanos , Masculino , Adulto Joven
3.
Tumour Biol ; 35(12): 11855-60, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25230785

RESUMEN

Genital human papillomavirus (HPV) is associated with the development of cutaneous malignant tumors, and differences in HPV subtypes are found in several cancers by histology. NF-κB is persistently activated in most cancers and confers a survival advantage to cancer cells, while A20 is a critical negative regulator of NF-κB and is an important tumor suppressor inactivated in B cell lymphomas. This study was undertaken to identify HPV types in cutaneous squamous cell carcinoma (SCC) as well as to determine whether the crosstalk of A20/NF-κB was involved in HPV-induced SCC. Overall, HPV positivity was observed to be 66.2 %, with HPV16 being most common followed by infection with HPV18. Out of 43 HPV-positive samples, 35 samples were positive for one or more high-risk HPV (HR-HPV) types, suggesting a high association of SCC with HR-HPV infection, while only five HPV infections were detected in 21 normal skin samples and low-risk HPV (LR-HPV) infection was the most common. Both A20 and NF-κB were overexpressed in HPV-positive SCC samples (56 vs 87.4 %) and were closely correlated with TNM stage and lymph node transfer, respectively. More interestingly, the expression of A20 and NF-κB was much higher in HR-HPV samples than in LR-HPV samples. These results suggest that the crosstalk of A20 and NF-κB may contribute to HR-HPV-associated tumor growth and metastasis of SCC and may be a novel therapeutic target for SCC in the future.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/metabolismo , Proteínas de Unión al ADN/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , FN-kappa B/metabolismo , Proteínas Nucleares/metabolismo , Infecciones por Papillomavirus/complicaciones , Adulto , Anciano , Alphapapillomavirus/genética , Carcinoma de Células Escamosas/patología , Femenino , Genotipo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Tipificación Molecular , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Infecciones por Papillomavirus/virología , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
4.
Appl Biochem Biotechnol ; 196(1): 261-274, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37119504

RESUMEN

Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold. The present study has used TOA2, while biodistribution analysis was performed in human lung carcinoma A549-induced tumor-bearing nude mice model. Intratumoral injection was applied onto tumor-bearing mice with the adenovirus (3×1010 VP per mouse). Mice were sacrificed at the end of the experiment and the organs were dissected. Biodistribution analysis was done with complete hexon gene detection in each organ using quantitative real-time polymerase chain reaction (qRT-PCR). The biodistribution and concentration profiles showed that the TOA2 is well distributed in the entire tumor tissue. After dose 3 at day 11, the concentration of the virus has increased in the tumor tissue from 2240.54 (± 01.69) copies/100 ng genome to 13,120.28 (± 88.21) copies/100 ng genome on the 18th day, which eventually approached 336.45 (± 23.41) copies/100ng genome on the day 36. On the contrary, the concentration of the same decreased in the order of the liver, kidney, spleen, lung, and heart over time but no distributional traces in gonads. But the concentration found decreased dramatically in blood and other organs, while at the end of the experiment no detectable distribution was seen besides tumor tissue. The study confirms that adenovirus-based tumor therapy using conditionally replicating competent oncolytic TOA2 exhibited great efficiency with no toxicity at all.


Asunto(s)
Carcinoma , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Animales , Ratones , Viroterapia Oncolítica/métodos , Ratones Desnudos , Distribución Tisular , Adenoviridae/genética , Vectores Genéticos/genética , Carcinoma/genética , Pulmón , Genes Relacionados con las Neoplasias , Línea Celular Tumoral , Virus Oncolíticos/genética , Replicación Viral
5.
Biomedicines ; 11(4)2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37189782

RESUMEN

Integral membrane proteins, known as Transient Receptor Potential (TRP) channels, are cellular sensors for various physical and chemical stimuli in the nervous system, respiratory airways, colon, pancreas, bladder, skin, cardiovascular system, and eyes. TRP channels with nine subfamilies are classified by sequence similarity, resulting in this superfamily's tremendous physiological functional diversity. Pancreatic Ductal Adenocarcinoma (PDAC) is the most common and aggressive form of pancreatic cancer. Moreover, the development of effective treatment methods for pancreatic cancer has been hindered by the lack of understanding of the pathogenesis, partly due to the difficulty in studying human tissue samples. However, scientific research on this topic has witnessed steady development in the past few years in understanding the molecular mechanisms that underlie TRP channel disturbance. This brief review summarizes current knowledge of the molecular role of TRP channels in the development and progression of pancreatic ductal carcinoma to identify potential therapeutic interventions.

