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L-carnitine (LC), which is a type of quaternary amine, is an essential element for energy metabolism in mammals, plants, and specific bacteria. Originating from the amino acid methionine and lysine, it is primarily synthesized in the kidneys and liver. L-carnitine is a pharmacologically active form of carnitine that plays a vital role in energy generation and the breakdown of fatty acids via ?-oxidation in metabolism. Deficiencies in organic cation transporter-2 (OCTN2) can arise due to gene mutations or in conjunction with other conditions like renal or hepatic disorders. Deficiency in carnitine regulation results in several diseases, including cardiomyopathy, cirrhosis, diabetes, endocrine disorders, malnutrition, aging, sepsis, and malnutrition. LC is known for its anti-inflammatory and antioxidant properties. Research indicates that incorporating LC into the diet can ameliorate inflammatory ailments by decreasing the presence of inflammatory agents. Supplementation with LC is particularly useful for individuals with predominant carnitine deficiencies, which can be life-threatening, as well as certain subsidiary deficiencies like organic acid disorders, muscle wasting, and weakness. Moreover, emerging evidence suggests that LC may have therapeutic benefits for various diseases, including renal diseases, liver diseases, neurodegenerative disorders, cardiovascular diseases (CVDs), cancer, diabetes, cachexia, obesity, depression, and epilepsy.
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Resumen Introducción : El endofenotipo de cáncer de mama triple negativo (TNBC) es uno de los menos frecuentes y sin diana terapéutica, por tanto, se plantea estudiar la correlación del punto de control inmunológico PD-L1 con el establecimiento de microambiente tumoral evaluado por la infiltración linfocitaria intratumoral estromal (TILs) y su importancia en la práctica clínica. Métodos : Se realizó un estudio retrospectivo de casos y controles, con 31 casos de carcinoma infiltrante de la mama triple negativo y 57 controles no pareados de endofenotipo Luminal A, Luminal B y HER-2 atendidos en un año. Se evaluaron las variables: tipo y grado his tológico, expresión PD-L1 con el clon 22C3, TILs, invasión linfovascular, tamaño tumoral, compromiso de ganglios linfáticos y metástasis. El análisis estadístico se ejecutó con la prueba de chi cuadrado y prueba de coeficiente de correlación de Spearman. Resultados : Se encontró una correlación negativa estadísticamente significativa entre TILs y PD-L1 (rho - 0.106, p 0.025), indicando que a mayor expresión de PD-L1, es menor la infiltración linfocitaria intratumo ral. En los grupos de TILs B (10-40% TILs) y C (40-90% TILs) donde se presenta marcado infiltrado inflamatorio intratumoral se evidenció mayor número de pacientes negativos para PD-L1 (CPS <10) con 16 y 10 casos res pectivamente. Para los casos TNBC se logró identificar un coeficiente de asociación negativa (rho -0.378) y con significancia estadística (p 0.01). Discusión : Se estableció la asociación de TNBC, TILs y expresión de PDL1, lo cual es importante para la instau ración de terapias diana y el desarrollo de la medicina de precisión.
Abstract Introduction : Triple negative breast cancer endophe notype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the es tablishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice. Methods : A retrospective case-control study was performed, with 31 cases of triple-negative infiltrat ing breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test. Results : a statistically significant negative correlation was found between TILS and PD-L1 (rho - 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01). Discussion : The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the develop ment of precision medicine.
