RESUMEN
Cholesterol homeostasis in neurons is critical for synapse formation and maintenance. Neurons with impaired cholesterol uptake undergo progressive synapse loss and eventual degeneration. To investigate the molecular mechanisms of neuronal cholesterol homeostasis and its role during synapse development, we studied motor neurons of Caenorhabditis elegans because these neurons rely on dietary cholesterol. Combining lipidomic analysis, we discovered that NCR-1, a lysosomal cholesterol transporter, promotes cholesterol absorption and synapse development. Loss of ncr-1 causes smaller synapses, and low cholesterol exacerbates the deficits. Moreover, NCR-1 deficiency hinders the increase in synapses under high cholesterol. Unexpectedly, NCR-2, the NCR-1 homolog, increases the use of cholesterol and sphingomyelins and impedes synapse formation. NCR-2 deficiency causes an increase in synapses regardless of cholesterol concentration. Inhibiting the degradation or synthesis of sphingomyelins can induce or suppress the synaptic phenotypes in ncr-2 mutants. Our findings indicate that neuronal cholesterol homeostasis is differentially controlled by two lysosomal cholesterol transporters and highlight the importance of neuronal cholesterol homeostasis in synapse development.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Colesterol , Lisosomas , Animales , Caenorhabditis elegans/metabolismo , Lisosomas/metabolismo , Colesterol/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Unión Neuromuscular/metabolismo , Homeostasis , Neuronas Motoras/metabolismo , Sinapsis/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genéticaRESUMEN
On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.
Asunto(s)
Mpox , Humanos , Antígenos Virales , Antivirales , Cidofovir , Mpox/diagnóstico , Mpox/epidemiología , Mpox/terapia , PrevalenciaRESUMEN
Fully understanding traditional Chinese medicines (TCMs) is still challenging because of the extreme complexity of their chemical components and mechanisms of action. The TCM Plant Genome Project aimed to obtain genetic information, determine gene functions, discover regulatory networks of herbal species, and elucidate the molecular mechanisms involved in the disease prevention and treatment, thereby accelerating the modernization of TCMs. A comprehensive database that contains TCM-related information will provide a vital resource. Here, we present an integrative genome database of TCM plants (IGTCM) that contains 14,711,220 records of 83 annotated TCM-related herb genomes, including 3,610,350 genes, 3,534,314 proteins and corresponding coding sequences, and 4,032,242 RNAs, as well as 1033 non-redundant component records for 68 herbs, downloaded and integrated from the GenBank and RefSeq databases. For minimal interconnectivity, each gene, protein, and component was annotated using the eggNOG-mapper tool and Kyoto Encyclopedia of Genes and Genomes database to acquire pathway information and enzyme classifications. These features can be linked across several species and different components. The IGTCM database also provides visualization and sequence similarity search tools for data analyses. These annotated herb genome sequences in IGTCM database are a necessary resource for systematically exploring genes related to the biosynthesis of compounds that have significant medicinal activities and excellent agronomic traits that can be used to improve TCM-related varieties through molecular breeding. It also provides valuable data and tools for future research on drug discovery and the protection and rational use of TCM plant resources. The IGTCM database is freely available at http://yeyn.group:96/.
Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
BACKGROUND: Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. RESULTS: First, we created a mechanically injured mouse model of IUA and restored the mice's vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1ß and TNF-α in blood, and downregulated the TGF-ß1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. CONCLUSIONS: This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.
Asunto(s)
Lactobacillus crispatus , Probióticos , Enfermedades Uterinas , Femenino , Humanos , Ratones , Animales , Enfermedades Uterinas/prevención & control , Estrógenos , Adherencias Tisulares/prevención & control , Modelos Animales de EnfermedadRESUMEN
Consumption of commercial probiotics for health improvement and disease treatment has increased in popularity among the public in recent years. The local shops and pharmacies are brimming with various probiotic products such as probiotic food, dietary supplement and pharmaceuticals that herald a range of health benefits, from nutraceutical benefits to pharmaceutical effects. However, although the probiotic market is expanding rapidly, there is increasing evidence challenging it. Emerging insights from microbiome research and public health demonstrate several potential limitations of the natural properties, regulatory frameworks, and market consequences of commercial probiotics. In this review, we highlight the potential safety and performance issues of the natural properties of commercial probiotics, from the genetic level to trait characteristics and probiotic properties and further to the probiotic-host interaction. Besides, the diverse regulatory frameworks and confusing probiotic guidelines worldwide have led to product consequences such as pathogenic contamination, overstated claims, inaccurate labeling and counterfeit trademarks for probiotic products. Here, we propose a plethora of available methods and strategies related to strain selection and modification, safety and efficacy assessment, and some recommendations for regulatory agencies to address these limitations to guarantee sustainability and progress in the probiotic industry and improve long-term public health and development.