6.
Life (Basel) ; 12(6)2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35743934

RESUMEN

Trauma and bone loss from infections, tumors, and congenital diseases make bone repair and regeneration the greatest challenges in orthopedic, craniofacial, and plastic surgeries. The shortage of donors, intrinsic limitations, and complications in transplantation have led to more focus and interest in regenerative medicine. Structures that closely mimic bone tissue can be produced by this unique technology. The steady development of three-dimensional (3D)-printed bone tissue engineering scaffold therapy has played an important role in achieving the desired goal. Bioceramic scaffolds are widely studied and appear to be the most promising solution. In addition, 3D printing technology can simulate mechanical and biological surface properties and print with high precision complex internal and external structures to match their functional properties. Inkjet, extrusion, and light-based 3D printing are among the rapidly advancing bone bioprinting technologies. Furthermore, stem cell therapy has recently shown an important role in this field, although large tissue defects are difficult to fill by injection alone. The combination of 3D-printed bone tissue engineering scaffolds with stem cells has shown very promising results. Therefore, biocompatible artificial tissue engineering with living cells is the key element required for clinical applications where there is a high demand for bone defect repair. Furthermore, the emergence of various advanced manufacturing technologies has made the form of biomaterials and their functions, composition, and structure more diversified, and manifold. The importance of this article lies in that it aims to briefly review the main principles and characteristics of the currently available methods in orthopedic bioprinting technology to prepare bioceramic scaffolds, and finally discuss the challenges and prospects for applications in this promising and vital field.

7.
Artículo en Inglés | MEDLINE | ID: mdl-35722136

RESUMEN

The pomegranate flower is an ancient herb in traditional Chinese medicine with multiple properties. Recent studies have shown that pomegranate flower extract is beneficial, especially for hyperglycemia. In this experiment, we investigated the diastolic effect of pomegranate flower polyphenol (PFP) extract on the isolated thoracic aorta of rats in both the absence and presence of high glucose levels. Isotonic contractile forces were recorded from aortic rings (about 3 mm in length) from rats using the BL-420F Biological Function Test System. Tissues were precontracted with 60 mM KCl to obtain maximum tension under 1.0 g load for 1 hour before the balance was achieved, and the fluid was changed every 15 minutes. PFP (700 mg/L-900 mg/L) showed a concentration-dependent relaxant effect on the aortic rings; vasodilation in the endothelium-intact was significantly higher than that in the de-endothelialized segments (P < 0.01). The endothelium-dependent vasorelaxant effect of PFP was partially attenuated by K+ channel blockers, tetraethylammonium (TEA), glibenclamide (Glib), and BaCl2, as well as L-NAME (eNOS inhibitor) on the denuded endothelium artery ring. Concentration-dependent inhibition of PFP on releasing intracellular Ca2+ in the Ca2+-free solution and vasoconstriction of CaCl2 in Ca2+-free buffer plus K+ (60 mM) was observed. In addition, PFP (0.1-10 mg/L) showed significant inhibition of acetylcholine-induced endothelial-dependent relaxation in the aorta of rats in the presence of high glucose (44 mmol/L). Nevertheless, the vasodilating effect of PFP was inhibited by atropine and L-NAME. The results indicated that PFP-induced vasodilation was most likely related to the antioxidant effects through enhanced NO synthesis, as well as the blocking of K+ channels and inhibition of extracellular Ca2+ entry. In conclusion, these observations showed that PFP ameliorates vasodilation in hyperglycemic rats. Hence, our results suggest that PFP supplementation may be beneficial for hypertensive patients with diabetes.

8.
Biomed Res Int ; 2021: 8823222, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33681381

RESUMEN

Nutraceuticals have taken on considerable significance due to their supposed safety and possible nutritional and medicinal effects. Pharmaceutical and dietary companies are conscious of monetary success, which benefits healthier consumers and the altering trends that result in these heart-oriented value-added products being proliferated. Numerous nutraceuticals are claimed to have multiple therapeutic benefits despite advantages, and unwanted effects encompass a lack of substantial evidence. Several common nutraceuticals involve glucosamine, omega-3, Echinacea, cod liver oil, folic acid, ginseng, orange juice supplemented with calcium, and green tea. This review is dedicated to improving the understanding of nutrients based on specific illness indications. It was reported that functional foods contain physiologically active components that confer various health benefits. Studies have shown that some foods and dietary patterns play a major role in the primary prevention of many ailment conditions that lead to putative functional foods being identified. Research and studies are needed to support the possible health benefits of different functional foods that have not yet been clinically validated for the relationships between diet and health. The term "functional foods" may additionally involve health/functional health foods, foods enriched with vitamins/minerals, nutritional improvements, or even conventional medicines.


Asunto(s)
Productos Lácteos , Suplementos Dietéticos , Alimentos Funcionales , Humanos
9.
Sci Rep ; 11(1): 4283, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608623

RESUMEN

Nowadays, artificial bone materials have been widely applied in the filling of non-weight bearing bone defects, but scarcely ever in weight-bearing bone defects. This study aims to develop an artificial bone with excellent mechanical properties and good osteogenic capability. Firstly, the collagen-thermosensitive hydrogel-calcium phosphate (CTC) composites were prepared as follows: dissolving thermosensitive hydrogel at 4 °C, then mixing with type I collagen as well as tricalcium phosphate (CaP) powder, and moulding the composites at 37 °C. Next, the CTC composites were subjected to evaluate for their chemical composition, micro morphology, pore size, Shore durometer, porosity and water absorption ability. Following this, the CTC composites were implanted into the muscle of mice while the 70% hydroxyapatite/30% ß-tricalcium phosphate (HA/TCP) biomaterials were set as the control group; 8 weeks later, the osteoinductive abilities of biomaterials were detected by histological staining. Finally, the CTC and HA/TCP biomaterials were used to fill the large segments of tibia defects in mice. The bone repairing and load-bearing abilities of materials were evaluated by histological staining, X-ray and micro-CT at week 8. Both the CTC and HA/TCP biomaterials could induce ectopic bone formation in mice; however, the CTC composites tended to produce larger areas of bone and bone marrow tissues than HA/TCP. Simultaneously, bone-repairing experiments showed that HA/TCP biomaterials were easily crushed or pushed out by new bone growth as the material has a poor hardness. In comparison, the CTC composites could be replaced gradually by newly formed bone and repair larger segments of bone defects. The CTC composites trialled in this study have better mechanical properties, osteoinductivity and weight-bearing capacity than HA/TCP. The CTC composites provide an experimental foundation for the synthesis of artificial bone and a new option for orthopedic patients.


Asunto(s)
Materiales Biocompatibles , Regeneración Ósea , Sustitutos de Huesos , Fosfatos de Calcio , Soporte de Peso , Animales , Sustitutos de Huesos/química , Fosfatos de Calcio/química , Fenómenos Químicos , Hidrogeles/química , Imagenología Tridimensional , Inmunohistoquímica , Ensayo de Materiales , Ratones , Modelos Animales , Prótesis e Implantes , Análisis Espectral , Microtomografía por Rayos X
10.
Biomed Res Int ; 2020: 6030581, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32802859