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SUMMARY: Cadmium (Cd) is a toxic element that accumulates in kidney and liver. L-carnitine(LC) is a natural compound that has been shown to exhibit antioxidant activity. Aim of this study was to investigate the effect of L-carnitine against cadmium-induced changes in liver and kidney tissues in prepubertal female rats. In this study 21-day-old female Wistar Albino rats were used. Control, cadmium (2 mg/kg cadmium intraperitoneally), L-carnitine (300 mg/kg orally) and cadmium+L-carnitine groups were formed. Liver and kidney tissue sections were stained with Hematoxylin-Eosin and Masson Trichrome. Histological scoring was performed in liver and kidney. In the liver tissue given Cd, bile duct proliferation, inflammation cells and connective tissue in the portal area were decreased in treatment group. In kidneys, cadmium group treated with L-carnitine, it was observed that the capillary congestion in the kidneys decreased, but tubular dilatation continued in some places. In fibrosis scoring of the liver groups,statistically significant decrease was observed in the Cd+LC group compared to group of cadmium. In the histological scoring results of the kidney groups, statistically significant decrease in congestion and tubular epithelial degeneration was observed in the group treated with L-carnitine compared to group with cadmium. In conclusion medium-dose cadmium has toxic effects in liver and kidney of prepubertal female rats in subacute period,these effects are alleviated with L-carnitine.
El cadmio (Cd) es un elemento tóxico que se acumula en los riñones y el hígado. La L-carnitina (LC) es un compuesto natural que ha demostrado tener actividad antioxidante. El objetivo de este estudio fue investigar el efecto de la L-carnitina contra los cambios inducidos por el cadmio en los tejidos del hígado y el riñón en ratas hembra prepúberes. En este estudio se utilizaron ratas Wistar Albinas hembra de 21 días de edad. Se formaron grupos control, cadmio (2 mg/kg de cadmio por vía intraperitoneal), L- carnitina (300 mg/kg por vía oral) y cadmio + L-carnitina. Se tiñeron secciones de tejido de hígado y riñón con Hematoxilina-Eosina y tricrómico de Masson. La puntuación histológica se realizó en hígado y riñón. En el tejido hepático que recibió Cd, la proliferación de los conductos biliares, las células inflamatorias y el tejido conectivo en el área portal disminuyeron en el grupo con tratamiento. En los riñones, en el grupo de cadmio tratado con L- carnitina, se observó que la congestión capilar disminuyó, pero la dilatación tubular continuó en algunos sitios. En la puntuación de fibrosis de los grupos de hígado, se observó una disminución estadísticamente significativa en el grupo de Cd+LC en comparación con el grupo de cadmio. Los resultados de puntuación histológica de los grupos de riñón, arrojó una disminución estadísticamente significativa en la congestión y el epitelio tubular Se observó degeneración en el grupo tratado con L-carnitina en comparación con el grupo con cadmio. En conclusión, las dosis medias de cadmio tienen efectos tóxicos en el hígado y los riñones de ratas hembras prepúberes en el período subagudo; estos efectos se alivian con L-carnitina.
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Animais , Feminino , Ratos , Cádmio/toxicidade , Carnitina/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ratos WistarRESUMO
RESUMEN El uso de los coeficientes de cultivo (Kc) en el cultivo de tomate es determinante en la procucción del cultivo permitiendo hacer uso eficiente del recurso hídrico. Esta investigación evaluó el efecto de diferentes Kc en fase de establecimiento (0,1; 0,2 y 0,3) y floración-llenado (0,6; 0,8 y 1.1) sobre dos híbridos, Pietro F1 y Mateus 7370 en invernadero. El diseño experimental desarrollado fue BCA con arreglo en franjas divididas, donde los factores fueron los coeficientes Kc y los híbridos. La evaluación de las variables se realizó en etapa vegetativa y productiva. Los resultados mostraron un comportamiento similar entre los híbridos en la época de establecimiento, caso contrario a la fase de producción ,donde existieron diferencias estadísticas, para las variables número de frutos, peso de fruto y rendimiento, donde el híbrido Pietro, bajo el coeficiente Kc: 1,1 presentó mejores rendimientos y Mateus mejoró su producción, bajo el coeficiente Kc: 0,6.
ABSTRACT The use of crop coefficients (Kc) in tomato crops is decisive in the production, improving the efficient use of water resources. This research evaluated the effect of different Kc in the establishment phase (0.1, 0.2 and 0.3) and flowering-filling (0.6, 0.8 and 1.1) on two hybrids Pietro F1 and Mateus 7370 in greenhouse. The experimental design developed was BCA with a divided strip arrangement where the factors were the Kc coefficients and the hybrids. The evaluation of the variables was carried out in the vegetative and productive stages. The results showed a similar behavior between the hybrids at the establishment time, contrary to the production phase where there were statistical differences for the variables number of fruits, fruit weight and yield, where the Pietro hybrid under Kc coefficient: 1.1 presented better yields and Mateus improved its production under the Kc coefficient: 0.6.
