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1.
Biochem Biophys Res Commun ; 721: 150145, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38795633

RESUMEN

Itch, a common somatic sensation, serves as a crucial protective system. Recent studies have unraveled the neural mechanisms of itch at peripheral, spinal cord as well as cerebral levels. However, a comprehensive understanding of the central mechanism governing itch transmission and regulation remains elusive. Here, we report the role of the medial septum (MS), an integral component of the basal forebrain, in modulating the acute itch processing. The increases in c-Fos+ neurons and calcium signals within the MS during acute itch processing were observed. Pharmacogenetic activation manipulation of global MS neurons suppressed the scratching behaviors induced by chloroquine or compound 48/80. Microinjection of GABA into the MS or pharmacogenetic inhibition of non-GABAergic neurons markedly suppressed chloroquine-induced scratching behaviors. Pharmacogenetic activation of the MS-ACC GABAergic pathway attenuated chloroquine-induced acute itch. Hence, our findings reveal that MS has a regulatory role in the chloroquine-induced acute itch through local increased GABA to inhibit non-GABAergic neurons and the activation of MS-ACC GABAergic pathway.

2.
Behav Brain Res ; : 115075, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38815698

RESUMEN

BACKGROUND: The periaqueductal gray (PAG) plays a well-established pivotal role in the descending pain modulatory circuit. The objective of this study was to investigate morphological changes in the astroglia in models that are commonly used in pain and itch studies. METHODS: Five different mouse models of pain, as well as two models of chronic itch, were established using complete Freund's adjuvant (CFA), spared nerve injury (SNI), bone cancer pain (BCP), cisplatin (CIS), and paclitaxel (PTX) for pain, and diphenylcyclopropenone (DCP) and acetone and diethyl ether followed by water (AEW) for chronic itch. von Frey tests and video recordings were employed to assess pain and itching behaviors. The immunofluorescence of S100ß, pSTAT3, and glial fibrillary acidic protein (GFAP) was examined. Two- and three-dimensional studies were used to evaluate changes in astrocyte morphology. RESULTS: Significant scratching was caused by DCP and AEW, whereas the administration of CFA, SNI, BCP, CIS, and PTX produced clear mechanical allodynia. The expression of GFAP in the lPAG/vlPAG was upregulated in CFA, SNI, BCP, CIS, PTX, and DCP mice but decreased in AEW mice. According to Sholl analysis, CFA, SNI, PTX, and BCP mice showed substantially higher astrocyte intersections in the vlPAG, whereas CFA, SNI, BCP, CIS, and DCP mice presented longer peak lengths. In three-dimensional analysis, CFA, SNI, PTX, and DCP mice showed increased astrocyte surface areas, while CIS and AEW mice showed both reduced surface areas and/or volumes of astrocytes. CONCLUSION: The findings showed that different pain and itching conditions have different astrocyte morphologies, and these variations in morphological changes help to explain the pathophysiology of these conditions.

3.
Anim Biosci ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38754853

RESUMEN

Objective: Pine needles are rich in many nutrients and exhibit antibacterial and antioxidant biological activities; however, the effects of different production methods of pine needle additives on the growth performance and intestinal flora of broiler chickens are not known. Methods: Normal diets were supplemented with PNF (Pine Needle Fermentation juice), PNS (Pine Needle Soaking juice), or PNP (Pine Needle Powder), and the associated effects on growth performance, relative organ weights, intestinal development, intestinal histological morphology, intestinal flora, meat quality, and serum indicators in broiler chickens were observed. Results: The results showed that PNF, PNS, and PNP all significantly improved feed utilisation and promoted the growth and development of broilers. All three additives also significantly improved the structure of the intestinal flora, specifically increasing the diversity of bacteria; increasing the abundance of beneficial bacteria, such as Faecalibacterium, Rikenella, and Blautia; and decreasing the abundance of harmful bacteria, such as Staphylococcus. The antioxidant properties of pine needles were also found to intensify lipid metabolic reactions in the blood, thus leading to lower TG and TCHO. Meanwhile, high doses of PNF reduced jejunum and ileum weights and also increased meat yellowness. Lastly, none of PNF, PNS, or PNP had an effect on relative organ weights or intestinal histological morphology. Conclusion: In conclusion, the addition of pine needles to the diet of broiler chickens can effectively promote their growth performance as well as improve their intestinal flora and serum status without side effects; in particular, the dose of 0.2% of either PNF and PNS is expected to have the capacity to replace growth-promoting antibiotics as diet additives.