RESUMEN

This study aims at exploring the clinical efficacy and sonographic changes of photodynamic therapy (PDT) using Hematoporphyrin Monomethyl Ether (HMME) for the treatment of port-wine stains (PWS). Forty-five patients with PWS were recruited between March 2017 and June 2018 from the Department of Dermatology of The Third Affiliated Hospital of Soochow University. Five cases were of the pink type, thirty-nine cases were of the purple-red type, and one case was of the thickened type. All patients received three treatment sessions of PDT. After covering normal skin outside the treated area, patients received an intravenous injection of 5 mg/kg HMME within 20 minutes. The affected areas were exposed to a 532 nm LED light and were kept vertically at a distance of 10 cm. The irradiation energy density was set between 80 and 110 J/cm2 in 15-minute sessions. Intermittent power density adjustment was performed at a rate of 5 mW/cm2, and the treatment was withheld when the endpoint reaction appeared. Three follow-ups were performed before and after treatment, respectively, and the efficacy, thickness, and density of skin before and after treatment were evaluated with high-frequency ultrasound. The overall efficacy rate was 97.78% in forty-five cases after treatment for three sessions. Efficacy was related to age (P = 0.029) and lesion severity (P < 0.001). There were significant differences in the efficacy between the groups of <18 years old, 18-29 years old, and >29 years old (P = 0.029). A marked decrease in the numbers of distorted enlarged blood vessels per unit of the lesion was observed under high-frequency ultrasound. There were significant differences in skin thickness and skin density before and after treatment (F = 14.528, 5.428, P < 0.001). The swelling was reported to varying degrees in the treated areas in 23 patients with cheek lesion and in 6 frontal lesions. Hyperpigmentation after inflammation was observed in four patients that faded spontaneously after two months. In conclusion, photodynamic therapy for the treatment of PWS using HMME is effective and safe with few adverse reactions. Moreover, monitoring the changes in skin thickness and density of lesion tissue using high-frequency ultrasound can objectively evaluate the clinical efficacy of HMME photodynamic therapy and provide the basis for the formulation of individualized photodynamic therapy.


Asunto(s)
Hematoporfirinas/administración & dosificación , Fotoquimioterapia , Fármacos Fotosensibilizantes/administración & dosificación , Mancha Vino de Oporto , Adolescente , Adulto , Femenino , Humanos , Masculino , Mancha Vino de Oporto/diagnóstico por imagen , Mancha Vino de Oporto/tratamiento farmacológico , Mancha Vino de Oporto/patología , Ultrasonografía
11.
Metabolites ; 10(3)2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-32151083

RESUMEN

To investigate the osteoinductive mechanism triggered by hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) biomaterials in mice which keep exercising. Methods: The HA/ß-TCP biomaterials were implanted in the muscle of bilateral thighs (non-osseous sites) of eighty Balb/C mice. All animals were then randomly divided into 4 groups (n = 20). In group 1 (negative control group), the mice were fed routinely. In group 2 (running group), all mice were put on a treadmill which was set to a 60-degree incline. The mice ran 20 min thrice each day. A 5-minute break was included in the routine from day three onwards. In group 3 (weight-bearing group), all mice underwent weight-bearing running. The mice in this group performed the same routine as group 2 while carrying 5 g rubber weights. In group 4 (positive control group), dexamethasone was injected in the implanted sites of the biomaterials from the day of the operation. All mice were injected once per week and received a total of 8 injections. One and eight weeks after surgery, the blood serum was collected to detect inflammatory and immunological factors by ELISA. In addition to this, biomaterial specimens were obtained to observe inflammatory and osteogenic levels via histological staining and to facilitate analysis of the osteogenic mechanism by Western Blot. Results: The inflammation indexes caused by surgery were alleviated through running or weight-bearing running: The tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly reduced in groups 2 and 3 at week 8. Exercise also enhanced the secretion of interferon-γ (IFN-γ) in mice; this can strengthen their immunity. The new bone tissues were observed in all groups; however, the area percentage of new bone tissues and the number of osteoblasts were highest in the weight-bearing group. Furthermore, the key proteins of wingless/integrated (Wnt) signaling pathway, Wnt1, Wnt3a, and ß-catenin, were up-regulated during osteoinduction. This up-regulation activated runt-related transcription factor-2 (Runx2), increased the expression of osteopontin (OPN) and osteocalcin (OCN). Conclusion: Weight-bearing exercise can promote the bone and bone marrow formation through the Wnt signaling pathway: Observations documented here suggest that the proper exercise is beneficial to the recovery of bone damage.

12.
Perm J ; 232019.
Artículo en Inglés | MEDLINE | ID: mdl-31167708

RESUMEN

Patients often hand their physicians disability forms, and physicians too often struggle to complete them. Many physicians lack the training to complete these forms. This article aims to provide a clear understanding of impairment, limitations, restrictions, and disability. It explains how physicians can use skills they already possess to appropriately assess limitations, restrictions, and functional capacity, and it explains why accurate determinations are a vital part of good patient care.


Asunto(s)
Evaluación de la Discapacidad , Personas con Discapacidad , Reinserción al Trabajo , Evaluación de Capacidad de Trabajo , Competencia Clínica , Educación Médica , Indicadores de Salud , Humanos , Estados Unidos
13.
Biochem Pharmacol ; 153: 196-204, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29458047

RESUMEN

Methadone is a synthetic, long-acting opioid with a single chiral center forming two enantiomers, (R)-methadone and (S)-methadone, each having specific pharmacological actions. Concentrations of (R)- and (S)-methadone above therapeutic levels have the ability to cause serious, life-threatening, and fatal side effects. This toxicity can be due in part to the pharmacogenetics of an individual, which influences the pharmacokinetic and pharmacodynamic properties of the drug. Methadone is primarily metabolized in the liver by cytochrome P450 (CYP) enzymes, predominately by CYP2B6, followed by CYP3A4, 2C19, 2D6, and to a lesser extent, CYP2C18, 3A7, 2C8, 2C9, 3A5, and 1A2. Single nucleotide polymorphisms (SNPs) located within CYPs have the potential to play an important role in altering methadone metabolism and pharmacodynamics. Several SNPs in the CYP2B6, 3A4, 2C19, 2D6, and 3A5 genes result in increases in methadone plasma concentrations, decreased N-demethylation, and decreased methadone clearance. In particular, carriers of CYP2B6*6/*6 may have a greater risk for detrimental adverse effects, as methadone metabolism and clearance are diminished in these individuals. CYP2B6*4, on the other hand, has been observed to decrease plasma concentrations of methadone due to increased methadone clearance. The involvement, contribution, and understanding the role of SNPs in CYP2B6, and other CYP genes, in methadone metabolism can improve the therapeutic uses of methadone in patient outcome and the development of personalized medicine.


Asunto(s)
Analgésicos Opioides/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Metadona/metabolismo , Farmacogenética/tendencias , Polimorfismo de Nucleótido Simple/genética , Analgésicos Opioides/uso terapéutico , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/metabolismo , Farmacogenética/métodos
14.
J Anal Toxicol ; 41(4): 325-333, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28184434

RESUMEN

Cytochrome P450 (CYP) enzyme 2B6 plays a significant role in the stereo-selective metabolism of (S)-methadone to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine, an inactive methadone metabolite. Elevated (S)-methadone can cause cardiotoxicity by prolonging the QT interval of the heart's electrical cycle. Large inter-individual variability of methadone pharmacokinetics causes discordance in the relationship between dose, plasma concentrations and side effects. The purpose of this study was to determine if one or more single nucleotide polymorphisms (SNPs) located within the CYP2B6 gene contributes to a poor metabolizer phenotype for methadone in these fatal cases. The genetic analysis was conducted on 125 Caucasian methadone-only fatalities obtained from the West Virginia and Kentucky Offices of the Chief Medical Examiner. The frequency of eight exonic and intronic SNPs (rs2279344, rs3211371, rs3745274, rs4803419, rs8192709, rs8192719, rs12721655 and rs35979566) was determined. The frequencies of SNPs rs3745274 (*9, c516G > T, Q172H), and rs8192719 (21563 C > T) were enhanced in the methadone-only group. Higher blood methadone concentrations were observed in individuals who were genotyped homozygous for SNP rs3211371 (*5, c1459C > T, R487C). These results indicate that these three CYP2B6 SNPs are associated with methadone fatalities.


Asunto(s)
Analgésicos Opioides/sangre , Citocromo P-450 CYP2B6/genética , Sobredosis de Droga/genética , Metadona/sangre , Trastornos Relacionados con Opioides/genética , Citocromo P-450 CYP2B6/metabolismo , Sobredosis de Droga/metabolismo , Sobredosis de Droga/mortalidad , Humanos , Trastornos Relacionados con Opioides/metabolismo , Trastornos Relacionados con Opioides/mortalidad , Polimorfismo de Nucleótido Simple
15.
J Cancer ; 5(3): 182-91, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24563673

RESUMEN

MicroRNAs (miRNAs) are a class of short (~22nt), single stranded RNA molecules that function as post-transcriptional regulators of gene expression. MiRNAs can regulate a variety of important biological pathways, including: cellular proliferation, differentiation and apoptosis. Profiling of miRNA expression patterns was shown to be more useful than the equivalent mRNA profiles for characterizing poorly differentiated tumours. As such, miRNA expression "signatures" are expected to offer serious potential for diagnosing and prognosing cancers of any provenance. The aim of this study was to investigate the potential of using deregulation of urinary miRNAs in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the miRNA signatures specific for PCa, miRNA expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using whole genome expression profiling. Differential expression of two individual miRNAs between healthy males and BPH patients was detected and found to possibly target genes related to PCa development and progression. The sensitivity and specificity of miR-1825 for detecting PCa among BPH individuals was found to be 60% and 69%, respectively. Whereas, the sensitivity and specificity of miR-484 were 80% and 19%, respectively. Additionally, the sensitivity and specificity for miR-1825/484 in tandem were 45% and 75%, respectively. The proposed PCa miRNA signatures may therefore be of great value for the accurate diagnosis of PCa and BPH. This exploratory study has identified several possible targets that merit further investigation towards the development and validation of diagnostically useful, non-invasive, urine-based tests that might not only help diagnose PCa but also possibly help differentiate it from BPH.

16.
J Cancer ; 5(2): 103-14, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24494028

RESUMEN

Globally, Prostate cancer (PCa) is the most frequently occurring non-cutaneous cancer, and is the second highest cause of cancer mortality in men. Serum prostate specific antigen (PSA) has been the standard in PCa screening since its approval by the American Food & Drug Administration (FDA) in 1994. Currently, PSA is used as an indicator for PCa - patients with a serum PSA level above 4ng/mL will often undergo prostate biopsy to confirm cancer. Unfortunately fewer than ~30% of these men will biopsy positive for cancer, meaning that the majority of men undergo invasive biopsy with little benefit. Despite PSA's notoriously poor specificity (33%), there is still a significant lack of credible alternatives. Therefore an ideal biomarker that can specifically detect PCa at an early stage is urgently required. The aim of this study was to investigate the potential of using deregulation of urinary proteins in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the protein signatures specific for PCa, protein expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using LC-MS/MS. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant the down-regulation of Fibronectin and TP53INP2 was a characteristic event among PCa patients. Fibronectin mRNA down-regulation, was identified as offering improved specificity (50%) over PSA, albeit with a slightly lower although still acceptable sensitivity (75%) for detecting PCa. As for TP53INP2 on the other hand, its down-regulation was moderately sensitive (75%), identifying many patients with PCa, but was entirely non-specific (7%), designating many of the benign samples as malignant and being unable to accurately identify more than one negative.

17.
Forensic Sci Int Genet ; 6(1): 31-40, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21324769

RESUMEN

The ability to properly collect, analyze and preserve biological stains is important to preserving the integrity of forensic evidence. Stabilization of intact biological evidence in cells and the DNA extracts from them is particularly important since testing is generally not performed immediately following collection. Furthermore, retesting of stored DNA samples may be needed in casework for replicate testing, confirmation of results, and to accommodate future testing with new technologies. A novel room temperature DNA storage medium, SampleMatrix™ (SM; Biomatrica, Inc., San Diego, CA), was evaluated for stabilizing and protecting samples. Human genomic DNA samples at varying amounts (0.0625-200 ng) were stored dry in SM for 1 day to 1 year under varying conditions that included a typical ambient laboratory environment and also through successive freeze-thaw cycles (3 cycles). In addition, spiking of 1-4 × SM into samples prior to analysis was performed to determine any inhibitory effects of SM. Quantification of recovered DNA following storage was determined by quantitative PCR or by agarose gel electrophoresis, and evaluation of quantitative peak height results from multiplex short tandem repeat (STR) analyses were performed to assess the efficacy of SM for preserving DNA. Results indicate no substantial differences between the quality of samples stored frozen in liquid and those samples maintained dry at ambient temperatures protected in SM. For long-term storage and the storage of low concentration samples, SM provided a significant advantage over freezer storage through higher DNA recovery. No detectable inhibition of amplification was observed at the recommended SM concentration and complete profiles were obtained from genomic DNA samples even in the presence of higher than recommended concentrations of the SM storage medium. The ability to stabilize and protect DNA from degradation at ambient temperatures for extended time periods could have tremendous impact in simplifying and improving sample storage conditions and requirements. The current work focuses on forensics analysis; however this technology is applicable to all endeavors requiring storage of DNA.


Asunto(s)
ADN/química , Genética Forense , Manejo de Especímenes , Temperatura , Humanos
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