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Background: Walking speed assessments are thought to predict eventual health outcomes and patient quality of life when assessing the physical mobility of an individual. Such performance measurements are functional and objective which gives us accurate interpretation to anticipate future goals. The L-test is a feasible, easy administration in clinical setup would be quick and effortless for physiotherapist professionals. As there is no normative value of L- the test that could interpret the score of the test, our study focuses on finding the cut-off value in older adults aged 60-70 years. Methods: We conducted a cross-sectional study from January 2021 to June 2021 in Mumbai, India. A total of 200 participants were selected based on inclusion criteria. The study used an L-shaped path that is 20 meters long which goes 3 meters straight, then a right turn, followed by 7 meters straight. The subjects walked along the marked pathway and the test completion time was noted. Results: A notable difference was found between the male and female participants with a p value of 0.015 and the test duration for males was 19.15 (16.87-22.64) seconds and for females was 20.22 (18.03-23.94) seconds. A positive weak correlation was found between the body mass index (BMI) and duration. Also, a positive weak correlation was found statistically significant between the age and duration of the test. Conclusions: The study showed that there is an increased time duration of the L test with advancing age and BMI.
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El ser humano está signado por el conflicto, por los deseos contradictorios, por el intercambio nunca simple con los otros. Suponer que el otro debe ser una máquina que siga pautas implica desvitalizarlo, lo que es equivalente al aniquilamiento de lo humano. Las niñas y los niños no tienen que ser encerrados ni con clasificaciones psicopatológicas, ni con medicamentos. Las niñas y los niños tienen que tener un sostén esperanzado por parte del entorno, un suelo a partir del cual puedan desplegar sus alas... Transmitir esperanzas es parte importante de nuestra tarea. Debemos dejar que la vida fluya y aportar para que ese fluir derive en nuevos vuelos AU
The human being is marked by the conflict, the contradictory desires, by the never easy exchange with other people.Supposing that the other person must be a machine which follows guidelines means devitalize him and implies the annihilation of the human being.Girls and boys cannot be bounded, nor with psychopathological classifications either with medicines. Girls and boys must have a hopeful support by their environment, a ground which helps them to open their wings... Giving hope is a very important part of our duty.We must let the life flows and contribute to that flowing leads to new flights AU
L'être humain est marqué par le conflit, par les désirs contradictoires, par l'échange jamais simple avec autrui.Supposer que l'autre doit être une machine qui suit des directives implique de le dévitaliser, ce qui équivaut à l'anéantissement de l'humain.Les filles et les garçons ne doivent pas être enfermés, ni avec des classifications psychopathologiques, ni avec des médicaments.Les filles et les garçons doivent bénéficier du soutien plein d'espoir de leur environnement, d'un terrain à partir duquel ils peuvent déployer leurs ailes...Transmettre l'espoir est une partie importante de notre tâche.Il faut laisser lavie couler et contribuer à ce que ce flux conduise à de nouveaux envols AU
A pessoa humana está marcada pelo conflito, pelos desejos contraditórios, pela troca nunca simples com os outros.Assumir que a outra pessoa deve ser um aparelho que segue directrizes implica desvitalizá-lo, o que equivale à aniquilação do que é humano.As crianças não devem ser trancadas, nem com clasificações psicopatológicas, nem com medicação.As crianças devem ter um apoio esperançoso do seu ambiente, uma base a partir do qual possam abrir suas asas... Transmitir esperanças é uma parte importante da nossa tarefa. Devemos deixar a vida fluir e contribuir para garantir que esse fluxo conduzca a novos voos AU
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Humanos , Pré-Escolar , Criança , Terapia Psicanalítica/métodos , Ética Profissional , Transtornos Mentais/diagnóstico , Psicopatologia/ética , Manual Diagnóstico e Estatístico de Transtornos MentaisRESUMO
En este escrito los autores puntualizan la diferencia entre los conceptos de síntoma y trastorno en la infancia. A los fines diagnósticos establecer esta diferenciación permite pensar estrategias de intervención adecuadas a las características metapsicológicas de estos modos de presentación de sufrimiento en la infancia AU
In this writing the authors point out the difference between the concepts of symptom and disorder in childhood.For diagnostic purposes, establishing this differentiation allows us to think about intervention strategies appropriate to the metapsychological characteristics of these modes of presentation of suffering in childhood AU
Dans cet écrit, les auteurs soulignent la différence entre les concepts de symptôme et de trouble dans l'enfance.À des fins diagnostiques, établir cette différenciation permet de réfléchir à des stratégies d'intervention adaptées aux caractéristiques métapsychologiques de ces modes de présentation de la souffrance dans l'enfance AU
Neste escrito os autores apontam a diferença entre os conceitos de sintoma e transtorno na infância.Para fins diagnósticos, estabelecer essa diferenciação permite pensar estratégias de intervenção adequadas às características metapsicológicas desses modos de apresentação do sofrimento na infancia AU
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Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Psicoterapia/métodos , Sinais e Sintomas , Transtornos Mentais/diagnóstico , Relações Pais-FilhoRESUMO
Saccharum officinarum L. is a useful crop and a member of the Poaceae family that yields sugar molecules with a high concentration. The present study focused on the analysis of qualitative and quantitative phytochemical substances. For the comparative analysis of the crop, we have selected traffic road and non-traffic road sites (control). The qualitative phytochemical substances showed the analysis of protein, carbohydrate, iodine, phenol, tannin, flavonoids, saponin, glycosides, steroid, terpene, and alkaloid, quantitative phytochemical substances of (total phenolic content total mean value 0.03644 ? 0.03240 and total flavonoid content total mean value 0.04772 ? 0.03952). The quality of qualitative and quantitative phytochemical substances in crops growing near traffic roads was reduced. The negative effects of traffic-related air pollution on crop vegetation are clearly shown in this record. Crop vegetation varies between traffic roads and control sites based on analysis of qualitative and quantitative phytochemical substance data.
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Background: Bell抯 palsy is considered as the most frequent cranial neuropathy. Early and adequate risk stratification may help both the patients and the treating physicians in taking informed decisions regarding treatment and understanding their outcomes. We aimed to formulate accessible and sensitive methods of risk stratification in Bell抯 palsy by utilizing electrophysiological and hematological parameters. Methods: We prospectively followed up 101 patients with Bell抯 palsy over a period of 18 months. Electrophysiological parameters were measured thrice i.e., on the first evaluation and after the first week and first month. The N/L, P/L ratio, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were documented in steroid na飗e cases. Patients were graded in severity based on the Sunnybrook and House Brackmann systems. Results: The mean SB and HB grades at admission were 53.89�.725 and 3.92�04 indicating moderate severity. The mean N/L, P/L ratios and ESR on the first day was 3.46�45, 145.42�2.84 and 22.51�.105 respectively. There was no statistical correlation with severity at any time point. The mean CMAP indices on the 1st day, 1st week and 1st month were 0.585�31,0.43�26 and 0.45�23 respectively. The CMAP index at 1 month was correlating with severity. Blink amplitude ratios were correlating with the HB scores at 1 week and 1 month (p<0.0001 both) and the SB score at 1 month (p<0.0001). Conclusions: Hematological parameters were not correlated to disease severity. However, electrophysiological parameters are correlated to disease severity at one week and one month. Blink amplitude ratio may be a useful indicator for risk stratification of Bell抯 palsy patients.
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O conceito de fantasma possui uma importância crucial para o enquadramento da experiência em psicanálise. Este artigo pretende situar o lugar e a função do fantasma neurótico na experiência analítica partindo da função da fala, tal como proposto por Lacan. Para tanto, selecionamos alguns textos e seminários de Lacan situados entre os anos de 1953 a 1964. Nossa hipótese de trabalho consiste na suposição de que, ao enquadrar uma realidade constituída inconscientemente enquanto resposta ao desejo do Outro, o fantasma serve para perpetuar ao neurótico um senso de ser idêntico a si mesmo à medida em que tende a promover um apagamento de contradições provenientes da posição que, como sujeito, ocupa em relação a este desejo. Ao ser concebida como irrupção de um objeto com valor de não-eu no enquadre fantasmático, a angústia produz um efeito reverso, constituindo, por conseguinte, tanto uma contraprova quanto um apoio na demonstração dessa hipótese.
Le concept de fantôme revêt une importance cruciale pour encadrer l'expérience en psychanalyse. Cet article veut situer la place et la fonction du fantasme névrotique dans l'expérience analytique à partir de la fonction de la parole, comme le propose Lacan. Pour cela, nous avons sélectionné quelques textes et séminaires de Lacan situés entre les années 1953 et 1964. Notre hypothèse de travail est qu'en encadrant une réalité inconsciemment constituée en réponse au désir de l'Autre, le fantôme sert à perpétuer chez le névrosé un sentiment d'être identique à lui-même dans la mesure où il tend à favoriser un effacement des contradictions nées de la position qu'il occupe, en tant que sujet, par rapport à ce désir. Conçue comme l'irruption d'un objet ayant valeur de non-moi dans le cadre fantasmatique, l'angoisse produit un effet inverse, constituant donc à la fois une contre-preuve et un support à la démonstration de cette hypothèse.
The concept of the phantasm holds a crucial importance for framing the experience in psychoanalysis. This article aims to situate the place and function of the neurotic phantasm in the analytical experience, starting from the function of speech as proposed by Lacan. To do so, we have selected some texts and seminars by Lacan between the years of 1953 to 1964. Our working hypothesis is that by framing an unconsciously constituted reality as a response to the Other's desire, the phantasm serves to perpetuate in the neurotic subject a sense of being identical to themselves as it tends to promote an erasure of contradictions arising from the subject's position in relation to this desire. When conceived as the irruption of an object with a non-ego value in the phantasmatic frame, anxiety produces a reverse effect, thereby constituting both a counterproof and a support in demonstrating this hypothesis.
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Ansiedade , Psicanálise , Inconsciente PsicológicoRESUMO
Objective: To map the dimensions of quality of life in patients with heart failure (HF) and sarcopenia. Methods: The scoping review will adhere to the JBI Manual for Evidence Synthesis methodology and will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Searches will encompass MEDLINE/PubMed, SCOPUS, EMBASE/Elsevier, LILACS, IBECS, BDENF (BVS), SciELO, Core Collection (Clarivate Analytics), CINAHL, Academic Search Premier (EBSCO), PsycINFO (APA), Cochrane Library, Epistemonikos, and academic search engines: Google Scholar and Bielefeld Academic Search Engine (BASE), without language or date restrictions. Inclusion criteria: Population adults with HF and sarcopenia; Concept Dimensions of quality of life including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression defined based on the EQ-5D-3L questionnaire; Context any health care setting. Two independent reviewers will select studies and extract data, with a third reviewer consulted in cases of discrepancies. Findings will be presented graphically with a narrative summary. Expected results: We aim to uncover key dimensions of quality of life in individuals with HF and sarcopenia through this scoping review. Anticipated outcomes include insights into mobility, self-care, usual activities, pain/discomfort, and anxiety/depression across diverse health care settings. Relevance: This review sheds light on the interplay between HF and sarcopenia and its impact on quality of life. The findings may guide interventions, inform evidence-based decision-making, and contribute to targeted strategies to improve the wellbeing of individuals managing both conditions. Review registration: Open Science Framework [https://archive.org/details/osf-registrations-jn387-v1]. (AU)
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Humanos , Sarcopenia , Insuficiência Cardíaca , Qualidade de VidaRESUMO
This clinical case report aims to describe the development of periradicular and perimplant cystic lesions resulted from the intimate contact of the apical region of osseointegrated implants of dental roots, and discuss the reasons fo r failure of the guided bone regeneration procedure associated with platelet rich fibrin and leukocytes, this process was used to the treatment of the first case. Case Reports. Three cases were reported, two cases described the close contact between the tooth roots and the osseointegrated implants and another with a distance of 1.08 mm. All cases realized a radiographic, and they had not periapical lesions before contact with the apical region of the osseointegrated implants on the roots of the teeth. In the case with the largest cystic extension, the procedure was: removal of the osseointegrated implant with apicectomy of the neighboring teeth, excisional biopsy of the lesion, and grafting using the technique of guided bone regeneration associated with L-PRF. All three cases, endodontic treatment was performed on the neighboring teeth within 2 years of survival of the osseointegrated implants in order to reverse the existing lesion. Results. The diagnostic hypothesis of the three cases was periradicular and peri-implant lesion, arising from a contact of the apical region of the osseointegrated implant with the adja cent tooth. The distance of 1.08 mm between the apices did not ensure normality of the periradicular and peri-implant tissues. The intimate contact caused lesions of different extents and root fractures. Conclusion. Premature contact of the osseointegrated implant with the root region of the neighboring tooth may lead to the development of periradicular and peri-implant lesions, suggesting that it is not possible to control this infectious process with endodontic treatment of the injured tooth.
Este reporte de caso clínico tuvo como objetivo describir el desarrollo de lesiones quísticas perirradiculares y periimplantarias resultantes del contacto íntimo de la región apical de implantes osteointegrados de raíces dentales, y además discutir las razones del fracaso del procedimiento de regeneración ósea guiada asociado a fibrina rica en plaquetas y leucocitos. Este proceso se utilizó para el tratamiento del primer caso. Se reportaron tres casos, en dos casos se describieron el estrecho contacto entre las raíces de los dientes y los implantes osteointegrados y en el otro se determinó una distancia de 1,08 mm. En los tres casos se realizó una radiografía y se determinó que no existían lesiones periapicales, antes del contacto con la región apical de los implantes osteointegrados, en las raíces de los dientes. En el caso de mayor extensión quística, el procedimiento fue: extracción del implante osteointegrado con apicectomía de los dientes vecinos, biopsia excisional de la lesión e injerto mediante la técnica de regeneración ósea guiada asociada a L-PRF. En los tres casos, el tratamiento de endodoncia se realizó en los dientes vecinos dentro de los 2 años de supervivencia de los implantes osteointegrados para revertir la lesión existente. La hipótesis diagnóstica de los tres casos fue lesión perirradicular y periimplantaria, originada por un contacto de la región apical del implante osteointegrado con el diente adyacente. La distancia de 1,08 mm entre los ápices no aseguraba la normalidad de los tejidos perirradiculares y periimplantarios. El contacto íntimo provocó lesiones de diferente extensión y fracturas radiculares. El contacto prematuro del implante osteointegrado con la región radicular del diente vecino puede conducir al desarrollo de lesiones perirradiculares y periimplantarias, lo que sugiere que no es posible controlar este proceso infeccioso con tratamiento endodóntico del diente lesionado.
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Depression is one of the most common mental diseases characterized by mood disorders affecting around 322 million individuals in the world. Depression is a feeling of inadequacy, dejection, anhedonia, and decreased activity in any action. Previously acetyl-L-carnitine reported beneficial effects on lipid metabolism, neuroprotection, and some types of depression. Therefore, in the present study, we evaluated the combined effect of acetyl-L-carnitine and bupropion against experimental-induced depression. Albino rats were divided into different groups (each group contained six animals). Normal groups received saline (1 mL/kg, i.p.). The standard group received imipramine (20 mg/kg, i.p.). The ALC group received acetyl-L-carnitine (100 mg/kg, i.p.), and the BPR group received bupropion (20 mg/kg, i.p.). T I and T II groups received acetyl-L-carnitine (30 mg/kg, i.p.) + Bupropion (10 mg/kg, i.p.) and acetyl-L-carnitine (80 mg/kg, i.p.) + Bupropion (30 mg/kg, i.p.), respectively. Antidepressant effects were assessed by forced swim test and sucrose preference test. In both models, the combined effect of the drug produced a significant (p < 0.05) antidepressant action as compared to the depression control group. Based on the findings, the combined effect of acetyl-L-carnitine and bupropion had a better therapeutic effect to combat depression as compared to individual treatments.