4.
Antiviral Res ; 226: 105898, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692413

RESUMEN

SARS-CoV-2 continues to threaten human health, antibody therapy is one way to control the infection. Because new SARS-CoV-2 mutations are constantly emerging, there is an urgent need to develop broadly neutralizing antibodies to block the viral entry into host cells. VNAR from sharks is the smallest natural antigen binding domain, with the advantages of small size, flexible paratopes, good stability, and low manufacturing cost. Here, we used recombinant SARS-CoV-2 Spike-RBD to immunize sharks and constructed a VNAR phage display library. VNAR R1C2, selected from the library, efficiently binds to the RBD domain and blocks the infection of ACE2-positive cells by pseudovirus. Next, homologous bivalent VNARs were constructed through the tandem fusion of two R1C2 units, which enhanced both the affinity and neutralizing activity of R1C2. R1C2 was predicted to bind to a relatively conserved region within the RBD. By introducing mutations at four key binding sites within the CDR3 and HV2 regions of R1C2, the affinity and neutralizing activity of R1C2 were significantly improved. Furthermore, R1C2 also exhibits an effective capacity of binding to the Omicron variants (BA.2 and XBB.1). Together, these results suggest that R1C2 could serve as a valuable candidate for preventing and treating SARS-CoV-2 infections.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Tiburones , Anticuerpos de Dominio Único , Glicoproteína de la Espiga del Coronavirus , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Animales , SARS-CoV-2/inmunología , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/genética , Humanos , Tiburones/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Sitios de Unión , Unión Proteica , Biblioteca de Péptidos , Células HEK293 , Mutación
5.
Immunol Lett ; 267: 106865, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705483

RESUMEN

PURPOSE: To investigate the relationship between the lipid profiles of patients with primary Sjögren's syndrome (pSS) and other clinical characteristics, laboratory examination, disease activity, and inflammatory factors. In addition, the risk factors for hyperlipidemia-related complications of pSS and the effect of hydroxychloroquine (HCQ) usage on the lipid profile were incorporated into this study. METHODS: This is a single-center, retrospective study that included 367 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. Initially, demographic information, clinical characteristics, medication records, and complications of the patients were gathered. A case-control analysis compared the 12 systems involvement (ESSDAI domain), clinical symptoms, and laboratory tests between pSS patients with and without dyslipidemia. A simple linear regression model was employed to investigate the relationship between serum lipid profile and inflammatory factors. Logistics regression analysis was performed to assess variables for hyperlipidemia-related complications of pSS. The paired t-test was then used to evaluate the improvement in lipid profile among pSS patients. RESULTS: 48.7 % of all pSS patients had dyslipidemia, and alterations in lipid levels were related to gender, age, and smoking status but not body mass index (BMI). Dyslipidemia is more prevalent in pSS patients who exhibit heightened autoimmunity and elevated levels of inflammation. Higher concentrations of multiple highly inflammatory factors correlate with a more severe form of dyslipidemia. Non-traditional cardiovascular risk factors may contribute to hyperlipidemia-related complications of pSS, such as increased, low complement 3 (C3) and low C4. According to our study, HCQ usage may protect against lipid-related disease in pSS. CONCLUSION: Attention should be paid to the dyslipidemia of pSS. This research aims to clarify the population portrait of pSS patients with abnormal lipid profiles and provides insights into the correlation between metabolism and inflammation in individuals with pSS and the potential role they play in the advancement of the disease. These findings provide novel avenues for further understanding the underlying mechanisms of pSS pathogenesis.


Asunto(s)
Inflamación , Lípidos , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/sangre , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Síndrome de Sjögren/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , China/epidemiología , Lípidos/sangre , Inflamación/sangre , Adulto , Hidroxicloroquina/uso terapéutico , Anciano , Dislipidemias/sangre , Dislipidemias/epidemiología , Factores de Riesgo , Estudios de Casos y Controles , Índice de Severidad de la Enfermedad
6.
aBIOTECH ; 5(1): 94-106, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38576435

RESUMEN

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems, including the constituent elements within and among species. Through various efforts in genomic data archiving, integrative analysis and value-added curation, the National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), has successfully established and currently maintains a vast amount of database resources. This dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research efforts. Here, we present a comprehensive overview of central repositories dedicated to archiving, presenting, and sharing plant omics data, introduce knowledgebases focused on variants or gene-based functional insights, highlight species-specific multiple omics database resources, and briefly review the online application tools. We intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00134-4.

