Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 810
Filtrar
1.
J Asian Nat Prod Res ; : 1-18, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287960

RESUMO

This study aimed to investigate the effects of wild Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) rats through metabolomics approach, combined with biochemical parameters evaluations. Consequently, C. sinensis exhibited regulatory effects on the lung's metabolic profiles in COPD rats. Treatment with C. sinensis potentially modulated glycerophospholipid metabolism, glutathione metabolism, and tryptophan metabolism, thereby alleviating oxidative stress (by decreasing MDA and GSSG, while increasing SOD and GSH) and inflammatory response (by inhibiting TNF-α, IL-8, and MMP-9) in COPD rats while improving lung tissue damage.

2.
Front Cell Dev Biol ; 12: 1432444, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220684

RESUMO

Fragile X Syndrome (FXS) is a genetic neurodevelopmental disorder closely associated with intellectual disability and autism spectrum disorders. The core of the disease lies in the abnormal expansion of the CGG trinucleotide repeat sequence at the 5'end of the FMR1 gene. When the repetition exceeds 200 times, it causes the silencing of the FMR1 gene, leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). Although the detailed mechanism by which the CGG repeat expansion triggers gene silencing is yet to be fully elucidated, it is known that this process does not alter the promoter region or the coding sequence of the FMR1 gene. This discovery provides a scientific basis for the potential reversal of FMR1 gene silencing through interventional approaches, thereby improving the symptoms of FXS. Epigenetics, a mechanism of genetic regulation that does not depend on changes in the DNA sequence, has become a new focus in FXS research by modulating gene expression in a reversible manner. The latest progress in molecular genetics has revealed that epigenetics plays a key role in the pathogenesis and pathophysiological processes of FXS. This article compiles the existing research findings on the role of epigenetics in Fragile X Syndrome (FXS) with the aim of deepening the understanding of the pathogenesis of FXS to identify potential targets for new therapeutic strategies.

3.
Heliyon ; 10(16): e35949, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39220919

RESUMO

Purpose: Systemic lupus erythematosus (SLE) is largely caused by B cell dysfunction. JunD is an activator protein 1 family protein that has been linked to the regulation of apoptotic and proliferative activities. However, the precise mechanism(s) by which JunD functions remains to be fully elucidated. Accordingly, this study aimed to clarify the functional importance of JUND gene expression in SLE, with further analyses of the functional role that JunD plays as a regulator of B cell proliferation and immune function. Methods: Reverse transcriptase quantitative polymerase chain reaction techniques were used to analyze JunD expression in B cells of patients with SLE and healthy subjects. Cell Counting Kit-8 (CCK-8) assays and flow cytometry methods were used to characterise proliferative activity, cell cycle progression, and apoptosis of B cells in which JunD was either knocked down or overexpressed. The immune status and autophagic activity of these cells were assessed using Western immunoblotting and enzyme-linked immunosorbent assay (ELISA). Additionally, a JunD knockdown mouse model was established, and the functional role of B cell JunD expression in the pathogenesis of SLE was assessed using Western immunoblotting, ELISA, and haematoxylin and eosin staining. Results: B cells from patients with SLE exhibited upregulation of JunD, with overexpression facilitating in vitro cellular proliferation and modulation of the immune and autophagic status of these B cells. JunD knockdown was also sufficient to modulate in vivo immune function and the autophagic status of B cells. Conclusion: JunD was upregulated in the B cells of patients with SLE, where it regulates proliferation, autophagy, and immunity.

4.
Foods ; 13(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39272573

RESUMO

Cronobacter sakazakii (C. sakazakii) is a foodborne pathogen capable of causing severe infections in newborns. The PhoP/PhoQ two-component system exerts a significant influence on bacterial virulence. This study aimed to investigate the impact of the PhoP/PhoQ system on intestinal inflammation in neonatal mice induced by C. sakazakii. Neonatal mice were infected orally by C. sakazakii BAA-894 (WT), a phoPQ-gene-deletion strain (ΔphoPQ), and a complementation strain (ΔphoPQC), and the intestinal inflammation in the mice was monitored. Deletion of the phoPQ gene reduced the viable count of C. sakazakii in the ileum and alleviated intestinal tissue damage. Moreover, caspase-3 activity in the ileum of the WT- and ΔphoPQC-infected mice was significantly elevated compared to that of the ΔphoPQ and control groups. ELISA results showed elevated levels of TNF-α and IL-6 in the ileum of the mice infected with WT and ΔphoPQC. In addition, deletion of the phoPQ gene in C. sakazakii resulted in a down-regulation of inflammatory genes (IL-1ß, TNF-α, IL-6, NF-κB p65, TLR4) within the ileum and decreased inflammation by modulating the TLR4/NF-κB pathway. It is suggested that targeting the PhoP/PhoQ two-component system could be a potential strategy for mitigating C. sakazakii-induced neonatal infections.

5.
Am J Pathol ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39222906

RESUMO

The dysregulation of N6-methyladenosine (m6A) RNA modification is widely recognized for its crucial roles in various diseases, including pulmonary hypertension (PH). Prior studies have highlighted the significant role of methyltransferase-like 3 (METTL3) in the pathogenesis of PH. Nevertheless, the potential and underlying mechanisms of METTL3 and its inhibitors as targets for PH treatment require further elucidation. In this study, we observed increased levels of METTL3 in various rodent models of PH. In vitro studies revealed that METTL3 silencing or treatment with STM2457, a specific METTL3 inhibitor, attenuated the proliferation and migration of pulmonary artery smooth muscle cells stimulated by platelet-derived growth factor-BB or hypoxia. Moreover, in vivo experiments using adeno-associated virus 9-mediated METTL3 silencing or STM2457 inhibition demonstrated improvement in SU5416/hypoxia-induced PH in mice. Additionally, m6A RNA immunoprecipitation analysis identified RBPJ as a gene regulated by METTL3 in rodent models of PH. Loss-of-function studies showed that silencing RBPJ could attenuate the changes in the proliferation and migration of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB or hypoxia. Further studies indicated that METTL3 and YTHDF1 regulate RBPJ mRNA expression in an m6A-dependent manner. These findings indicated that targeting METTL3 may be a promising therapeutic strategy for treating PH, and modulation of RBPJ could offer a potential intervention mechanism.

6.
BMC Med Imaging ; 24(1): 219, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160476

RESUMO

BACKGROUND: Flatfoot is a condition resulting from complex three-dimensional (3D) morphological changes. Most Previous studies have been constrained by using two-dimensional radiographs and non-weight-bearing conditions. The deformity in flatfoot is associated with the 3D morphology of the bone. These morphological changes affect the force line conduction of the hindfoot/midfoot/forefoot, leading to further morphological alterations. Given that a two-dimensional plane axis overlooks the 3D structural information, it is essential to measure the 3D model of the entire foot in conjunction with the definition under the standing position. This study aims to analyze the morphological changes in flatfoot using 3D measurements from weight-bearing CT (WBCT). METHOD: In this retrospective comparative our CT database was searched between 4-2021 and 3-2022. Following inclusion criteria were used: Patients were required to exhibit clinical symptoms suggestive of flatfoot, including painful swelling of the medial plantar area or abnormal gait, corroborated by clinical examination and confirmatory radiological findings on CT or MRI. Healthy participants were required to be free of any foot diseases or conditions affecting lower limb movement. After applying the exclusion criteria (Flatfoot with other foot diseases), CT scans (mean age = 20.9375, SD = 16.1) confirmed eligible for further analysis. The distance, angle in sagittal/transverse/coronal planes, and volume of the two groups were compared on reconstructed 3D models using the t-test. Logistic regression was used to identify flatfoot risk factors, which were then analyzed using receiver operating characteristic curves and nomogram. RESULT: The flatfoot group exhibited significantly lower values for calcaneofibular distance (p = 0.001), sagittal and transverse calcaneal inclination angle (p < 0.001), medial column height (p < 0.001), sagittal talonavicular coverage angle (p < 0.001), and sagittal (p < 0.001) and transverse (p = 0.015) Hibb angle. In contrast, the sagittal lateral talocalcaneal angle (p = 0.013), sagittal (p < 0.001) and transverse (p = 0.004) talocalcaneal angle, transverse talonavicular coverage angle (p < 0.001), coronal Hibb angle (p < 0.001), and sagittal (p < 0.001) and transverse (p = 0.001) Meary's angle were significantly higher in the flatfoot group. The sagittal Hibb angle (B = - 0.379, OR = 0.684) and medial column height (B = - 0.990, OR = 0.372) were identified as significant risk factors for acquiring a flatfoot. CONCLUSION: The findings validate the 3D spatial position alterations in flatfoot. These include the abduction of the forefoot and prolapse of the first metatarsal proximal, the arch collapsed, subluxation of the talonavicular joint in the midfoot, adduction and valgus of the calcaneus, adduction and plantar ward movement of the talus in the hindfoot, along with the first metatarsal's abduction and dorsiflexion in the forefoot.


Assuntos
Pé Chato , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Suporte de Carga , Pé Chato/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X/métodos , Imageamento Tridimensional/métodos , Estudos Retrospectivos , Feminino , Masculino , Adulto Jovem , Adulto , Adolescente , Pé/diagnóstico por imagem
7.
Mol Ther ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39169623

RESUMO

The microcephaly-capillary malformation (MIC-CAP) syndrome is a life-threatening disease caused by biallelic mutations of the STAMBP gene, which encodes an endosomal deubiquitinating enzyme. To establish a suitable preclinical animal model for clinical therapeutic practice, we generated a central nervous system (CNS)-specific Stambp knockout mouse model (Stambp Sox1-cKO) that phenocopies Stambp null mice including progressive microcephaly, postnatal growth retardation and complete penetrance of preweaning death. In this MIC-CAP syndrome mouse model, early-onset neuronal death occurs specifically in the hippocampus and cortex, accompanied by aggregation of ubiquitinated proteins, and massive neuroinflammation. Importantly, neonatal AAV9-mediated gene supplementation of Stambp in the brain could significantly improve neurological defects, sustain growth, and prolong the lifespan of StambpSox1-cKO mice. Together, our findings reveal a central role of brain defects in the pathogenesis of STAMBP deficiency and provide preclinical evidence that postnatal gene replacement is an effective approach to cure the disease.

8.
MedComm (2020) ; 5(9): e701, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39188936

RESUMO

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.

9.
Int J Mol Sci ; 25(15)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39126019

RESUMO

Glutathione S-transferases (GSTs) are members of a protein superfamily with diverse physiological functions, including cellular detoxification and protection against oxidative damage. However, there is limited research on GSTs responding to cadmium (Cd) stress. This study classified 46 GST genes in Dendrobium officinale (D. officinale) into nine groups using model construction and domain annotation. Evolutionary analysis revealed nine subfamilies with diverse physical and chemical properties. Prediction of subcellular localization revealed that half of the GST members were located in the cytoplasm. According to the expression analysis of GST family genes responding to Cd stress, DoGST5 responded significantly to Cd stress. Transient expression of DoGST5-GFP in tobacco leaves revealed that DoGST5 was localized in the cytoplasm. DoGST5 overexpression in Arabidopsis enhanced Cd tolerance by reducing Cd-induced H2O2 and O2- levels. These findings demonstrate that DoGST5 plays a critical role in enhancing Cd tolerance by balancing reactive oxygen species (ROS) levels, offering potential applications for improving plant adaptability to heavy metal stress.


Assuntos
Cádmio , Dendrobium , Regulação da Expressão Gênica de Plantas , Glutationa Transferase , Proteínas de Plantas , Cádmio/toxicidade , Cádmio/metabolismo , Dendrobium/genética , Dendrobium/enzimologia , Dendrobium/efeitos dos fármacos , Dendrobium/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Filogenia , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Família Multigênica , Genoma de Planta
10.
Food Chem X ; 23: 101623, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100245

RESUMO

Beer fish is characterized by its distinctive spicy flavor and strong beer aroma. Currently, there is a lack of comprehensive research analyzing the changes in taste and volatile compounds that occur during the processing of beer fish. Thus, this study used HS-GC-IMS, electronic tongue, and electronic nose to investigate the changes in flavor components during various processing stages of beer fish. The obtained results were subsequently analyzed using multivariate statistical analysis. The results showed that the final beer fish product (SF) had the greatest amount of free amino acids (888.28 mg/100 g), with alanine, glutamic acid, and glycine contributing to the taste of SF. The inosine monophosphate (IMP) content of beer fish meat varied noticeably depending on processing stages, with deep-fried fish (FF) having the greatest IMP content (61.93 mg/100 g), followed by the final product (SF) and ultrasonic-cured fish (UF). A total of 67 volatiles were detected by GC-IMS, mainly consisting of aldehydes, ketones, and alcohols, of which aldehydes accounted for >37%, which had a great influence on the volatile flavor of beer fish. The flavor components' composition varied noticeably depending on the stage of processing. PLS-DA model screened 35 volatile flavor components (VIP > 1) as markers; the most significant differences were 1-propanethiol, isoamyl alcohol, ethanol, and eucalyptol. Ultrasonic processing, frying, and soaking sauce can significantly improve the formation of flavor compounds, resulting in a notable enhancement of the final beer fish's umami taste and overall flavor quality.

11.
Neurotherapeutics ; : e00430, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39129094

RESUMO

While guidelines recommend 150 â€‹min of moderate to vigorous physical activity (MVPA) weekly to enhance health, it remains unclear whether concentrating these activities into 1-2 days of the week, "weekend warrior" (WW) pattern, has the same benefit for neurodegenerative diseases (NDDs). This study aimed to evaluate the associations of WW pattern and the risk of NDDs. This prospective study was conducted using accelerometer-based physical activity data for a full week from June 2013 to December 2015 in the UK Biobank. These individuals were categorized into distinct physical activity patterns, including the WW pattern (i.e., over 50% or 75% of recommended MVPA achieved over 1-2 days), regular pattern, and inactive pattern. Cox proportional hazards model was used to evaluate the association between physical activity patterns and outcomes. Compared to inactive group, WW pattern and regular pattern was similarly linked to a reduced risk of all-cause dementia (WW: Hazard Ratio [HR]: 0.68, 95% Confidence Interval [CI]: 0.56-0.84; regular: HR: 0.86, 95% CI: 0.67-1.1) and all-cause Parkinsonism (WW: HR: 0.47, 95% CI: 0.35-0.63; regular: HR: 0.69, 95% CI: 0.5-0.95). When the exercise threshold was increased to 75% of MVPA, both patterns still were associated with decreased risk of incident all-cause dementia (WW: HR: 0.61, 95% CI: 0.41-0.91; regular: HR: 0.76, 95% CI: 0.63-0.92) and all-cause Parkinsonism (WW: HR: 0.22, 95% CI: 0.10-0.47; regular: HR: 0.59, 95% CI: 0.46-0.75). Concentrating recommended physical activities into 1-2 days per week is associated with a lower incidence of NDDs.

12.
Ultrasound Q ; 40(3)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39190402

RESUMO

ABSTRACT: This study aimed to explore the feasibility of using the ultrasound quantitative scoring system to guide the selection of surgical methods for a cesarean scar ectopic pregnancy (CSEP). A retrospective analysis was conducted of the medical records of 117 cases of patients with a CSEP. All patients underwent transvaginal ultrasound examination before treatment, and the ultrasound results were compared with the results of surgical exploration. The treatment methods that were delivered for the 2 patient groups with CSEP were analyzed, and agreement between the predicted and actual treatment protocols was tested using the kappa consistency test. Residual myometrial thickness at the scar site was mainly concentrated above 3 mm in the low-risk group, with 70 cases accounting for 76.9%, while in the high-risk group, this was primarily in the range of 1-3 mm with 18 cases accounting for 69.2%. The grading of nourishing blood supply to the gestational sac showed that 96.7% of patients in the low-risk group had Grade I and Grade II blood flow, while 84.6% of the high-risk group had Grade I and Grade II blood flow; Grade II blood flow was predominant in the high-risk group. The majority of patients in both the low- and high-risk groups experienced intraoperative blood loss of ≤50 mL (93.9% vs 80.6%, respectively). The consistency test between the actual and predicted treatment methods yielded a kappa coefficient of 0.644, indicating consistency between the two. For patients with CSEP in the low-risk group (score <4), the ultrasound quantitative scoring system could provide individualized assessment and offer clinically valuable treatment protocols.


Assuntos
Cesárea , Cicatriz , Valor Preditivo dos Testes , Gravidez Ectópica , Humanos , Feminino , Gravidez , Cicatriz/diagnóstico por imagem , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/cirurgia , Estudos Retrospectivos , Adulto , Ultrassonografia Pré-Natal/métodos , Ultrassonografia/métodos , Estudos de Viabilidade
13.
ACS Appl Mater Interfaces ; 16(29): 38092-38100, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38990674

RESUMO

The Mn-based polyanion compound Na3MnTi(PO4)3 (NMTP) with a Na superionic conductor (NASICON) structure has attracted incremental attention as a potential cathode material for sodium-ion batteries. However, the occupation of Mn2+ on Na+ vacancies usually leads to severe voltage hysteresis, which in turn results in significant capacity loss, slow Na+ diffusion kinetics, and poor cycling stability. Herein, anion-substituted compounds Na3MnTi(PO4)3-x(SiO4)x (x = 0.1, 0.2, and 0.3) are synthesized. It reveals that the SiO44- substitution could induce partial oxidation of Mn2+ to Mn3+, and the latter has a lower occupancy preference on Na+ vacancies. By the proposed charge compensation strategy, the Mn2+ occupation on Na+ vacancies can be significantly suppressed. As a result, the voltage hysteresis is substantially inhibited, and greatly improved electrochemical performance is achieved. This study offers an alternative strategy to address the voltage hysteresis associated with NMTP and other Mn-based NASICON cathode materials.

14.
J Am Chem Soc ; 146(31): 21490-21495, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39054650

RESUMO

We report herein chemical and electrochemical ammonia oxidation (AO) catalyzed by a Ru complex, [RuII(H2L)(pic)2]2+ [1, H2L = 6,6'-di(1H-pyrazol-3-yl)-2,2'-bipyridine, pic = 4-picoline], where H2L is a tetradentate ligand with a bipyridyl unit connected to two pyrazoles. 1 functions as an efficient electrocatalyst for the oxidation of NH3 to N2, with a low overpotential of 0.51 V vs Fc+/0 and a Faradaic efficiency of 96%. 1 also undergoes catalytic chemical AO using (4-BrPh)3N•+ as an oxidant, with a turnover number for N2 reaching 41. A novel binuclear complex, [RuIII(L)(pic)2(N2)RuIII(L)(pic)2]4+ (2), was isolated and structurally characterized in the catalytic chemical AO by 1. Complex 2 possesses a zigzag dianionic µ-hexazene unit where the N2 derived from ammonia oxidation is bonded to the pyrazoles, with an NN2-NN2 bond length of 1.3091(70) Å. 2 readily releases N2 upon treating with NH3. Based on experimental and DFT studies, in chemical AO the formation of an N-N bond is proposed to occur via bimolecular coupling of a ruthenium pyrazole imido intermediate to give 2; while in electrochemical AO the N-N bond is formed by nucleophilic attack of NH3 on the intermediate.

15.
Bioresour Technol ; 407: 131115, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39013480

RESUMO

This study developed a microelectrolysis-integrated constructed wetland with pyrite filler around the cathode (e-PCW) to treat eutrophic water. Results indicated that e-PCW effectively enhanced pyrite dissolution, converting solid-phase electron donors into bioavailable forms, thereby facilitating the enrichment of various denitrifying bacteria on pyrite surfaces. Importantly, iron-reducing and sulfur-reducing bacteria attached to the pyrite surfaces enhanced the conversion of ferric iron and sulfate, thereby driving iron and sulfur cycles and promoting electron transfer. Therefore, synergistic effects of pyrite and microelectrolysis made e-PCW achieve higher total nitrogen (TN) and total phosphorus (TP) removal efficiencies. With a hydraulic retention time of 24 h, the highest removal efficiencies of TN and TP achieved 78% and 75%, respectively. Furthermore, when eutrophic water containing high concentration of algae was fed into e-PCW, it consistently demonstrated superior TN and TP removal capabilities. This work provides a valuable approach to optimizing constructed wetland technology for treating eutrophic water.


Assuntos
Ferro , Sulfetos , Enxofre , Purificação da Água , Áreas Alagadas , Ferro/química , Sulfetos/química , Purificação da Água/métodos , Eutrofização , Nitrogênio , Fósforo , Eletrodos , Biodegradação Ambiental
16.
Artigo em Inglês | MEDLINE | ID: mdl-39076095

RESUMO

BACKGROUND: Glioblastoma (GBM) severely disrupts the quality of life of patients. Anoikis represents a significant mechanism in cancer invasion and metastasis. Our study focused on the prognostic relationship between the anoikis-associated gene and GBM and its effect on GBM cell progression. METHODS: We downloaded 656 and 979 GBM sample data from TCGA and CGGA cohort datasets, respectively. Fifteen anoikis-associated genes were obtained from the GeneCards database and were subsequently clustered to identify differential genes associated with them. After LAASO screening, the expression values of the 5 differential genes were the sum of LASSO regression coefficients. Survival analysis and ROC curve analysis of anoikis scores were performed using the TCGA training and CGGA validation sets. The prognostic factors were analyzed using Cox regression analysis in GBM. Moreover, CCK-8, colony formation, wound healing, and transwell assay were used to evaluate GBM cell proliferation and migration. RESULTS: Significant differences were observed in the 5-year survival of GBM patients between the two subgroups. Then, our analysis demonstrated that high OCIAD2, FTLP3, IGFBP2, and H19 levels were associated with lower 5-year GBM survival rates, whereas high SFRP2 levels were associated with higher survival rates. Univariate Cox analysis indicated that GBM risk was linked to both anoikis score and grade, while multivariate Cox analysis indicated that GBM risk was associated with both anoikis score and age. Additionally, OCIAD2 was highly expressed in U251MG and T98G cells. Moreover, OCIAD2 silencing inhibited GBM cell proliferation and migration. CONCLUSION: This study demonstrated the potential of the anoikis-associated gene OCIAD2 as a prognostic biomarker for GBM. Furthermore, we validated in vitro that OCIAD2 promoted GBM cell progression.

17.
Int J Mol Sci ; 25(14)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39062952

RESUMO

Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called "Tianma" in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a therapeutic effect on Huntington's disease (HD). In the present study, we evaluated the effect of GAS on the degradation of mutant huntingtin protein (mHtt) by using PC12 cells transfected with N-terminal mHtt Q74. We found that 0.1-100 µM GAS had no effect on the survival rate of Q23 and Q74 PC12 cells after 24-48 h of incubation. The ubiquitin-proteasome system (UPS) is the main system that clears misfolded proteins in eukaryotic cells. Mutated Htt significantly upregulated total ubiquitinated protein (Ub) expression, decreased chymotrypsin-like, trypsin-like and caspase-like peptidase activity, and reduced the colocalization of the 20S proteasome with mHtt. GAS (25 µM) attenuated all of the abovementioned pathological changes, and the regulatory effect of GAS on mHtt was found to be abolished by MG132, a proteasome inhibitor. The autophagy-lysosome pathway (ALP) is another system for misfolded protein degradation. Although GAS downregulated the expression of autophagy markers (LC3II and P62), it increased the colocalization of LC3II with lysosomal associated membrane protein 1 (LAMP1), which indicates that ALP was activated. Moreover, GAS prevented mHtt-induced neuronal damage in PC12 cells. GAS has a selective effect on mHtt in Q74 PC12 cells and has no effect on Q23 and proteins encoded by other genes containing long CAGs, such as Rbm33 (10 CAG repeats) and Hcn1 (>30 CAG repeats). Furthermore, oral administration of 100 mg/kg GAS increased grip strength and attenuated mHtt aggregates in B6-hHTT130-N transgenic mice. This is a high dose (100 mg/kg GAS) when compared with experiments on HD mice with other small molecules. We will design more doses to evaluate the dose-response relationship of the inhibition effect of GAS on mHtt in our next study. In summary, GAS can promote the degradation of mHtt by activating the UPS and ALP, making it a potential therapeutic agent for HD.


Assuntos
Autofagia , Álcoois Benzílicos , Glucosídeos , Proteína Huntingtina , Lisossomos , Complexo de Endopeptidases do Proteassoma , Ubiquitina , Animais , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Ratos , Complexo de Endopeptidases do Proteassoma/metabolismo , Células PC12 , Autofagia/efeitos dos fármacos , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Ubiquitina/metabolismo , Álcoois Benzílicos/farmacologia , Glucosídeos/farmacologia , Camundongos , Doença de Huntington/metabolismo , Doença de Huntington/tratamento farmacológico , Doença de Huntington/genética , Proteólise/efeitos dos fármacos , Mutação
18.
Mitochondrial DNA B Resour ; 9(7): 881-885, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015383

RESUMO

Plantago major (Plantaginaceae) is a medicinal plant in Chinese folk culture, known for its famous medicinal components such as plantagomain. In this study, we conducted genome sequencing of P. major using Illumina sequencing technology. The assembled complete chloroplast genome had a length of 165,044 bp, comprising a large single-copy regions (82,963 bp), a small single-copy regions (4,633 bp), and a pair of inverted repeat regions (38,724 bp). A total of 140 genes were detected, including 94 CDS, 38 tRNA, and 8 rRNA. Phylogenetic analysis revealed a close genetic relationship between P. major and P. rigida. These findings provide valuable data for a comprehensive understanding of the biological characteristics of P. major.

19.
Front Endocrinol (Lausanne) ; 15: 1410369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055063

RESUMO

Obesity, characterized by its complexity and heterogeneity, has emerged as a significant public health concern. Its association with increased incidence and mortality of cardiovascular diseases stems not only from its complications and comorbidities but also from the endocrine effects of adipose tissue. Abdominal aortic aneurysm (AAA), a chronic inflammatory condition, has been closely linked to obesity. Intriguingly, mild obesity appears to confer a protective effect against AAA mortality, whereas severe obesity and being underweight do not, giving rise to the concept of the "obesity paradox". This review aims to provide an overview of obesity and its paradoxical relationship with AAA, elucidate its underlying mechanisms, and discuss the importance of preoperative weight loss in severely obese patients with AAA.


Assuntos
Aneurisma da Aorta Abdominal , Obesidade , Humanos , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/patologia , Obesidade/complicações , Fatores de Risco , Redução de Peso/fisiologia , Paradoxo da Obesidade
20.
Huan Jing Ke Xue ; 45(7): 3839-3848, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022932

RESUMO

In order to control the increasing ozone (O3) pollution in Hebi, Henan Province, clarifying the pollution characteristics of ozone and its precursors is vital. Therefore, we conducted a comprehensive analysis of O3 pollution utilizing the OFP-PMF-EKMA method combined with online hourly resolution monitoring data of conventional pollutants and volatile organic compounds (VOCs) in the summer of 2022 (June-September). Ozone formation potential (OFP) was used to identify the key VOCs species, and the PMF model was used to identify the VOCs emission sources, whereas EKMA curves and scenario analysis were used to identify the main ozone control area in Hebi and to determine the reduction ratio of VOCs and NOx in a scientifically refined way. In 2022, Hebi had persistent O3 pollution, with the highest concentration in June. Conditions of high temperature, low humidity, and low atmospheric pressure contributed to the O3 accumulation. Aromatic and oxygenated volatile organic compounds (OVOCs) contributed significantly to the OFP and VOCs fraction, which were the dominant active substance and concentration dominant species. The results of the VOCs source analysis indicated that vehicle exhaust sources (25.3%) were the main source of atmospheric VOCs, followed by process sources (17.7%) and biomass combustion sources (17.6%). Thus, emission sources associated with the combustion of fossil fuels and industrial production emissions were the most urgent sources of atmospheric VOCs to be controlled in Hebi. The O3 generation in Hebi occurred in the VOCs-sensitive zones, and the emission reduction results showed that a synergistic emission reduction of VOCs and nitrogen oxide (NOx) could effectively control O3 pollution with a 75% reduction in VOCs and a 10% reduction in NOx.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA