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Latency is the main obstacle towards an HIV cure, with cure strategies aiming to either elicit or prevent viral reactivation. While these strategies have shown promise, they have only succeeded in modulating latency in a fraction of the latent HIV reservoir, suggesting that the mechanisms controlling HIV latency are not completely understood, and that comprehensive latency modulation will require targeting of multiple latency maintenance pathways. We show here that the transcriptional co-activator and the central mediator of canonical Wnt signaling, ß-catenin, inhibits HIV transcription in CD4+ T cells via TCF-4 LTR binding sites. Further, we show that inhibiting the ß-catenin pathway reactivates HIV in a primary TCM cell model of HIV latency, primary cells from cART-controlled HIV donors, and in CD4+ latent cell lines. ß-catenin inhibition or activation also enhanced or inhibited the activity of several classes of HIV latency reversing agents, respectively, in these models, with significant synergy of ß-catenin and each LRA class tested. In sum, we identify ß-catenin as a novel regulator of HIV latency in vitro and ex vivo, adding new therapeutic targets that may be combined for comprehensive HIV latency modulation in HIV cure efforts.
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Infecções por HIV , HIV-1 , beta Catenina , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Ativação Viral , Latência Viral , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the same cannot be said regarding their quality of life. PLWH are affected by comorbid conditions such as high blood pressure, diabetes, and neurocognitive impairment at a higher rate and increased severity than their age-matched counterparts. PLWH also have higher levels of inflammation, the drivers of which are not entirely clear. As cART treatment is lifelong, we assessed here the effects of cART, independent of HIV, on primary human monocyte-derived macrophages (MDMs). MDMs were unskewed or skewed to an alternative phenotype and treated with Atripla or Triumeq, two first-line cART treatments. We report that Triumeq skewed alternative MDMs toward an inflammatory nonsenescent phenotype. Both Atripla and Triumeq caused mitochondrial dysfunction, specifically efavirenz and abacavir. Additionally, transcriptome sequencing (RNA-seq) demonstrated that both Atripla and Triumeq caused differential regulation of genes involved in immune regulation and cell cycle and DNA repair. Collectively, our data demonstrate that cART, independent of HIV, alters the MDM phenotype. This suggests that cART may contribute to cell dysregulation in PLWH that subsequently results in increased susceptibility to comorbidities.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/metabolismo , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/farmacologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Humanos , Macrófagos , Mitocôndrias , Qualidade de VidaRESUMO
Novel methylenedioxyphenyl-based amides, especially N-(4-methoxybenzyl)-6-nitrobenzo-[1,3]-dioxole-5-carboxamide (MDC) and N-(3-acetylphenyl)-6-nitrobenzo-[1,3]-dioxole-5-carboxamide (ADC), potential cardiovascular preventive agents, are successfully synthesized, and their chemical structures are verified by 1H and 13C NMR, Fourier transform infrared (FT-IR), high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction (SC-XRD) analyses. Data obtained from SC-XRD reveal that MDC and ADC are both monoclinic molecules with Z = 2 and 4, respectively. From density functional theory (DFT) calculations, 3.54 and 3.96 eV are the energy gaps of the optimized MDC and ADC structures, respectively. MDC and ADC exhibit an electrophilicity index value of more than 1.5 eV, suggesting that they can act as an electrophile, facilitating bond formation with biomolecules. Hirshfeld surface analysis demonstrates that more than 25% of atomic interactions in both MDC and ADC are from H···H interactions. Based on pharmacokinetic predictions, MDC and ADC exhibit drug-like properties, and molecular docking simulations revealed favorable interactions with active site pockets. Both MDC and ADC achieved higher docking scores of -7.74 and -7.79 kcal/mol, respectively, with myeloperoxidase (MPO) protein. From docking results, MPO was found to be most favorable followed by dipeptidyl peptidase-4 (DPP-4) and α-glucosidase (α-GD). Antioxidant, anti-inflammatory, and in vitro enzymatic studies of MDC and ADC indicate that MDC is more selective toward MPO and more potent than ADC. The application of MDC to inhibit myeloperoxidase could be ascertained to reduce the cardiovascular risk factor. This can be supported from the results of computational docking (based on hydrogen bonding and docking score), in vitro antioxidant and anti-inflammatory properties, and MPO enzymatic inhibition (based on the percentage of inhibition and IC50 values).
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BACKGROUND: The escalating concern over Internet gaming disorder (IGD) among children underscores the urgency of comprehending its determinants and links to mental health, particularly for interventions targeting school-aged children. AIM: This study aimed to evaluate the prevalence and determinants of IGD and its association with depression, anxiety, and behavior among 8-12-year-old children attending private schools in Salem city. SETTINGS AND DESIGN: A cross-sectional study involving 780 children aged 8-12 years from Salem district was conducted. Schools were randomly sampled, and data were collected through a self-administered questionnaire. MATERIALS AND METHODS: Data were gathered from children without genetic, systemic, or mental disorders and brain trauma. The questionnaire, adapted from Alhamoud M A et al. (2022), encompassed sections on sociodemographic characteristics, gaming behavior, and scales for assessing IGD, depression, and anxiety. Administration occurred during school hours with a 30-35 min completion time. STATISTICAL ANALYSIS USED: Data analysis utilized SPSS v23.0, including descriptive statistics, ANOVA, Chi-square tests for intergroup comparisons, and Pearson's correlation coefficient to determine associations. RESULTS: The prevalence of IGD in Salem district was 1.2%, with higher rates of anxiety and depression observed among older children, particularly males. CONCLUSIONS: A positive correlation was evident between IGD, anxiety, and depression. Urgent preventive measures have to be warranted to curb the rising trend of IGD, such as limiting screen time and promoting outdoor activities to enhance children's overall health.
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Ansiedade , Depressão , Transtorno de Adição à Internet , Humanos , Criança , Índia/epidemiologia , Masculino , Estudos Transversais , Prevalência , Feminino , Depressão/epidemiologia , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologia , Ansiedade/epidemiologia , Inquéritos e Questionários , Instituições Acadêmicas , Jogos de Vídeo/estatística & dados numéricos , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/psicologiaRESUMO
Background: Replantation is a commonly performed method for avulsed tooth. A vital periodontal membrane (periodontal ligament [PDL]) is significant for the successful healing of replanted teeth. Hence, various storage media are used to preserve the viability of periodontal cells before replantation. Objectives: The present study was conducted to evaluate the efficacy of ViaSpan, Aloe vera, Gatorade solution, and propolis storage media for maintaining the PDL cell viability. Materials and Methods: The present study was conducted on 40 recently extracted teeth which were randomly divided into four study storage groups: Group I: ViaSpan, Group II: Aloe vera, Group III: Gatorade solution, and Group IV: Propolis. Later they were subjected to centrifugation, and the cells from supernatant were colored with 0.4% trypan blue for determination of viability. The obtained data were statistically evaluated with SPSS package (21.0 version, Inc.; Chicago, IL, USA) using analysis of variance, Mann-Whitney test, and Post hoc tests. Results: The mean viable periodontal cell in Group I was 30.2 cumm, in Group II was 24.6 cumm, Group III was 14.5 cumm, and Group IV in 31.4. The difference was significant (P < 0.01). Post hoc test between different groups revealed a significant difference in mean viable periodontal cells (P < 0.001). Propolis, ViaSpan, and Aloe vera had higher pH and osmolality values. Conclusion: This study found that propolis had higher periodontal cell viability followed by ViaSpan solution and Aloe vera and least in Gatorade solution. Propolis, ViaSpan, and Aloe vera media can be used as a storage media.
Résumé Contexte: la Replantation est une méthode couramment utilisée pour la dent avulsée. Une membrane parodontale vitale (ligament parodontal [PDL]) est important pour la guérison réussie des dents replantées. Par conséquent, divers supports de stockage sont utilisés pour préserver la viabilité du parodontal les cellules avant la réimplantation. Objectifs: la présente étude a été menée pour évaluer L'efficacité de ViaSpan, Aloe vera, solution de Gatorade, et des supports de stockage de propolis pour maintenir la viabilité des cellules PDL. Matériaux et Méthodes: la présente étude a été menée sur 40 récemment dents extraites qui ont été divisées au hasard en quatre groupes de stockage d'étude: Groupe I: ViaSpan, Groupe II: aloe vera, Groupe III: Gatorade solution, et groupe IV: Propolis. Plus tard, ils ont été soumis à une centrifugation et les cellules du surnageant ont été colorées avec 0,4% de trypan bleu pour la détermination de la viabilité. Les données obtenues ont été évaluées statistiquement avec le package SPSS (version 21.0, Inc. Chicago, ILLINOIS, états-unis) en utilisant l'analyse de la variance, le test de Mann-Whitney et les tests post hoc. Résultats: la cellule parodontale viable moyenne dans le Groupe I était de 30,2 cumm, dans Le groupe II était de 24,6 cumm, le Groupe III de 14,5 cumm et le Groupe IV de 31,4. La différence était significative (P < 0,01). Essai post hoc entre différents groupes ont révélé une différence significative dans les cellules parodontales viables moyennes (P < 0,001). Propolis, ViaSpan et aloe vera avaient plus valeurs de pH et d'osmolalité. Conclusion: Cette étude a révélé que la propolis avait une viabilité cellulaire parodontale plus élevée suivie D'une solution de ViaSpan et Aloe vera et moins dans la solution de Gatorade. La Propolis, le ViaSpan et L'aloe vera peuvent être utilisés comme support de stockage. Mots-clés: aloe vera, Gatorade, cellules parodontales, propolis, ViaSpan.
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Aloe , Própole , Adenosina , Alopurinol , Sobrevivência Celular , Glutationa , Humanos , Insulina , Soluções Isotônicas , Soluções para Preservação de Órgãos , Ligamento Periodontal , Própole/farmacologia , RafinoseRESUMO
Total bilirubin values have been used as a potential marker to pre-screen and diagnose various liver-based diseases such as jaundice, bile obstruction, liver cancer, etc. A device known as KromaHealth Kit, composed of paper and an acrylic backbone, is developed to quantify total bilirubin in human serum using image processing and machine learning technology. The biochemical assays are deposited on absorbent paper pads that act as reaction zones when serum is added. A dedicated smartphone app captures images of the colorimetric changes on the pad and converts them into quantitative values of bilirubin. The range of bilirubin concentration that can be quantified using the device ranges from 0.5 mg/dl to 7.0 mg/dl. The precision, limit of detection, interference analysis, linearity, stability, and comparison with a predicate are studied in this paper in accordance with clinical and laboratory standards institute. The results indicate that the KromaHealth Kit can be used as an inexpensive alternative to conventional bilirubin testing in clinical settings. With its level of precision, ease-of-use, long shelf-life, and short turnaround time, it will prove to be invaluable in limited-resource settings.
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A subpopulation within cancer, known as cancer stem cells (CSCs), regulates tumor initiation, chemoresistance, and metastasis. At a closer look, CSCs show functional heterogeneity and hierarchical organization. The present review is an attempt to assign marker profiles to define the functional heterogeneity and hierarchical organization of CSCs, based on a series of single-cell analyses. The evidences show that analogous to stem cell hierarchy, self-renewing Quiescent CSCs give rise to the Progenitor CSCs with limited proliferative capacity, and later to a Progenitor-like CSCs, which differentiates to Proliferating non-CSCs. Functionally, the CSCs can be tumor-initiating cells (TICs), drug-resistant CSCs, or metastasis initiating cells (MICs). Although there are certain marker profiles used to identify CSCs of different cancers, molecules like CD44, CD133, ALDH1A1, ABCG2, and pluripotency markers [Octamer binding transcriptional factor 4 (OCT4), SOX2, and NANOG] are used to mark CSCs of a wide range of cancers, ranging from hematological malignancies to solid tumors. Our analysis of the recent reports showed that a combination of these markers can demarcate the heterogeneous CSCs in solid tumors. Reporter constructs are widely used for easy identification and quantification of marker molecules. In this review, we discuss the suitability of reporters for the widely used CSC markers that can define the heterogeneous CSCs. Since the CSC-specific functions of CD44 and CD133 are regulated at the post-translational level, we do not recommend the reporters for these molecules for the detection of CSCs. A promoter-based reporter for ABCG2 may also be not relevant in CSCs, as the expression of the molecule in cancer is mainly regulated by promoter demethylation. In this context, a dual reporter consisting of one of the pluripotency markers and ALDH1A1 will be useful in marking the heterogeneous CSCs. This system can be easily adapted to high-throughput platforms to screen drugs for eliminating CSCs.
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The Smartphone-based Compression-induced Scope (SCIS) is a mobile device designed to sense the mechanical properties of tumors. Here, an SCIS system with an infrared temperature (SCIS-T) sensor is developed. The color and texture information of target skin are extracted from the SCIST images using a color-based edge detection technique and a texture filter. This new system provides mechanical properties (size, elasticity) of the inclusion as well as the skin surface (color, temperature, texture) characteristics. The application of this system is in the identification of inflammatory breast cancer, which is characterized by color, texture, and temperature change. The device is tested using chicken breast phantoms with embedded silicone inclusion.
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Neoplasias da Mama , Compressão de Dados , Smartphone , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Humanos , TemperaturaRESUMO
Urolithiasis is a painful disorder in which stones are formed in the kidney, bladder or urethra. There are no proper therapeutic treatments available for kidney stones and people suffering from larger stones have to undergo surgery which has many side effects. A natural remedy with therapeutic effects that can dissipate and remove even the larger stones would eliminate the need of a surgery and the risks associated with it. The flowers of Phlogacanthus thyrsiformis used in culinary recipes in the north eastern India are also widely used as a folklore medicine for the treatment of kidney stones and liver disorders. The aim of this study was to evaluate the prophylactic and therapeutic activity of the aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles against struvite urinary stones and calcium oxalate kidney stones. A kidney stone inhibition study was carried out on struvite stones grown in gel medium and calcium oxalate stones in rat models using an aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles. The aqueous extract of P. thyrsiformis flowers and their biofabricated silver nanoparticles, obtained by a green synthetic method, were used to treat struvite urinary stones in vitro and calcium oxalate kidney stones in vivo. Struvite stones were grown in tubes by gel diffusion technique and were treated with varying concentrations of the extract and its nanoparticles. The size of the struvite stones was monitored for 96h using a travelling microscope. Calcium oxalate stones were induced in male Wistar rats by feeding ethylene glycol-ammonium chloride mixture for 14days. Both, prophylactic and therapeutic activities were evaluated by analyzing the urine, serum and histopathological parameters of the rats. The qualitative screening of water extract unveiled the presence of flavonoids as a major constituent. Both, the extract and the nanoparticles effectively reduced the size of struvite stones in vitro and eliminated calcium oxalate stones in Wistar rats in vivo. The potent therapeutic activity of both extract and silver nanoparticles was observed as compared to preventive activity. Anti-urolithiatic potency can be attributed to the presence of flavonoids.
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Flores/química , Lamiales/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prata/química , Urolitíase/induzido quimicamente , Urolitíase/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Nanopartículas Metálicas/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Urolitíase/sangue , Urolitíase/urinaRESUMO
OBJECTIVE There has been a transition from long- to short-segment instrumentation for unstable burst fractures to preserve motion segments. Circumferential fixation allows a stable short-segment construct, but the associated morbidity and complications are high. Posterior short-segment fixation spanning one level above and below the fractured vertebra has led to clinical failures. Augmentation of this method by including the fractured level in the posterior instrumentation has given promising clinical results. The purpose of this study is to compare the biomechanical stability of short-segment posterior fixation including the fractured level (SSPI) to circumferential fixation in thoracolumbar burst fractures. METHODS An unstable burst fracture was created in 10 fresh-frozen bovine thoracolumbar spine specimens, which were grouped into a Group A and a Group B. Group A specimens were instrumented with SSPI and Group B with circumferential fixation. Biomechanical characteristics including range of motion (ROM) and load-displacement curves were recorded for the intact and instrumented specimens using Universal Testing Device and stereophotogrammetry. RESULTS In Group A, ROM in flexion, extension, lateral flexion, and axial rotation was reduced by 46.9%, 52%, 49.3%, and 45.5%, respectively, compared with 58.1%, 46.5%, 66.6%, and 32.6% in Group B. Stiffness of the construct was increased by 77.8%, 59.8%, 67.8%, and 258.9% in flexion, extension, lateral flexion, and axial rotation, respectively, in Group A compared with 80.6%, 56.1%, 82.6%, and 121.2% in Group B; no statistical difference between the two groups was observed. CONCLUSIONS SSPI has comparable stiffness to that of circumferential fixation.
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Fixação Interna de Fraturas/métodos , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Animais , Fenômenos Biomecânicos , Bovinos , Imageamento Tridimensional , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Movimento (Física) , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/fisiopatologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/fisiopatologia , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
AIM: To compare and evaluate the remineralizing potential of four commercially available products namely SHY-NM, GC Tooth Mousse Plus, ReminPro and Colgate strong teeth on demineralized human teeth. MATERIALS AND METHODS: The study included 50 extracted premolars having 3 × 3 mm window prepared on the middle third of the tooth, which was then subjected to demineralization for 48 hours at 37°C. Teeth were randomly selected and grouped into five study groups of 10 teeth in each. Each group was treated with respective remineralizing agent and sectioned using hard-tissue microtome. Each section obtained was visualized under polarized light microscope and analyzed using Image J software. RESULTS: The statistically evaluated results revealed that SHY-NM has the most remineralizing potential followed by ReminPro, GC Tooth Mousse Plus and fluoridated toothpaste. CONCLUSION: Based on the study, the SHY-NM was superior to the GC Tooth Mousse Plus, ReminPro and Colgate strong teeth on demineralized human teeth. How to cite this article: Rajan R, Krishnan R, Bhaskaran B, Kumar SV. A Polarized Light Microscopic Study to Comparatively evaluate Four Remineralizing Agents on Enamel viz CPP-ACPF, ReminPro, SHY-NM and Colgate Strong Teeth. Int J Clin Pediatr Dent 2015;8(1):42-47.
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Struvite or magnesium ammonium phosphate hexahydrate (MAPH) are biological crystals, found in the kidney, which are formed due to the infection caused by urea splitting bacteria in the urinary tract. The struvite crystals observe different morphologies and were developed using single diffusion gel growth technique. The crystalline nature and its composition were studied from different characterization techniques like X-ray Diffraction (XRD) and FTIR. The dielectric behavior of the developed crystal was studied by varying temperature and at different frequencies. The parameters like dielectric constant, dielectric loss, ac conductivity, ac resistivity, impedance and admittance of the struvite crystals were calculated. The studies proved that the dielectric loss or dissipation heat is high in lower frequencies at normal body temperature, which develops a plasma state in the stones and in turn leads to the disintegration of urinary stones. The dielectric nature of the stones leads to the dielectric therapy, which will be a gateway for future treatment modality for urolithiasis.