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AIM: To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats, and to explore its possible protective mechanism.METHODS: A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group, blue light injury group, N2L low-dose group(1.0 mg/kg), N2L medium-dose group(2.5 mg/kg), N2L high-dose group(5.0 mg/kg), and physiological saline group, with 6 rats in each group. The normal control group was reared in a 12 h dark and light cycle, and the rest of the groups received 9 h of daily light exposure, 3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 lx, and 12 h of darkness to establish the injury model, and were exposed to light exposure for 14 d. For 14 consecutive durations, a 1 mL dose of the corresponding drug was injected intraperitoneally. The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography. Specimens were prepared by over anesthesia, HE staining, and the thickness of the outer nuclear layer was observed under a optical microscope; superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit; and the retinal Caspase-3, quinone oxidoreductase 1(NQO1), glutathione S transferase(GST), Bcl-2, and Bax protein expression in rat retina were detected by Western blot.RESULTS: The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light, b-wave in bright-vision ERG 3.0(cd·s)/m2 stimulated light, and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P&#x003C;0.01), while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P&#x003C;0.05), and was not statistically different from that of the normal control group; the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P&#x003C;0.001), while in the N2L medium dose group, it was thicker than that of the blue light injury group(P&#x003C;0.001), and there was no statistically significant difference from the normal control group; SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P&#x003C;0.05); the expression of Caspase-3, Bax, and NQO1 in the blue light injury group was higher than that of the normal control group(all P&#x003C;0.01), and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P&#x003C;0.001), whereas GST, NQO1 and Bcl-2 were significantly increased(all P&#x003C;0.01).CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats, and it is expected to be a preventive and curative drug for it.
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Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated.The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated.The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.
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Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.
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@#Objective To construct a yeast two-hybrid recombinant bait plasmid of human programmed cell death ligand 1(PD-L1)immunoglobulin variable region(IgV)domain gene,detect its expression in yeast and detect the cytotoxicity and self-activation of PD-L1 IgV protein as well as the interaction between PD-L1 IgV and human thioredoxin(hTrx).Methods Human PD-L1 was analyzed by bioinformatics method,and primers were designed to amplify PD-L1 IgV domain based on the coding region of PD-L1 gene registered in NCBI GenBank database. PCR amplification was carried out with pENTERPD-L1 plasmid as template,and then cloned into yeast two-hybrid bait vector pGBKT7. The recombinant bait plasmid and pGBKT7 empty vector were transformed into Y2HGold yeast cells respectively,and the PD-L1 IgV gene and its expression were detected by PCR and Western blot;Meanwhile,the protein toxicity and self-activation of PD-L1 IgV were detected,and the interaction between PD-L1 IgV and hTrx was detected by drip plate method.Results The bioinformatics analysis results of PD-L1 were consistent with related reports. The recombinant bait plasmid pGBKT7-PD-L1 IgV was correctly constructed,and Y2HGold positive clone was obtained,in which PD-L1 IgV was stably expressed. The empty vector pGBKT7 and recombinant bait plasmid pGBKT7-PD-L1 IgV grew well on SD/-Trp and SD/-Trp/X-α-Gal plates with the same colony size and number and white colony,but they did not grow on SD/-Trp/X-α-Gal/AbA plates,which indicated that PD-L1 IgV protein had no toxicity and no self-activation effect on yeast. The results of drip plates test showed that all experimental groups grew well on SD/-Trp/-Leu plate,while only positive control group grew on SD/-Trp/-Leu/X-α-Gal/AbA plate and showed blue color,which indicated that bait protein PD-L1 IgV and hTrx did not self-activate,and there was no interaction between them.Conclusion Recombinant human PD-L1 IgV bait plasmid was successfully constructed. PD-L1 IgV protein showed no toxicity and self-activation effect on yeast cells,and there was no interaction between PD-L1 IgV and hTrx. Subsequently,hTrx can be used to construct a peptide aptamer library,from which peptide aptamers that specifically bind to PD-L1 IgV can be screened.
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Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
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Humanos , Antígeno B7-H1/metabolismo , Células-Tronco Mesenquimais/imunologia , Linfócitos T/metabolismo , ImunomodulaçãoRESUMO
Objective To explore the effects of L-carnitine combined with citicoline on the therapeutic effect of neonatal hypoxic-ischemic encephalopathy(NHIE)and serum nitric oxide(NO)and endothelin-1(ET-1).Methods A total of 95 children with HIE admitted to the hospital from April 2020 to January 2023 were selected and were divided into observation group(47 cases)and control group(48 cases)by random number table method.The control group was given citicoline,and the observation group was given citicoline combined with L-carnitine.The therapeutic effect was evaluated on 14 days after treatment,and the recovery time of original reflex,muscle tone and consciousness was calculated.The levels of oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD)]and vascular endothelial function indexes(NO,ET-1)were detected before treatment and 14 days after treatment.Neonatal neurobehavioral score(NBNA)was used to evaluate the neurological function of the children,and the safety of the treatment regimen was ob-served.Pearson correlation analysis was used to analyze the correlation between NBNA and vascular endothe-lial function indexes.Results The total effective rate in the observation group was 91.49%,which was higher than 72.92%in the control group(P<0.05).The original reflex recovery time,muscle tone recovery time and consciousness recovery time of NHIE children in the observation group were shorter than those in the control group(P<0.05).There was no significant difference in NBNA scores between the two groups before treatment(t=1.225,P=0.224).After treatment,the NBNA score in the observation group was higher than that in the control group(t=6.223,P<0.001).After treatment,MDA level decreased and SOD level in-creased in two groups(P<0.05).After treatment,the level of MDA in the observation group was lower than that in the control group,while the level of SOD was higher than that in the control group(P<0.05).After treatment,the levels of NO and ET-1 were decreased in both groups(P<0.05).The levels of NO and ET-1 in the observation group were lower than those in the control group after treatment(P<0.05).The adverse drug reaction rates in observation group and control group were 17.02%and 8.33%,respectively,and there was no significant difference between two groups(P>0.05).Pearson correlation analysis showed that serum NO,ET-1 and NBNA score in NHIE children were negatively correlated(r=-0.546,-0.608,P<0.05).Conclusion L-carnitine combined with citicoline could improve the therapeutic effect of NHIE,shorten the re-covery time of clinical manifestations,and improve nerve function,oxidative stress and vascular endothelial function without increasing drugs and adverse reactions.In addition,vascular endothelial function indexes are negatively correlated with NBNA score,which could be used as auxiliary reference indexes for judging NHIE.
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Objective:To compare and evaluate the quality of wild and different cultivation methods of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai through analysis on UPLC characteristic atlas and multi-component content determination results. Methods:UPLC was used to establish the characteristic chromatogram and multi-component content determination method of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai, and clustering analysis, orthogonal partial least squares - discriminant analysis method were used for chemical pattern recognition analysis. Results:The results showed that there were 10 common peaks in 18 batches of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai. Five components were identified, erythrothioneine(peak 1), protocatechuic acid (peak 2), protocatechualdehyde (peak 3), caffeic acid (peak 4) and Hispidin (peak 5). HCA and OPLS-DA could distinguish Sanghuang porus vaninii (Ljub.) with different cultivation methods. Conclusion:Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai in wood is closer to wild Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai than in substitute cultivation. The UPLC characteristic atlas and multi-component content determination method established in this study can provide reference for the quality evaluation of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai.