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1.
Phytochemistry ; 226: 114206, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972440

RESUMO

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.

2.
J Pineal Res ; 76(5): e12987, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38975671

RESUMO

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.


Assuntos
Ferroptose , Melatonina , Camundongos Knockout , Privação do Sono , Animais , Camundongos , Melatonina/metabolismo , Melatonina/farmacologia , Privação do Sono/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Peroxidação de Lipídeos , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/genética , Araquidonato 12-Lipoxigenase
3.
Front Genet ; 15: 1359108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966010

RESUMO

Purpose: This study aims to assess the causal relationship between Obstructive Sleep Apnea (OSA), dyslipidemia, and osteoporosis using Mendelian Randomization (MR) techniques. Methods: Utilizing a two-sample MR approach, the study examines the causal relationship between dyslipidemia and osteoporosis. Multivariable MR analyses were used to test the independence of the causal association of dyslipidemia with OSA. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on genome-wide significance, independence, and linkage disequilibrium criteria. The data were sourced from publicly available Genome-Wide Association Studies (GWAS) of OSA (n = 375,657) from the FinnGen Consortium, the Global Lipids Genetics Consortium of dyslipidemia (n = 188,577) and the UK Biobank for osteoporosis (n = 456,348). Results: The MR analysis identified a significant positive association between genetically predicted OSA and triglyceride levels (OR: 1.15, 95% CI: 1.04-1.26, p = 0.006) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (OR: 0.84, 95% CI: 0.77-0.93, p = 0.0003). Conversely, no causal relationship was found between dyslipidemia (total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol) and OSA or the relationship between OSA and osteoporosis. Conclusion: The study provides evidence of a causal relationship between OSA and dyslipidemia, highlighting the need for targeted prevention and management strategies for OSA to address lipid abnormalities. The absence of a causal link with osteoporosis and in the reverse direction emphasizes the need for further research in this area.

4.
BMC Pulm Med ; 24(1): 343, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014333

RESUMO

BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.


Assuntos
Calcinose , Mutação , Linhagem , Humanos , Masculino , Calcinose/genética , Calcinose/patologia , Feminino , Dineínas do Axonema/genética , Adulto , Transtornos da Motilidade Ciliar/genética , Encefalopatias/genética , Fenótipo , Células HEK293 , China , Splicing de RNA/genética , Pessoa de Meia-Idade , Glicosídeo Hidrolases
5.
Inflamm Res ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844677

RESUMO

BACKGROUND: Inflammatory macrophage infiltration plays a critical role in acute kidney disease induced by ischemia-reperfusion (IRI-AKI). Calycosin is a natural flavone with multiple bioactivities. This study aimed to investigate the therapeutic role of calycosin in IRI-AKI and its underlying mechanism. METHODS: The renoprotective and anti-inflammatory effects of calycosin were analyzed in C57BL/6 mice with IRI-AKI and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA-seq was used for mechanism investigation. The molecular target of calycosin was screened by in silico methods and validated by surface plasmon resonance (SPR). Macrophage chemotaxis was analyzed using Transwell and agarose gel spot assays. RESULTS: Calycosin treatment significantly reduced serum creatinine and urea nitrogen and attenuated tubular destruction in IRI-AKI mice. Additionally, calycosin markedly suppressed NF-κB signaling activation and the expression of inflammatory mediators IL-1ß and TNF-α in IRI-AKI kidneys and LPS-stimulated RAW 264.7 cells. Interestingly, RNA-seq revealed calycosin remarkably downregulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was downregulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in silico target prediction, molecular docking, and SPR assay demonstrated that calycosin directly binds to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells. CONCLUSIONS: In summary, calycosin attenuates IRI-AKI by inhibiting MIF-mediated macrophage inflammatory chemotaxis, suggesting it could be a promising therapeutic agent for the treatment of IRI-AKI.

6.
RSC Adv ; 14(28): 20056-20060, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911828

RESUMO

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 611-618, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38926378

RESUMO

OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.


Assuntos
Displasia Broncopulmonar , Recém-Nascido Prematuro , Gêmeos , Humanos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/epidemiologia , Fatores de Risco , Recém-Nascido , Feminino , Estudos Retrospectivos , Masculino , Idade Gestacional , Peso ao Nascer , Modelos Logísticos
8.
J Asian Nat Prod Res ; : 1-10, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869219

RESUMO

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors.

9.
Inorg Chem ; 63(28): 13014-13021, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38943593

RESUMO

Zwitterionic thiolate ligands have the potential to introduce novel assembly modes and functions for noble metal clusters. However, their utilization in the synthesis of silver clusters remains understudied, particularly for the clusters containing reductive Ag(0) species. In this article, we report the first synthesis of a mixed-valence silver(0/I) cluster protected by zwitterionic Tab as thiolate ligands (Tab = 4-(trimethylammonio)benzenethiolate), denoted as [Ag22(Tab)24](PF6)20·16CH3OH·6Et2O (Ag22·16CH3OH·6Et2O), alongside an Ag(I) cluster [Ag20(Tab)12(PhCOO)10(MeCN)2(H2O)](PF6)10·11MeCN (Ag20·11MeCN). Ag22 has a distinct hierarchical supratetrahedral structure with a central {Ag6} kernel surrounded by four [Ag4(Tab)6]4+ units. High-resolution electrospray ionization mass spectra demonstrate that Ag22 has two free electrons, indicating a superatomic core. Ag20 has a drum-like [Ag12(Tab)6(PhCOO)6(H2O)]6+ inner core capped by two tetrahedral-like [Ag4(Tab)3(PhCOO)2(MeCN)]2+ units. Ag20 can be transformed into Ag22 after its reaction with NaBH4 in solution. Antibacterial measurements reveal that Ag22 has a significantly lower minimum inhibitory concentration than that of the Ag20 cluster. This work not only extends the stabilization of silver(0/I) clusters to neutral thiol ligands but also offers new materials for the development of novel antibacterial materials.

10.
Bioorg Chem ; 148: 107478, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788366

RESUMO

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.


Assuntos
Alcaloides , Antineoplásicos Fitogênicos , Apoptose , Proliferação de Células , Delphinium , Diterpenos , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Ovarianas , Feminino , Humanos , Delphinium/química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Relação Estrutura-Atividade , Animais , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular
11.
BMC Pulm Med ; 24(1): 248, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764064

RESUMO

BACKGROUND: Neuronal guanine nucleotide exchange factor (NGEF) plays a key role in several cancers; however, its role in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to evaluate the efficacy of NGEF as a prognostic biomarker and potential therapeutic target for LUAD. METHODS: NGEF expression data for multiple cancers and LUAD were downloaded from multiple databases. The high- and low-NGEF expression groups were constructed based on median NGEF expression in LUAD samples, and then performed Kaplan-Meier survival analysis. Differentially expressed genes (DEGs) from the two NGEF expression groups were screened and applied to construct a protein-protein interaction network. The primary pathways were obtained using gene set enrichment analysis. The associations between NGEF expression and clinical characteristics, immune infiltration, immune checkpoint inhibitors (ICIs), sensitivity to chemotherapy, and tumor mutation burden (TMB) were investigated using R. Levels of NGEF expression in the lung tissue was validated using single-cell RNA sequencing, quantitative polymerase chain reaction (qPCR), immunohistochemical staining, and western blot analysis. RESULTS: The expression of NGEF mRNA was upregulated in multiple cancers. mRNA and protein expression levels of NGEF were higher in patients with LUAD than in controls, as validated using qPCR and western blot. High NGEF expression was an independent prognostic factor for LUAD and was associated with advanced tumor stage, large tumor size, more lymph node metastasis, and worse overall survival (OS). A total of 182 overlapping DEGs were screened between The Cancer Genome Atlas and GSE31210, among which the top 20 hub genes were identified. NGEF expression was mainly enriched in the pathways of apoptosis, cell cycle, and DNA replication. Moreover, elevated NGEF expression were associated with a high fraction of activated memory CD4+ T cells and M0 macrophages; elevated expression levels of the ICIs: programmed cell death 1 and programmed cell death 1 ligand 1 expression; higher TMB; and better sensitivity to bortezomib, docetaxel, paclitaxel, and parthenolide, but less sensitivity to axitinib and metformin. CONCLUSION: NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Fatores de Troca do Nucleotídeo Guanina , Imunoterapia , Neoplasias Pulmonares , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Prognóstico , Mapas de Interação de Proteínas
12.
Chem Asian J ; : e202400443, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773630

RESUMO

Two polyhedral silver-thiolate clusters, [S@Ag16(Tab)10(MeCN)8](PF6)14 (Ag16) and [Ag12(Tab)6(DMF)12](PF6)12 (Ag12), were synthesized by using electroneutral Tab species as protective ligands (Tab=4-(trimethylammonio)benzenethiolate, DMF=N,N-dimethylformamide, MeCN=acetonitrile). Ag16 has a decahedral shape composed of eight pentagon {Ag5} units and two square {Ag4} units. The structure of Ag12 is a cuboctahedron, a classical Archimedean structure composed of six triangular faces and eight square faces. The former configuration is discovered in silver-thiolate cluster for the first time, possibly benefited from the more flexible coordination between the Tab ligand and Ag+ facilitated by the electropositive -N(CH3)3 + substituent group. Third-order nonlinear optical studies show that both clusters in DMF exhibit reverse saturate absorption response under the irradiation of 532 nm laser.

13.
Nat Prod Res ; : 1-7, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785383

RESUMO

Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1ß, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.

14.
J Asian Nat Prod Res ; 26(8): 883-891, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38602500

RESUMO

Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.


Assuntos
Antifúngicos , Candida albicans , Óxido Nítrico , Triterpenos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Camundongos , Animais , Estrutura Molecular , Candida albicans/efeitos dos fármacos , Células RAW 264.7 , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Folhas de Planta/química , Testes de Sensibilidade Microbiana , Lipopolissacarídeos/farmacologia , Meliaceae/química , Caules de Planta/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação
15.
Dig Dis Sci ; 69(6): 2109-2122, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38564148

RESUMO

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.


Assuntos
Doença do Armazenamento de Colesterol Éster , Heterozigoto , Linhagem , Esterol Esterase , Humanos , Masculino , Feminino , Doença do Armazenamento de Colesterol Éster/genética , Doença do Armazenamento de Colesterol Éster/diagnóstico , Esterol Esterase/genética , Adulto , Mutação , Genes Dominantes , Pessoa de Meia-Idade , Fenótipo , Adolescente , Criança
16.
Sci Rep ; 14(1): 9679, 2024 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678045

RESUMO

Citri Reticulatae Pericarpium is a traditional Chinese medicine with extremely high health benefits as well as clinical value. In vivo and in vitro tests have proved that its main active secondary metabolites are flavonoids. However, they have not been comprehensively analyzed up to now mainly due to lack of suitable analysis method. To solve this problem, a novel strategy based on precursor ions locked and targeted MS/MS analysis was proposed. Firstly, the database of the flavonoids previously isolated from Citri Reticulatae Pericarpium was established to obtain the characteristics of their precursor ions. Secondly, after performing the full MS scan of the extract, all compounds in the total ion chromatogram were extracted by Compound Discoverer software. Thirdly, the precursor ions of the flavonoids were locked from the extracted compounds according to their characteristics, forming a precursor ions list. Finally, the precursor ions in the constructed list were performed targeted MS/MS analysis for structures characterization. As a result, total 187 flavonoids were successfully identified, and except for flavones, flavonols as well as dihydroflavones, some chalcones were also characterized from Citri Reticulatae Pericarpium for the first time.


Assuntos
Citrus , Flavonoides , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Flavonoides/análise , Flavonoides/química , Citrus/química , Íons , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise
17.
Sci Rep ; 14(1): 9493, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664527

RESUMO

The symptoms of tracheobronchial foreign body in the elderly are not typical, so they are often missed or misdiagnosed. This study aims to depict the clinical characteristics of tracheobronchial foreign body inhalation in the elderly. We retrospectively analysed the clinical data of elder patients (age ≥ 65 years) diagnosed with tracheal and bronchial foreign bodies. The data included age, sex, clinical symptoms, type and location of foreign bodies, prehospital duration, Chest CT, bronchoscopic findings, and frequencies and tools for removing these elderly patients' tracheal and bronchial foreign bodies. All patients were followed up for a half year. Fifty-nine cases were included, of which only 32.2% had a definite aspiration history. Disease duration > 30 days accounted for 27.1% of the patients. 27.1% of the patients had a history of stroke, and 23.8% had Alzheimer's Disease. Regarding clinical symptoms, patients mainly experience cough and expectoration. The most common CT findings were abnormal density shadow (37.3%) and pulmonary infiltration (22.0%). Under bronchoscopy, purulent secretions were observed in 52.5% of patients, and granulation tissue hyperplasia was observed in 45.8%. Food (55.9%) was the most common foreign object, including seafood shells (5.1%), bones (20.3%), dentures (18.6%), and tablets (20.3%). The success rate of foreign body removal under a bronchoscope was 96.7%, 28.8% of the foreign bodies were on the left and 69.5% on the right. 5.1% of the elderly patients required rigid bronchoscopy, and 6.8% required two bronchoscopies. In elderly cohorts, tracheal foreign bodies are obscured by nonspecific clinical presentations and a paucity of aspiration history, challenging timely diagnosis. Predominantly constituted by food particles, with a notable predilection for the left bronchial tree, these cases demand skilled bronchoscopic management, occasionally requiring sophisticated approaches for successful extraction.


Assuntos
Brônquios , Broncoscopia , Corpos Estranhos , Traqueia , Humanos , Corpos Estranhos/cirurgia , Corpos Estranhos/diagnóstico , Corpos Estranhos/diagnóstico por imagem , Idoso , Masculino , Feminino , Brônquios/diagnóstico por imagem , Brônquios/patologia , Traqueia/diagnóstico por imagem , Broncoscopia/métodos , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Fitoterapia ; 175: 105961, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626855

RESUMO

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC50 value of 8.15 ± 0.20 µM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase.


Assuntos
Antineoplásicos Fitogênicos , Medicina Tradicional Tibetana , Compostos Fitoquímicos , Raízes de Plantas , Rubia , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Estrutura Molecular , Linhagem Celular Tumoral , Rubia/química , Raízes de Plantas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Antraquinonas/farmacologia , Antraquinonas/isolamento & purificação , Antraquinonas/química , Tibet , Quinonas/farmacologia , Quinonas/isolamento & purificação , Quinonas/química
19.
Ann Hematol ; 103(5): 1765-1774, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38509388

RESUMO

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.


Assuntos
Doença de Gaucher , Esplenopatias , Adulto , Humanos , Masculino , Doença de Gaucher/complicações , Doença de Gaucher/genética , Doença de Gaucher/cirurgia , Esplenectomia , Medula Óssea , Fenótipo , Esplenomegalia/genética , Mutação , Glucosilceramidase/genética
20.
Curr Med Sci ; 44(2): 281-290, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453792

RESUMO

Recent studies have shown that cellular levels of polyamines (PAs) are significantly altered in neurodegenerative diseases. Evidence from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress, mitochondrial metabolism, cellular immunity, and ion channel functions. Dysfunction of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative diseases. Therefore, in the current work, evidence was collected to determine the possible associations between cellular levels of PAs, and related enzymes and the development of several neurodegenerative diseases, which could provide a new idea for the treatment of neurodegenerative diseases in the future.


Assuntos
Doenças Neurodegenerativas , Poliaminas , Animais , Poliaminas/metabolismo , Estresse Oxidativo , Mitocôndrias/metabolismo , Apoptose , Doenças Neurodegenerativas/metabolismo
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