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INTRODUCTION: Left bundle branch area (LBBA) pacing (LBBAP) has been proposed as an alternative therapy option in patients indicated for cardiac pacing to treat bradycardia or heart failure. The aim of the study was to evaluate the safety and effectiveness of LBBAP in patients implanted with a Tendril 2088 stylet-driven lead. METHODS: The international retrospective data collection registry included 11 sites from 5 countries globally. Patients with attempted implants of the Tendril lead in the LBBA were followed for at least 6 months post the implant attempt. The primary safety and efficacy endpoints were freedom from LBBAP lead-related serious adverse events and the composite of LBBA capture threshold of ≤2.0 V and R-wave amplitudes ≥5 mV (or ≥value at implant), respectively. RESULTS: Of 221 patients with attempted implants of the Tendril 2088 lead in the LBBA, 91.4% (202/221) had successful implants for LBBAP. Regardless of the LBBAP implant success, all patients were followed for at least 6 months (8.7 ± 7.3 months). Baseline characteristics: 44% female, 84% ≥65 years old, 34% coronary artery disease, and 86% of primary indications for pacemaker implant. Both primary safety and effectiveness endpoints were met (freedom from LBBAP lead-related serious adverse device effects of 99.5% and electrical performance composite success rate of 93%). The capture thresholds in LBBAP at implant and 6 months were 0.8 ± 0.3 V@0.4 ± 0.1 ms and 0.8 ± 0.3 V@0.4 ± 0.1 ms. The rate of patients with capture threshold rise ≥1 V was 1.5% through 6 months. The R-wave amplitudes in LBBAP at implant and 6 months were 9.3 ± 3.2 mV and 10.6 ± 3.0 mV. CONCLUSIONS: This large multicenter study demonstrates that the stylet-driven Tendril™ STS 2088 lead is safe and effective for LBBAP with high success and low complication rates.
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Potenciales de Acción , Estimulación Cardíaca Artificial , Frecuencia Cardíaca , Marcapaso Artificial , Sistema de Registros , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Factores de Tiempo , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Bradicardia/fisiopatología , Bradicardia/terapia , Bradicardia/diagnóstico , Fascículo Atrioventricular/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Factores de Riesgo , Diseño de EquipoRESUMEN
INTRODUCTION/AIMS: Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. METHODS: This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. RESULTS: Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. DISCUSSION: Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.
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Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Masculino , Femenino , Humanos , Niño , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Fuerza de la Mano/fisiología , Resultado del TratamientoRESUMEN
Shark is a seafood commodity that is a good source of minerals and accumulates heavy metals and trace elements through biomagnification, which can pose health risk if taken above the permissible limit. A study was conducted on commonly landed eleven shark species (Scoliodon laticaudus, Rhizopriodon oligolinx, Sphyrna lewini (CR), Carcharhinus macloti, Carcharinus limbatus, Carcharhinus amblyrhynchoides, Carcharhinus sorrah, Carcharinus falciformes(VU), Glaucostegus granulatus, Chiloscyllium arabicum, Loxodon macrorhinus) and analyzed for their heavy metal content, Hazard Index, Total Hazard Quotient, Metal Pollution Index, and also calculated the health risk associated with the consumption. Most of the heavy metals and trace minerals were found to be within the acceptable limit. The Targeted Hazard Quotient (THQ) and the Hazard Index (HI) of all the species except two were less than 1 (HI ≤ 1.0). The Metal Pollution Index (MPI) is showing either no impact or very low contamination. An overall study on hazard identification and health risk characterization in terms of heavy metals shows contamination of some heavy metals in sharks, but there is no potential human health risk associated with consumption.
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Metales Pesados , Tiburones , Contaminantes Químicos del Agua , Animales , Metales Pesados/análisis , Tiburones/metabolismo , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Humanos , Oligoelementos/análisis , Monitoreo del Ambiente , Minerales/análisisRESUMEN
The tannery is one of the leading revenue-generating sectors in developing countries. The ever-increasing demand for leather products in the global market requires converting large amounts of rawhide/skins into resilient non-putrescible finished leather. Only 20% of the raw material is converted into a finished product; the rest 80% is discarded as solid and liquid wastes during leather processing. A heavy discharge of improperly treated solid tannery waste (STW) causes a severe impact on the surrounding environment by polluting soil, surface water, and groundwater resources, posing severe hazards to human and animal health. STW comprises proteinaceous untanned and tanned waste, which requires proper treatment for eco-friendly disposal. Several strategies have been developed over the years for the reduction and recycling of STW for producing renewable energy (biogas and biohydrogen), biofuels (biodiesel and briquettes), construction material, fertilizers, commercial products (adsorbents, animal feeds, proteins, fats, and enzymes), and biodegradable packaging and non-packaging materials. In this review, we discuss various strategies adopted for recycling, reutilization, and reduction of STW in an environment-friendly manner. Furthermore, an overview of the current perspectives toward achieving a zero-waste policy is also presented to reduce the environmental burden using green-clean technology to aid the survival of present-day tanneries.
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Residuos Sólidos , Administración de Residuos , Humanos , Suelo , Residuos IndustrialesRESUMEN
Cu catalysts are most apt for reducing CO(2) to multi-carbon products in aqueous electrolytes. To enhance the product yield, we can increase the overpotential and the catalyst mass loading. However, these approaches can cause inadequate mass transport of CO(2) to the catalytic sites, which will then lead to H2 evolution dominating the product selectivity. Herein, we use a MgAl LDH nanosheet 'house-of-cards' scaffold to disperse CuO-derived Cu (OD-Cu). With this support-catalyst design, at -0.7â VRHE , CO could be reduced to C2+ products with a current density (jC2+ ) of -1251â mA cm-2 . This is 14× that of the jC2+ shown by unsupported OD-Cu. The current densities of C2+ alcohols and C2 H4 were also high at -369 and -816â mA cm-2 respectively. We propose that the porosity of the LDH nanosheet scaffold enhances CO diffusion through the Cu sites. The CO reduction rate can thus be increased, while minimizing H2 evolution, even when high catalyst loadings and large overpotentials are used.
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Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Descubrimiento de Drogas , Reposicionamiento de Medicamentos/métodos , Animales , Biología Computacional , Femenino , HumanosRESUMEN
The purpose of this study is to provide the results of the newborn screening (NBS) program for Spinal Muscular Atrophy (SMA) in the state of Georgia to determine disease incidence, time to diagnosis and treatment, and early outcomes. NBS for SMA was performed using real time PCR assays from February 2019 through February 2020 in a pilot phase of screening. This method continued as part of our official state panel, and here we describe the pilot period as well as the first year of standard screening through February 2021. Medical records of infants with a positive NBS were reviewed for time to confirmation and neurologic evaluation, SMN2 copy number, clinical information, and treatment. Descriptive statistics were applied. Of the 301,418 samples screened, there were 15 true positive (eight males) and 24 false positive cases. One patient was missed due to human error early in the pilot phase and presented after symptom onset. The incidence of SMA in Georgia is approximately 1 in 18,840 births per year. After the pilot phase, the false positive rate was found to be so low that all patients who test positive were immediately referred to neurology for further care. Four patients died prior to intervention. Ten patients received intervention. Gene therapy was the preferred treatment. One patient was lost to follow-up; another was clinically followed. In conclusion, trends for treated patients show improved or stable motor function. Long-term follow-up will help determine the durability of treatment.
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Atrofia Muscular Espinal , Tamizaje Neonatal , Lactante , Recién Nacido , Masculino , Humanos , Tamizaje Neonatal/métodos , Georgia/epidemiología , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/epidemiología , Atrofia Muscular Espinal/genética , InvestigaciónRESUMEN
Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) roots. Originally discovered in 1961, the biological activities of this molecule against some cancer types was reported during the last decade. Whether PL can synergize with doxorubicin and the underlying mechanism in breast cancer remains elusive. Herein, we report the activities of PL in numerous breast cancer cell lines. PL reduced the migration and colony formation by cancer cells. An enhancement in the sub-G1 population, reduction in the mitochondrial membrane potential, chromatin condensation, DNA laddering and suppression in the cell survival proteins was observed by the alkaloid. Further, PL induced ROS generation in breast cancer cells. While TNF-α induced p65 nuclear translocation, PL suppressed the translocation in cancer cells. The expression of lncRNAs such as MEG3, GAS5 and H19 were also modulated by the alkaloid. The molecular docking studies revealed that PL can interact with both p65 and p50 subunits. PL reduced the glucose import and altered the pH of the medium towards the alkaline side. PL also suppressed the expression of glucose and lactate transporter in breast cancer cells. In tumor bearing mouse model, PL was found to synergize with doxorubicin and reduced the size, volume and weight of the tumor. Overall, the effects of doxorubicin in cancer cells are enhanced by PL. The modulation of glucose import, NF-κB activation and lncRNAs expression may have contributory role for the activities of PL in breast cancer.
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Alcaloides , Antineoplásicos , Neoplasias de la Mama , Dioxolanos , Piper , ARN Largo no Codificante , Alcaloides/farmacología , Alcaloides/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Línea Celular Tumoral , Dioxolanos/farmacología , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Glucosa/farmacología , Humanos , Ratones , Simulación del Acoplamiento Molecular , FN-kappa B/genética , FN-kappa B/metabolismo , Piper/química , ARN Largo no Codificante/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cervical cancer is the most prevalent cancer in females. Melatonin, a neurohormone has been documented as a promising therapeutic molecule for cervical cancer. However, the underlying molecular mechanism is not known. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). The anti-cancer effect of melatonin was evaluated by MTT assay, cell imaging, colony formation, DAPI, AO/PI, LDH, Flow cytometry, scratch assay, western blot analysis and real-time PCR. Results of DAPI, AO/PI, LDH, and Annexin/PI staining revealed that melatonin induces apoptosis. The results of cell cycle analysis revealed that melatonin arrests the HeLa and SiHa cells in sub-G1 and G1 phases, respectively. Western blot analysis revealed that melatonin downregulated the expression of pro-inflammatory transcription factor, NF-κB and the expression of COX-2 protein, a key mediator in cell proliferation. In addition, melatonin downregulated the expression of an invasive marker, MMP-9, an antiapoptotic protein, Bcl-2, and upregulated the expression of pro-apoptotic protein, Bax at both transcriptional and translational levels. Overall, the results suggest that melatonin exhibited strong anti-cancer therapeutic potential against human cervical cancer cell line progression possibly through inhibition of NF-κB signalling pathway.
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Melatonina , Neoplasias del Cuello Uterino , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Melatonina/farmacología , Melatonina/uso terapéutico , FN-kappa B/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: Quantifiable motor strength measures to assess disease severity throughout the continuum of Duchenne muscular dystrophy (DMD) are needed. To study the feasibility of seated trunk strength using hand-held dynamometry (HHD) and caregiver-reported subjective functional independence measures in boys with DMD. METHODS: Prospective, cross-sectional, observational study of 18 participants with DMD enrolled from pediatric muscular dystrophy clinic during routine clinical assessment. Hand-held dynamometry, seated reach distance test and Pediatric Evaluation of Disability Inventory (PEDI) were administered. RESULTS: All study participants regardless of the walking status were able to complete the seated function tests demonstrating feasibility. The age of the participants correlated negatively with PEDI mobility and positively with HHD extension scores. The seated measures did not statistically correlate with PEDI mobility scores. CONCLUSIONS: Seated motor strength measures and PEDI mobility scores are feasible. The PEDI mobility and HHD extension scores correlate with age. Study limitations included single-center experience and cross-sectional data. VIDEO ABSTRACT LINK: https://www.dropbox.com/s/s4r0k7o6s0tfbkb/PT-Seated-Measures-And-DMD-2022.mp4?dl=0.
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Distrofia Muscular de Duchenne , Niño , Estudios Transversales , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , CaminataRESUMEN
Electrocatalytic carbon monoxide reduction has been previously reported to yield a range of carbonaceous products including alcohols, hydrocarbons and carboxylic acids. However, esters, an important family of organic compounds, have not been formed. Herein, we report the electrosynthesis of C3 to C6 acetate esters (H3 C-(C=O)-O-R) from carbon monoxide using copper catalysts in a membrane electrode assembly cell. Ethyl acetate and propyl acetate could be produced with an unprecedented total Faradaic efficiency (FE) of â¼22 % and with a current density of up to -55â mA cm-2 , alongside minor quantities of methyl acetate and butyl acetate. The esters are produced via the addition reaction of ethenone (H2 C=C=O) and alcohols produced during CO reduction. We show that the near water-free reaction conditions and the high local pH play key roles in the formation of the esters.
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Monóxido de Carbono , Ésteres , Acetatos , Alcoholes/química , Electrodos , Ésteres/químicaRESUMEN
Tanneries pose a serious threat to the environment by generating large amount of solid tannery waste (STW). Two metagenomes representing tannery waste dumpsites Jajmau (JJK) and Unnao (UNK) were sequenced using Illumina HiSeq platform. Microbial diversity analysis revealed domination of Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Planctomycetes in both metagenomes. Presence of pollutant degrading microbes such as Bacillus, Clostridium, Halanaerobium and Pseudomonas strongly indicated their bioremediation ability. KEGG and SEED annotated main functional categories included carbohydrate metabolism, amino acids metabolism, and protein metabolism. KEGG displayed 5848 and 9633 proteases encoding ORFs compared to 5159 and 8044 ORFs displayed by SEED classification in JJK and UNK metagenomes, respectively. Abundantly present serine- and metallo-proteases belonging to Bacillaceae, Clostridiaceae, Xanthomonadaceae, Flavobacteriaceae and Chitinophagaceae families exhibited proteinaceous waste degrading ability of these metagenomes. Further structural and functional analysis of metagenome encoded enzymes may facilitate the discovery of novel proteases useful in bioremediation of STW.
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Metagenoma , Residuos Sólidos , Curtiembre , Biodiversidad , Secuenciación de Nucleótidos de Alto Rendimiento , Sistemas de Lectura Abierta , Péptido Hidrolasas/genética , Análisis de Secuencia de ADN , Suelo/químicaRESUMEN
The head and neck squamous cell carcinoma (HNSCC) constitute about 90% of all head and neck cancers. HNSCC falls in the top 10 cancers in men globally. Epoxyazadiradione (EPA) and Azadiradione (AZA) are the limonoids derived from the medicinal plant Azadirachta indica (popularly known as Neem). Whether or not the limonoids exhibit activities against HNSCC and the associated mechanism remains elusive. Herein, we demonstrate that EPA exhibits stronger activity in HNSCC in comparison to AZA. The limonoids obeyed the Lipinski's rule of 5. EPA exhibited activities in a variety of HNSCC lines like suppression of the proliferation and the induction of apoptosis. The limonoid suppressed the level of proteins associated with anti-apoptosis (survivin, Bcl-2, Bcl-xL), proliferation (cyclin D1), and invasion (MMP-9). Further, the expression of proapoptotic Bax and caspase-9 cleavage was induced by the limonoid. Exposure of EPA induced reactive oxygen species (ROS) generation in the FaDu cells. N-acetyl-L-cysteine (ROS scavenger) abrogated the down-regulation of tumorigenic proteins caused by EPA exposure. EPA induced NOX-5 while suppressing the expression of programmed death-ligand 1 (PD-L1). Further, hydrogen peroxide induced NF-κB-p65 nuclear translocation and EPA inhibited the translocation. Finally, EPA modulated the expression of lncRNAs in HNSCC lines. Overall, these results have shown that EPA exhibit activities against HNSCC by targeting multiple cancer related signalling molecules. Currently, we are evaluating the efficacy of this molecule in mice models.
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Antígeno B7-H1/genética , Limoninas/farmacología , NADPH Oxidasa 5/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Factor de Transcripción ReIA/genética , Animales , Apoptosis/efectos de los fármacos , Azadirachta/química , Proliferación Celular/efectos de los fármacos , Ciclina D1/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metaloproteinasa 9 de la Matriz/genética , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Survivin/genéticaRESUMEN
BACKGROUND: Motor unit number index (MUNIX) is a validated electrophysiological biomarker in amyotrophic lateral sclerosis. MUNIX studies in spinal muscular atrophy (SMA) are limited. METHODS: Later-onset SMA children (n = 13; three SMN2 copy number) were evaluated for Hammersmith Motor Function Scale Expanded (HMFSE) and MUNIX of right abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. Age-matched healthy controls (n = 8) were enrolled to obtain normative APB and ADM MUNIX values. RESULTS: Mean APB and ADM MUNIX values in SMA subjects were significantly reduced (P < .001) compared with controls. HMFSE scores strongly correlated with ADM MUNIX (r 0.63). CONCLUSIONS: APB and ADM muscle MUNIX studies are feasible in SMA type 2 children. ADM MUNIX correlated with disease severity on motor function testing. MUNIX studies in later-onset SMA could be a potential biomarker of motor neuron loss.
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Neuronas Motoras/fisiología , Fibras Musculares Esqueléticas/fisiología , Atrofias Musculares Espinales de la Infancia/diagnóstico , Atrofias Musculares Espinales de la Infancia/fisiopatología , Adolescente , Biomarcadores , Niño , Preescolar , Electromiografía , Femenino , Humanos , Masculino , Músculo Esquelético/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been examined against lncRNAs. In some cases, formulation of phytochemicals has also been used. The disease models where phytochemicals have been demonstrated to modulate lncRNAs expression include cancer, rheumatoid arthritis, osteoarthritis, and nonalcoholic fatty liver disease. The regulation of lncRNAs by phytochemicals can affect multi-steps of tumor development. When administered in combination with the conventional drugs, phytochemicals can also produce synergistic effects on lncRNAs leading to the sensitization of cancer cells. Phytochemicals target lncRNAs either directly or indirectly by affecting a wide variety of upstream molecules. However, the potential of phytochemicals against lncRNAs has been demonstrated mostly by preclinical studies in cancer models. How the modulation of lncRNAs by phytochemicals produce therapeutic effects on cancer and other chronic diseases is discussed in this review.
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Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Fitoquímicos/uso terapéutico , ARN Largo no Codificante/genética , Antineoplásicos Fitogénicos/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Humanos , Neoplasias/genética , Resveratrol/uso terapéuticoRESUMEN
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. Chronic inflammation is involved in the recruitment of leukocytes, production of cytokines and chemokines that in turn, lead to survival, metastasis, and angiogenesis in neuroblastoma tumors. The miRNAs and long non-coding (lnc) RNAs have emerged as a novel class of non-coding RNAs that can regulate neuroblastoma associated cell-signaling pathways. The dysregulation of PD-1/PD-L1, inflammatory pathways, lncRNAs, and miRNAs have been reported in clinical and experimental samples of neuroblastoma. These signaling molecules are currently being evaluated for their potential as the biomarker and therapeutic targets in the management of neuroblastoma. A monoclonal antibody called dinutuximab (Unituxin) that attaches to a carbohydrate molecule GD2, on the surface of many neuroblastoma cells, is being used as an immunotherapy drug for neuroblastoma treatment. Atezolizumab (Tecentriq), an engineered monoclonal antibody against PD-L1, are currently in clinical trial for neuroblastoma patients. The lncRNA/miRNA-based therapeutics is being developed to deliver tumor suppressor lncRNAs/miRNAs or silencing of oncogenic lncRNAs/miRNAs. The focus of this review is to discuss the current knowledge on the immune checkpoint molecules, PD-1/PD-L1 signaling, inflammation, and non-coding RNAs in neuroblastoma.
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Antígeno B7-H1/genética , Inflamación/genética , Inflamación/inmunología , Neuroblastoma/genética , Neuroblastoma/inmunología , ARN no Traducido/genética , Animales , Humanos , Oncología Médica/métodosRESUMEN
Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5'-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.
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Antioxidantes/uso terapéutico , Resveratrol/uso terapéutico , Animales , Diabetes Mellitus/tratamiento farmacológico , Humanos , Síndrome Metabólico/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Obesidad/tratamiento farmacológicoRESUMEN
We previously reported a pathogenic de novo p.R342W mutation in the transcriptional corepressor CTBP1 in four independent patients with neurodevelopmental disabilities [1]. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CTBP1 mutation. Within this cohort, we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia, and tooth enamel defects present in most patients. The R342W mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin-modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cell lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes.
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Oxidorreductasas de Alcohol/genética , Proteínas de Unión al ADN/genética , Mutación Missense , Adolescente , Oxidorreductasas de Alcohol/metabolismo , Alelos , Apoptosis , Ataxia/complicaciones , Ataxia/genética , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Niño , Preescolar , Cromatina/química , Proteínas de Unión al ADN/metabolismo , Femenino , Fibroblastos/metabolismo , Glioblastoma/genética , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/genética , Masculino , Hipotonía Muscular/complicaciones , Hipotonía Muscular/genética , Fenotipo , Unión Proteica , Proteómica , Anomalías Dentarias/complicaciones , Anomalías Dentarias/genética , Adulto JovenRESUMEN
AIM: Osteoporosis is one of the diseases which show significant bone mass reduction especially in post menopausal women. The present study was conducted to determine the effect of Bisphosphonates (BP) on alveolar bone and dental implant therapy in women after menopause. MATERIALS AND METHODS: The present study was conducted on 30 postmenopausal women who received at least one dental implant in the last 5 years. Group I comprised of 15 patients who were on BP therapy for 1.5 years, and group II consisted of 15 patients who were on parathyroid hormone (PTH). Bone mineral density (BMD) and bone thickness were assessed in both groups. RESULTS: Group I had 3.85% and group II had 3.15% of dental implants failures. BMD of cortical bone was 1552± 145 mg/mL and 1012 ± 94 mg/mL in groups I and II respectively. BMD of cancellous bone was 80 ± 15 mg/mL and 104 ± 72 mg/mL in group I and group II respectively. The difference was significant (p < 0.05). Cortical bone thickness was 2.5 ± 0.6 mm in group I and 2.2 ± 0.8 mm in group II. The difference was non-significant (p >0.05). There was a reduction in BMD (mg/mL) of cortical and cancellous bone. There was an increase in cortical bone thickness with the use of BPs over the years. The difference was significant (p < 0.05). CONCLUSION: There was a decrease in bone mineral density of both cortical and cancellous bone in both groups. There was increase cortical bone thickness on prolonging use of BPs. CLINICAL SIGNIFICANCE: Patients on BPs therapy should be carefully evaluated both clinically and radiographically before dental implant treatment as these agents affect the quantity and quality of cortical bone especially in the posterior mandibular region in patients with osteoporosis.
Asunto(s)
Implantes Dentales , Densidad Ósea , Tomografía Computarizada de Haz Cónico , Difosfonatos , Femenino , Humanos , PosmenopausiaRESUMEN
Electrodeposition of CuAg alloy films from plating baths containing 3,5-diamino-1,2,4-triazole (DAT) as an inhibitor yields high surface area catalysts for the active and selective electroreduction of CO2 to multicarbon hydrocarbons and oxygenates. EXAFS shows the co-deposited alloy film to be homogeneously mixed. The alloy film containing 6% Ag exhibits the best CO2 electroreduction performance, with the Faradaic efficiency for C2H4 and C2H5OH production reaching nearly 60 and 25%, respectively, at a cathode potential of just -0.7 V vs RHE and a total current density of â¼â¯- 300 mA/cm2. Such high levels of selectivity at high activity and low applied potential are the highest reported to date. In situ Raman and electroanalysis studies suggest the origin of the high selectivity toward C2 products to be a combined effect of the enhanced stabilization of the Cu2O overlayer and the optimal availability of the CO intermediate due to the Ag incorporated in the alloy.