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1.
bioRxiv ; 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37461736

RESUMEN

Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli including touch, temperature, and pain to the central nervous system. Recent advances in single-cell RNA-sequencing (scRNA-seq) have provided new insights into the diversity of sensory ganglia cell types in rodents, non-human primates, and humans, but it remains difficult to compare transcriptomically defined cell types across studies and species. Here, we built cross-species harmonized atlases of DRG and TG cell types that describe 18 neuronal and 11 non-neuronal cell types across 6 species and 19 studies. We then demonstrate the utility of this harmonized reference atlas by using it to annotate newly profiled DRG nuclei/cells from both human and the highly regenerative axolotl. We observe that the transcriptomic profiles of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The new resources and data presented here can guide future studies in comparative transcriptomics, simplify cell type nomenclature differences across studies, and help prioritize targets for future pain therapy development.

2.
Mol Cell Neurosci ; 126: 103857, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37137383

RESUMEN

The nucleus accumbens (NAc) is a key brain region involved in reward processing and is linked to multiple neuropsychiatric conditions such as substance use disorder, depression, and chronic pain. Recent studies have begun to investigate NAc gene expression at a single-cell resolution, however, our understanding of the cellular heterogeneity of the NAc epigenomic landscape remains limited. In this study, we utilize single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) to map cell-type-specific differences in chromatin accessibility in the NAc. Our findings not only reveal the transcription factors and putative gene regulatory elements that may contribute to these cell-type-specific epigenomic differences but also provide a valuable resource for future studies investigating epigenomic changes that occur in neuropsychiatric disorders.


Asunto(s)
Epigenómica , Núcleo Accumbens , Ratones , Animales , Núcleo Accumbens/metabolismo , Cromatina/metabolismo , Factores de Transcripción/metabolismo , Encéfalo/metabolismo
3.
Artículo en Inglés | MEDLINE | ID: mdl-36081878

RESUMEN

Background: The Society of Interdisciplinary Placebo Studies (SIPS) was one of many organizations that hosted a virtual scientific conference in response to the COVID-19 pandemic restrictions. Retaining essential benefits of an in-person conference experience was a primary objective for the SIPS conference planning committee and guided the selection of a virtual platform on which to host the 2021 meeting. This article reports on the methods used to design and analyze an engaging, virtual scientific conference, along with the findings and implications for future meetings. Methods: Participant use of and interaction with different features of the conference platform were recorded and exported for analysis. Additionally, all SIPS conference attendees were invited to complete a brief, online post-conference survey that inquired about their perceptions of the SIPS conference specifically as well as their opinions of virtual and hybrid conferences in general. Using these data, we assessed (1) attendance patterns, (2) level of engagement, and (3) attendee satisfaction. Results: The platform recorded 438 unique, active conference attendees who used either a mobile app, web browser, or both to participate during the 3-day program. Seventy-four percent (N = 324) of active users attended all 3 days with 30 and 26 new attendees on Days 2 and 3, respectively. The connections feature offered on the platform was the most utilized function within the online forum. Attendance in the parallel workshop sessions remained constant across the 3 days, with an average of 44.6% (SD = 6.77) of people moving between workshops within a single session. The two poster sessions had an average of 47.6 (SD = 17.97) and 27.8 (SD = 10.24) unique views per poster, respectively. Eleven percent (N = 48) of attendees completed the post-conference survey. Thirty-six percent of these responders stated they were only able to attend because the conference was offered virtually. Further, the quality of the conference had an average satisfaction rating of 68.08 out of 100 (SD = 22.94). Conclusion: Results of data analyses suggest the virtual platform allowed for those who were unable to attend to join virtually, produced moderate engagement throughout the conference, and that the majority of attendees were satisfied with the quality of the fully-virtual conference. Therefore, incorporating virtual aspects in future in-person conferences could enhance conference experience and participation.

4.
Environ Sci Pollut Res Int ; 28(44): 61929-61950, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34553283

RESUMEN

Energy is a key attribute that is used to evaluate the economic development of any country. The demand for energy is going to rise in developing countries and will be 67% of global use by 2040. The energy surge in these rising economies will be responsible for 60-70% of the global greenhouse gas emissions. The quest for higher energy motivates technological development to curb the climate change occurring with GHG emissions. Carbon dioxide is one of the primary greenhouse gases in the atmosphere. Current work is intended to give an updated review on the different routes of carbon dioxide utilization that are catalytic route, photocatalytic route, electrocatalytic route, microwave plasma route, and biocatalytic route. These routes are capable of converting CO2 into different valuable products such as formic acid, methanol, and di-methyl ether (DME), which are majorly derived from biomass and/or fossil fuels (coal gasification and/or natural gas). This work investigates the effect of different routes available for the production of value-added products by CO2 reduction, discusses various challenges that come across the aforementioned routes, and shares views on future scope and research direction to pave new innovative ways of reducing CO2 from the environment.


Asunto(s)
Dióxido de Carbono , Gases de Efecto Invernadero , Dióxido de Carbono/análisis , Cambio Climático , Carbón Mineral , Combustibles Fósiles , Efecto Invernadero
5.
Eur J Med Chem ; 204: 112640, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32739648

RESUMEN

The over expression of EGFR has been recognized as the driver mechanism in the occurrence and progression of carcinomas such as lung cancer, breast cancer, pancreatic cancer, etcetera. EGFR receptor was thus established as an important target for the management of solid tumors. The occurrence of resistance caused as a result of mutations in EGFR has presented a formidable challenge in the discovery of novel inhibitors of EGFR. This has resulted in the development of three generations of EGFR TKIs. Newer mutations like C797S cause failure of Osimertinib and other EGFR TKIs belonging to the third-generation caused by the development of resistance. In this review, we have summarized the work done in the last five years to overcome the limitations of currently marketed drugs, giving structural activity relationships of quinazoline-based lead compounds synthesized and tested recently. We have also highlighted the shortcomings of the currently used approaches and have provided guidance for circumventing these limitations. Our review would help medicinal chemists streamline and guide their efforts towards developing novel quinazoline-based EGFR inhibitors.


Asunto(s)
Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/química , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , Simulación del Acoplamiento Molecular , Mutación , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad
6.
Eur J Pharm Sci ; 153: 105494, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32730845

RESUMEN

Although there have been many advancements in scientific research and development, the cause of epilepsy still remains an open challenge. In spite of high throughput research in the field of anti-epileptic drugs, efficacy void is still prevalent before the researchers. Researchers have persistently been exploring all the possibilities to curb undesirable side effects of the anti-epileptic drugs or looking for a more substantial approach to diminish or cure epilepsy. The drug development has shown a hope to medicinal chemists and researchers to carry further research by going through a substantial literature survey. This review article attempts to describe the recent developments in the anti-epileptic agents, pertaining to different molecular scaffolds considering their structure-activity relationship, docking studies and their mechanism of actions.


Asunto(s)
Anticonvulsivantes , Epilepsia , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Humanos , Relación Estructura-Actividad
7.
Bioorg Chem ; 89: 103007, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31132600

RESUMEN

Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008-2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/metabolismo , Desarrollo de Medicamentos , Animales , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/química , Humanos , Estructura Molecular , Relación Estructura-Actividad
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