7.
Neuropeptides ; 105: 102428, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38583362

RESUMEN

RNA methylation can epigenetically regulate learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of Vascular dementia (VD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus in models of VD. Through prediction and dual-luciferase reporters validation studies, we observed that miRNA-711 was upregulated after VD and could bind to the 3'-untranslated region of FTO mRNA and regulate its expression in vitro. Methylated RNA immunoprecipitation (MeRIP)-qPCR assay and functional study confirmed that Syn1 was an important target gene of FTO. This suggests that FTO is an important regulator of Syn1. FTO upregulation by inhibition of miR-711 in the hippocampus relieves synaptic association protein and synapse deterioration in vivo, whereas FTO downregulation by miR-711 agomir in the hippocampus leads to aggravate the synapse deterioration. FTO upregulation by inhibition of miR-711 relieves cognitive impairment of rats VD model, whereas FTO downregulation by miR-711 deteriorate cognitive impairment. Our findings suggest that FTO is a regulator of a mechanism underlying RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Disfunción Cognitiva , Hipocampo , MicroARNs , Ratas Sprague-Dawley , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Animales , Masculino , MicroARNs/metabolismo , MicroARNs/genética , Hipocampo/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Ratas , Metilación , Demencia Vascular/metabolismo , Demencia Vascular/genética , Modelos Animales de Enfermedad , Metilación de ARN
9.
J Urol ; 211(5): 648-655, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38591703

RESUMEN

PURPOSE: Benefits of docetaxel-based neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP) remain largely unknown. We explored whether docetaxel-based NCHT would bring pathological benefits and improve biochemical progression-free survival (bPFS) over neoadjuvant hormonal therapy (NHT) in locally advanced prostate cancer. MATERIALS AND METHODS: A randomized trial was designed recruiting 141 locally advanced, high-risk prostate cancer patients who were randomly assigned at the ratio of 2:1 to the NCHT group (75 mg/m2 body surface area every 3 weeks plus androgen deprivation therapy for 6 cycles) and the NHT group (androgen deprivation therapy for 24 weeks). The primary end point was 3-year bPFS. Secondary end points were pathological response including pathological downstaging and minimal residual disease rates. RESULTS: The NCHT group showed significant benefits in 3-year bPFS compared to the NHT group (29% vs 9.5%, P = .002). At a median follow-up of 53 months, the NCHT group achieved a significantly longer median bPFS time than the NHT group (17 months vs 14 months). No significant differences were found between the 2 groups in pathological downstaging and minimal residual disease rates. CONCLUSIONS: NCHT plus RP achieved significant bPFS benefits when compared with NHT plus RP in high-risk, locally advanced prostate cancer. A larger cohort with longer follow-up duration is essential in further investigation.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Docetaxel , Terapia Neoadyuvante , Antagonistas de Andrógenos/uso terapéutico , Estudios Prospectivos , Andrógenos , Neoplasia Residual/cirugía , Prostatectomía , Antígeno Prostático Específico
10.
Cell Rep Med ; 5(4): 101506, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38593808

RESUMEN

Prostate cancer (PCa) is a common malignancy in males. The pathology review of PCa is crucial for clinical decision-making, but traditional pathology review is labor intensive and subjective to some extent. Digital pathology and whole-slide imaging enable the application of artificial intelligence (AI) in pathology. This review highlights the success of AI in detecting and grading PCa, predicting patient outcomes, and identifying molecular subtypes. We propose that AI-based methods could collaborate with pathologists to reduce workload and assist clinicians in formulating treatment recommendations. We also introduce the general process and challenges in developing AI pathology models for PCa. Importantly, we summarize publicly available datasets and open-source codes to facilitate the utilization of existing data and the comparison of the performance of different models to improve future studies.


Asunto(s)
Inteligencia Artificial , Neoplasias de la Próstata , Masculino , Humanos , Toma de Decisiones Clínicas
11.
J Med Virol ; 96(4): e29590, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619024

RESUMEN

Our study investigates the molecular link between COVID-19 and Alzheimer's disease (AD). We aim to elucidate the mechanisms by which COVID-19 may influence the onset or progression of AD. Using bioinformatic tools, we analyzed gene expression datasets from the Gene Expression Omnibus (GEO) database, including GSE147507, GSE12685, and GSE26927. Intersection analysis was utilized to identify common differentially expressed genes (CDEGs) and their shared biological pathways. Consensus clustering was conducted to group AD patients based on gene expression, followed by an analysis of the immune microenvironment and variations in shared pathway activities between clusters. Additionally, we identified transcription factor-binding sites shared by CDEGs and genes in the common pathway. The activity of the pathway and the expression levels of the CDEGs were validated using GSE164805 and GSE48350 datasets. Six CDEGs (MAL2, NECAB1, SH3GL2, EPB41L3, MEF2C, and NRGN) were identified, along with a downregulated pathway, the endocannabinoid (ECS) signaling pathway, common to both AD and COVID-19. These CDEGs showed a significant correlation with ECS activity (p < 0.05) and immune functions. The ECS pathway was enriched in healthy individuals' brains and downregulated in AD patients. Validation using GSE164805 and GSE48350 datasets confirmed the differential expression of these genes in COVID-19 and AD tissues. Our findings reveal a potential pathogenetic link between COVID-19 and AD, mediated by CDEGs and the ECS pathway. However, further research and multicenter evidence are needed to translate these findings into clinical applications.


Asunto(s)
Enfermedad de Alzheimer , COVID-19 , Humanos , Enfermedad de Alzheimer/genética , Encéfalo , Análisis por Conglomerados , COVID-19/genética , Endocannabinoides , Proteínas de Microfilamentos , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito
12.
Case Rep Ophthalmol Med ; 2024: 5519361, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566845

RESUMEN

Background: Here, we report a case of a male patient with bilateral focal choroidal excavation (FCE) and central serous chorioretinopathy (CSC). A 33-year-old man complained of mild blurring of vision in the right eye. Optical coherence tomography (OCT) revealed FCE in both eyes, with subretinal fluid in both eyes and serous pigment epithelial detachment in the right eye. Standard laser fluence (50 J/cm2) was used in the right eye, and a subthreshold micropulse laser (SML) was simultaneously used in the left eye. Follow-up visits were recommended. At his last visit (5 months after treatment), the visual acuity was 16/20 in the right eye and 20/20 in the left eye and OCT showed a completed resolution of SRF. Conclusion: FCE is defined as a localized depression of the choroid detected by OCT. It may be congenital or acquired secondarily. We present a case of uncommon focal choroidal excavation and central serous chorioretinopathy (CSC) coexisting in both eyes at a relatively young age in which visual acuity was improved and subretinal fluid (SRF) completely resolved with laser treatment. Timely treatment can promote SRF absorption and improve vision.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38669309

RESUMEN

Porous carbons have shown their potential in sodium-ion batteries (SIBs), but the undesirable initial Coulombic efficiency (ICE) and rate capability hinder their practical application. Herein, learning from nature, we report an efficient method for fabricating a carbon framework (CK) with delicate porous structural regulation by biomimetic mineralization-assisted self-activation. The abundant pores and defects of the CK anode can improve the ICE and rate performance of SIBs in ether-based electrolytes, whereas they are confined in carbonate ester-based electrolytes. Notably, ether-based electrolytes enable CK anode to possess excellent ICE (82.9%) and high-rate capability (111.2 mAh g-1 at 50 A g-1). Even after 5500 cycles at a large current density of 10 A g-1, the capacity retention can still be maintained at 73.1%. More importantly, the full cell consisting of the CK anode and Na3V2(PO4)3 cathode delivers a high energy density of 204.4 Wh kg-1, with a power density of 2828.2 W kg-1. Such outstanding performance of the CK anode is attributed to (1) hierarchical pores, oxygen doping, and defects that pave the way for the transportation and storage of Na+, further enhancing ICE; (2) a high-proportion NaF-based solid-electrolyte-interphase (SEI) layer that facilitates Na+ storage kinetics in ether-based electrolytes; and (3) ether-based electrolytes that determine Na+ storage kinetics further to dominate the performance of SIBs. These results provide compelling evidence for the promising potential of our synthetic strategy in the development of carbon-based materials and ether-based electrolytes for electrochemical energy storage.

14.
Int J Biol Macromol ; 267(Pt 1): 131407, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582463

RESUMEN

Succinate dehydrogenase (SDH) is an important inner mitochondrial membrane-bound enzyme involved in redox reactions during the tricarboxylic acid cycle. Therefore, a series of novel chitosan derivatives were designed and synthesized as potential microbicides targeting SDH and precisely characterized by FTIR, 1H NMR and SEM. Their antifungal and antibacterial activities were evaluated against Botrytis cinerea, Fusarium graminearum, Staphylococcus aureus and Escherichia coli. The bioassays revealed that these chitosan derivatives exerted significant antifungal effects, with four of the compounds achieving 100 % inhibition of Fusarium graminearum merely at a concentration of 0.5 mg/mL. Additionally, CSGDCH showed 79.34 % inhibition of Botrytis cinerea at a concentration of 0.1 mg/mL. In vitro antibacterial tests revealed that CSGDCH and CSGDBH have excellent Staphylococcus aureus and Escherichia coli inhibition with MICs of 0.0156 mg/mL and 0.03125 mg/mL, respectively. Molecular docking studies have been carried out to explore the binding energy and binding mode of chitosan and chitosan derivatives with SDH. The analyses indicated that chitosan derivatives targeted the active site of the SDH protein more precisely, disrupting its normal function and ultimately repressing the growth of microbial cells. Furthermore, the chitosan derivatives were also evaluated biologically for antioxidation, and all of these compounds had a greater degree of reducing power, superoxide radical, hydroxyl radical and DPPH-radical scavenging activity than chitosan. This research has the potential for the development of agricultural antimicrobial agents.


Asunto(s)
Antioxidantes , Quitosano , Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Bases de Schiff , Succinato Deshidrogenasa , Quitosano/química , Quitosano/farmacología , Succinato Deshidrogenasa/antagonistas & inhibidores , Succinato Deshidrogenasa/metabolismo , Succinato Deshidrogenasa/química , Bases de Schiff/química , Bases de Schiff/farmacología , Bases de Schiff/síntesis química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Glicina/química , Glicina/análogos & derivados , Glicina/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Escherichia coli/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Fusarium/efectos de los fármacos , Botrytis/efectos de los fármacos , Técnicas de Química Sintética
15.
Nat Hum Behav ; 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38499771

RESUMEN

Molecules-the elementary units of substances-are commonly considered the units of processing in olfactory perception, giving rise to undifferentiated odour objects invariant to environmental variations. By selectively perturbing the processing of chemical substructures with adaptation ('the psychologist's microelectrode') in a series of psychophysical and neuroimaging experiments (458 participants), we show that two perceptually distinct odorants sharing part of their structural features become significantly less discernible following adaptation to a third odorant containing their non-shared structural features, in manners independent of olfactory intensity, valence, quality or general olfactory adaptation. The effect is accompanied by reorganizations of ensemble activity patterns in the posterior piriform cortex that parallel subjective odour quality changes, in addition to substructure-based neural adaptations in the anterior piriform cortex and amygdala. Central representations of odour quality and the perceptual outcome thus embed submolecular structural information and are malleable by recent olfactory encounters.

16.
Chem Commun (Camb) ; 60(26): 3567-3570, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38465654

RESUMEN

We propose a facile coreduction method to synthesize a platinum-group-metal quaternary alloy anchored on nitrogen-doped hollow carbon spheres (PtPdRuIr/HCS) by using [MClx]y--1-butyl-3-methylimidazole (M = Pt, Pd, Ru, and Ir) ionic liquid. Owing to the steric hindrance of the imidazolium cations, Pt-group metal atoms of different sizes can be deposited at approximately the same pace for the growth of an alloy with lattice defects. The lattice-distorted PtPdRuIr/HCS exhibits enhanced activity toward oxygen electroreduction when benchmarked against Pt counterparts.

17.
Front Immunol ; 15: 1289492, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510251

RESUMEN

Sjögren's syndrome (SjS) is a systemic, highly diverse, and chronic autoimmune disease with a significant global prevalence. It is a complex condition that requires careful management and monitoring. Recent research indicates that epigenetic mechanisms contribute to the pathophysiology of SjS by modulating gene expression and genome stability. DNA methylation, a form of epigenetic modification, is the fundamental mechanism that modifies the expression of various genes by modifying the transcriptional availability of regulatory regions within the genome. In general, adding a methyl group to DNA is linked with the inhibition of genes because it changes the chromatin structure. DNA methylation changes the fate of multiple immune cells, such as it leads to the transition of naïve lymphocytes to effector lymphocytes. A lack of central epigenetic enzymes frequently results in abnormal immune activation. Alterations in epigenetic modifications within immune cells or salivary gland epithelial cells are frequently detected during the pathogenesis of SjS, representing a robust association with autoimmune responses. The analysis of genome methylation is a beneficial tool for establishing connections between epigenetic changes within different cell types and their association with SjS. In various studies related to SjS, most differentially methylated regions are in the human leukocyte antigen (HLA) locus. Notably, the demethylation of various sites in the genome is often observed in SjS patients. The most strongly linked differentially methylated regions in SjS patients are found within genes regulated by type I interferon. This demethylation process is partly related to B-cell infiltration and disease progression. In addition, DNA demethylation of the runt-related transcription factor (RUNX1) gene, lymphotoxin-α (LTA), and myxovirus resistance protein A (MxA) is associated with SjS. It may assist the early diagnosis of SjS by serving as a potential biomarker. Therefore, this review offers a detailed insight into the function of DNA methylation in SjS and helps researchers to identify potential biomarkers in diagnosis, prognosis, and therapeutic targets.


Asunto(s)
Enfermedades Autoinmunes , Síndrome de Sjögren , Humanos , Metilación de ADN , Epigénesis Genética , Regulación de la Expresión Génica
18.
Angew Chem Int Ed Engl ; 63(22): e202403898, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38497553

RESUMEN

Addressing the dual enhancement of circular polarization (glum) and luminescence quantum yield (QY) in circularly polarized luminescence (CPL) systems poses a significant challenge. In this study, we present an innovative strategy utilizing the entropically driven self-assembly of amphiphilic phosphorescent platinum(II) complexes (L-Pt) with tetraethylene glycol chains, resulting in unique temperature dependencies. The entropically driven self-assembly of L-Pt leads to a synergistic improvement in phosphorescence emission efficiency (QY was amplified from 15 % at 25 °C to 53 % at 60 °C) and chirality, both in the ground state and the excited state (glum value has been magnified from 0.04×10-2 to 0.06) with increasing temperature. Notably, we observed reversible modulation of phosphorescence and chirality observed over at least 10 cycles through successive heating and cooling, highlighting the intelligent control of luminescence and chiroptical properties by regulating intermolecular interactions among neighboring L-Pt molecules. Importantly, the QY and glum of the L-Pt assembly in solid state were measured as 69 % and 0.16 respectively, representing relatively high values compared to most self-assembled CPL systems. This study marks the pioneering demonstration of dual thermo-enhancement of phosphorescence and CPL and provides valuable insights into the thermal effects on high-temperature and switchable CPL materials.

19.
J Nutr Biochem ; 127: 109603, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38373507

RESUMEN

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of ß-amyloid (Aß), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aß-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aß-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aß in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aß by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aß-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aß-induced toxicity.


Asunto(s)
Enfermedad de Alzheimer , Ácidos Grasos Omega-3 , Enfermedades Neurodegenerativas , Animales , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/toxicidad , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos Omega-3/farmacología , PPAR gamma/genética , Modelos Animales de Enfermedad
20.
J Biophotonics ; 17(5): e202300448, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38348528

RESUMEN

Photobiomodulation (PBM) has attracted widespread attention in suppressing various pain and inflammation. Primary dysmenorrhea (PD) primarily occurs in adolescents and adult females, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. In this work, the results of pain and PGs demonstrated that 850 nm, 630 nm, and 460 nm all exhibited pain inhibition, decreased PGF2α and upregulated PGE2, while 630 nm PBM has better effectiveness. Then to explore the underlying biological mechanisms of red light PBM on PD, we irradiated prostaglandin-F2α induced HUSM cells and found that low-level irradiance can restore intracellular calcium ion, ROS, ATP, and MMP levels to normal levels. And, red light enhanced cell viability and promoted cell proliferation for normal HUSM cells. Therefore, this study proposes that red light PBM may be a promising approach for the future clinical treatment of PD.


Asunto(s)
Dinoprost , Dismenorrea , Terapia por Luz de Baja Intensidad , Dismenorrea/radioterapia , Femenino , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Humanos , Supervivencia Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Calcio/metabolismo , Línea Celular , Adenosina Trifosfato/metabolismo
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