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1.
Nanotechnology ; 34(46)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37499636

RESUMO

To obtain a magnetically separable, low-cost and highly efficient reduction catalyst, microbial carbon-loaded bimetallic palladium/iron nanoparticles (MC-FePd3NPs) were synthesized in this study by using waste yeast residue doped with iron during the preparation process of microbial carbon-loaded monometallic palladium nanoparticles (MC-Pd NPs). The morphology, crystal structure, magnetic properties and catalytic performance of MC-FePd3NPs for the reduction ofp-nitrophenol (p-NP) were investigated by various characterization techniques, such as SEM-EDS, TEM, XRD, PPMS-9 and UV-vis spectroscopy. The catalytic experiments showed that the MC-FePd3NPs prepared under pyrolysis conditions at 700 °C had an apparent rate constant of 1.85 × 10-1s-1which is better than the rate constants of MC-Pd NPs and other palladium-based nanocatalytic materials reported so far. The amount of palladium used in the synthesis of MC-FePd3NPs was half that of MC-Pd NPs. The catalyst exhibited soft magnetic ordering behavior and still showed a catalytic efficiency of 97.4% after five consecutive reaction cycles. Furthermore, employing MC-FePd3NPs reduces the costs of catalyst preparation and use in production. MC-FePd3NPs with efficient catalytic properties, facile magnetic separation and recyclability, and low costs of preparation and use have considerable potential for industrial applications.

2.
Indian J Microbiol ; 63(3): 324-336, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37781006

RESUMO

Members of the plant mycobiota are all associated to varying degrees with the development of plant diseases. Although many reports on the plant mycobiota are well documented, the relationships between mycobiota of Rosa roxburghii and plant diseases are poorly understood. Mutual interactions and extent of the roles of microbial communities associated with R. roxburghii and the source of pathogens are still unclear, and more research is needed on the health benefits of this ecologically important population. Using high-throughput sequencing, we analyzed the mycobiota composition and ecological guilds of the rhizosphere, root, and phyllosphere of healthy and diseased R. roxburghii from the Tianfu R. roxburghii Industrial Park in Panzhou city, Guizhou province. Analysis of community composition showed that the relative abundance of pathogens of leaf spot, including Alternaria, Pestalotiopsis and Neofusicoccum in the phyllosphere of diseased plant (LD), were 1.15%, 0.15% and 0.06%, and the relative abundance of Alternaria and Pestalotiopsis were 0.96% and 0.58% in healthy plant (LH). The alpha diversity indices indicated that fungal diversity was higher in healthy plants compared to diseased plants in each compartment. The alpha diversity index of fungi in the phyllosphere (LH) of healthy R. roxburghii, including Shannon, Chao-1, and Faith-pd indices, was 1.02, 81.50 and 10.42 higher than that of the diseased (LD), respectively. The fungi in the rhizosphere of healthy was 1.03, 59.00 and 5.56 higher than the diseased, respectively. The Shannon index of fungi in the root of healthy was 0.29 higher than that of diseased. Principal Coordinate analysis and ANOSIM results showed that there were significant differences in mycobiota composition between healthy and diseased phyllospheres (P < 0.05), as well as rhizosphere fungal community, while there was no significant difference between healthy and diseased roots (P > 0.05). Linear discriminant analysis effect size revealed that, at different taxonomic levels, there were significantly different taxa between the healthy and diseased plants in each compartment. The ecological guilds differed between healthy and diseased plants according to the FUNGuild analysis. For example, of healthy compared to diseased plants, the percentages of "lichenized-undefined saprotroph" were increased by 2.34%, 0.44%, and 1.54% in the phyllosphere, root, and rhizosphere, respectively. In addition, the plant pathogens existed in each compartment of R. roxburghii, but the percentages of "plant pathogen" were increased by 1.16% in the phyllosphere of diseased compared to healthy plants. Together, the ecological guild and co-occurrence network indicated that the potential pathogens of leaf spot were mainly found in the phyllosphere. This study explained one of pathogen origin of leaf spots of R. roxburghii by the microbial community ecology, which will provide the new insights for identification of plant pathogens.

3.
Lab Invest ; 102(10): 1088-1100, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35690649

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease in which nucleotide-binding domain of leucine-rich repeat protein 3 (NLRP3) inflammasome plays an important role. The present research was aimed to explore the protective function of ADAR1, an RNA editing enzyme, against inflammatory damages in high-fat diet (HFD)-induced NAFLD through inhibiting NLRP3 inflammasome and subsequent inflammation. A total of 30 patients with NAFLD were investigated, and ADAR1 mRNA expression in peripheral blood monocytes surveyed. The in vivo study used lentivirus to explore the function of ADAR1 overexpression in the HFD-induced mouse model of NAFLD. The in vitro study used lentivirus and siRNA to explore the function of ADAR1 on the NLRP3 inflammasome activation in THP-1 cells. Results shown that the ADAR1 expression was upregulated in NAFLD patients in comparison to healthy controls. In vivo, the upregulation of ADAR1 impaired NLRP3 inflammasome activation and alleviated liver disease in HFD mice in comparison to the control group. Moreover, ADAR1 overexpression attenuated NLRP3 inflammasome in lipopolysaccharide (LPS)+ palmitic acid (PA)-induced THP-1 cells, while ADAR1 knockdown increased the NLRP3 inflammasome activation. Furthermore, we speculated that c-Jun may participate in ADAR1's inhibition of NLRP3 inflammasome. Our results suggested that ADAR1 is a potential treatment target for NAFLD via regulating the activation of NLRP3 inflammasome.


Assuntos
Adenosina Desaminase/metabolismo , Inflamassomos , Hepatopatia Gordurosa não Alcoólica , Adenosina Desaminase/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Nucleotídeos/metabolismo , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo
4.
Ann Hum Genet ; 83(2): 95-99, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30276801

RESUMO

Dilated cardiomyopathy (DCM) is a relatively frequent myocardial disease that may lead to heart failure, syncope, and sudden cardiac death. Genetic factors play important roles in the etiology of the disease. To date, at least 50 genes have been identified in patients with DCM, among them, only three mutations have been reported in Synemin (SYNM) gene. In this study, we investigate a Chinese family of three generations with four patients with DCM. Employing whole-exome sequencing (WES) and bioinformatics strategies, a novel heterozygous missense mutation p.(Trp538Arg) of SYNM was identified and cosegregated with the affected family members. The missense mutation locates in the C-terminal domain of SYNM and leads to a substitution of tryptophan by arginine and may cause the structure change of synemin protein. In conclusion, we employed WES to detect the mutations of DCM patients and identified a novel likely pathogenic mutation in SYNM gene. Our study not only expands the spectrum of SYNM mutations, it further confirms that mutations in SYMN may underlie nonfamilial DCM, and offers genetic testing information to additional DCM patients.


Assuntos
Cardiomiopatia Dilatada/genética , Proteínas de Filamentos Intermediários/genética , Adolescente , Adulto , Povo Asiático/genética , China , Feminino , Heterozigoto , Humanos , Masculino , Mutação de Sentido Incorreto , Linhagem , Sequenciamento do Exoma
5.
Medicine (Baltimore) ; 103(2): e36926, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38215088

RESUMO

RATIONALE: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignant primary hepatic lymphoma. The sensible choice of treatment for patients with primary lymphoma combined with atrial fibrillation (AF) is controversial and challenging. PATIENT CONCERNS: The patient presented with both primary hepatic MALT lymphoma and AF, which was difficult to manage. DIAGNOSES: Pathological and immunohistochemical examination are helpful for definitive diagnosis. INTERVENTIONS: Surgical resection and subsequent anticoagulant therapy are main treatment methods, and adjuvant therapy depends on the situation. OUTCOMES: Primary hepatic MALT lymphoma is easy to misdiagnosis due to a lack of typical symptoms and imaging signs. LESSONS: This case highlights for patients with primary hepatic MALT lymphoma combined with AF, toxicity caused by adjuvant chemotherapy should be fully considered, and careful selection should be made based on the general conditions and complications of patients.


Assuntos
Fibrilação Atrial , Linfoma de Zona Marginal Tipo Células B , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Fibrilação Atrial/complicações
6.
Ultrason Sonochem ; 107: 106933, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38865900

RESUMO

Extraction of anthocyanins from Lycium ruthenicum Murr. (L. ruthenicum) is a notable challenge in food production, requiring methods that balance efficiency and safety. In this study, we conducted a comparative analysis the extraction of anthocyanins by natural air drying (NAD), vacuum freeze drying (VFD), hot air drying (HAD), and vacuum microwave drying (MVD) combined with ultrasonic-assisted enzymolysis extraction (UAEE). The results demonstrated that the extraction yield and antioxidant activity of anthocyanins were significantly higher in VFD. This phenomenon can be attributed to the modification of raw material's microstructure, leading to an increased extraction yield of specific anthocyanins such as Cyanidin-3-galactoside, Delphinidin chloride, Cyanidin, and Petunidin. According to the pretreatment results, the extraction process of anthocyanins was further optimized. The highest yield (3.16 g/100 g) was obtained in following conditions: 0.24 % pectinase, 48 °C, solid:liquid = 1:21, and 21 min ultrasonic time. This study improves the commercial value and potential application of L. ruthenicum in food industry.


Assuntos
Antocianinas , Dessecação , Lycium , Antocianinas/isolamento & purificação , Antocianinas/química , Lycium/química , Dessecação/métodos , Ondas Ultrassônicas , Fracionamento Químico/métodos , Antioxidantes/isolamento & purificação , Antioxidantes/química , Poligalacturonase , Micro-Ondas
7.
Front Med ; 18(1): 180-191, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37776435

RESUMO

Lipin proteins including Lipin 1-3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

8.
Food Chem X ; 22: 101357, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38623517

RESUMO

The combination of pretreatment and vacuum freeze-drying (VFD) technology is an effective technique for extending the shelf life of apricots, reducing costs and energy consumption. However, the impact of pretreatment on the freeze-drying and quality characteristics of apricots is still unclear. The effects of ultrasound (US), freeze-thaw (FT), and their combination (FT-US) on water migration and quality characteristics of apricot slices on VFD were studied. LR-NMR and SEM showed that pretreatment significantly reduced the time (19.05%-33.33%) and energy consumption (17.67%-35.66%) of the VFD process. Compared with the control group, the US, FT, and FT-US improved the color, texture, rehydration ability, and flavor of apricot slices. Among them, FT-US retained the most biologically active substances and antioxidant capacity, with the highest sensory score. Overall, FT-US pretreatment induced changes in the microstructure and chemistry of apricots, which contributed to the production of high-quality VFD apricot slices.

9.
Heliyon ; 10(7): e28674, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571653

RESUMO

Paroxysmal kinesigenic dyskinesia (PKD) represents the most prevalent form of paroxysmal dyskinesia, characterized by recurrent and transient attacks of involuntary movements triggered by a sudden voluntary action. In this study, whole-exome sequencing was conducted on a cohort of Chinese patients to identify causal mutations. In one young female case, a de novo CACNA1B variant (NM_000718.3:exon3:c.479C > T:p.S160F) was identified as the causative lesion. This finding may broaden the phenotypic spectrum of CACNA1B mutations and provide a prospective cause of primary PKD. Additionally, a novel start-loss variant (NM_000682.7:c.3G > A) within ADRA2B further denied its association with benign adult familial myoclonic epilepsy, and a KCNQ2 E515D variant that was reported as a genetic susceptibility factor for seizures had no damaging effect in this family. In sum, this study established a correlation between CACNA1B and primary PKD, and found valid evidence that further negates the pathogenic role of ADRA2B in benign adult familial myoclonic epilepsy.

10.
Medicine (Baltimore) ; 103(11): e37484, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489730

RESUMO

Colorectal cancer (CRC) is one of the most prevalent types of malignant tumors. It's vital to explore new biomarkers and potential therapeutic targets in CRC lung metastasis through adopting integrated bioinformatics tools. Multiple cohort datasets and databases were integrated to clarify and verify potential key candidate biomarkers and signal transduction pathways in CRC lung metastasis. DAVID, STRING, UALCAN, GEPIA, TIMER, cBioPortal, THE HUMAN PROTEIN ATLAS, GSEA 4.3.2, FUNRICH 3.1.3, and R 4.2.3 were utilized in this study. The enriched biological processes and pathways modulated by the differentially expressed genes (DEGs) were determined with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. The search tool Retrieval of Interacting Genes and Cytoscape were used to construct a protein-protein interaction network among DEGs. Four hundred fifty-nine colorectal primary cancer and lung metastatic gene expression profiles were screened from 3 gene expression profiles (GSE41258, GSE68468, and GSE41568). Forty-one upregulated genes and 8 downregulated genes were identified from these 3 gene expression profiles and verified by the transcriptional levels of hub genes in other GEO datasets and The Cancer Genome Atlas database. Two pathways (immune responses and chemokine receptors bind chemokines), 13 key DEGs, 6 hub genes (MMP3, SFTPD, ABCA3, CLU, APOE, and SPP1), and 2 biomarkers (APOE, SPP1) with significantly prognostic values were screened. Forty-nine DEGs were identified as potential candidate diagnostic biomarkers for patients with CRC lung metastasis in present study. Enrichment analysis indicated that immune responses and chemokine receptors bind chemokines may play a leading role in lung metastasis of CRC, and further studies are needed to validate these findings.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Humanos , Prognóstico , Perfilação da Expressão Gênica , Biomarcadores , Neoplasias Pulmonares/genética , Neoplasias Colorretais/genética , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Quimiocinas/metabolismo , Apolipoproteínas E/genética , Biologia Computacional , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica
11.
Int Immunopharmacol ; 130: 111754, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38428147

RESUMO

Acute kidney injury (AKI) is a complex disease, with macrophages playing a vital role in its progression. However, the mechanism of macrophage function remains unclear and strategies targeting macrophages in AKI are controversial. To address this issue, we used single-cell RNA-seq analysis to identify macrophage sub-types involved in ischemia-reperfusion-induced AKI, and then screened for associated hub genes using intersecting bulk RNA-seq data. The single-cell and bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) database. Screening of differentially-expressed genes (DEGs) and pseudo-bulk DEG analyses were used to identify common hub genes. Pseudotime and trajectory analyses were performed to investigate the progression of cell differentiation. CellChat analysis was performed to reveal the crosstalk between cell clusters. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify enriched pathways in the cell clusters. Immunofluorescence and RT-PCR were preformed to validate the expression of the identified hub genes. Four hub genes, Vim, S100a6, Ier3, and Ccr1, were identified in the infiltrated macrophages between normal samples and those 3 days after ischemia-reperfusion renal injury (IRI); all were associated with the progression of IRI-induced AKI. Increased expression of Vim, S100a6, Ier3, and Ccr1 in infiltrated macrophages may be associated with inflammatory responses and may mediate crosstalk between macrophages and renal tubular epithelial cells under IRI conditions. Our results reveal that Ier3 may be critical in AKI, and that Vim, S100a6, Ier3, and Ccr1 may act as novel biomarkers and potential therapeutic targets for IRI-induced AKI.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Humanos , RNA-Seq , Análise da Expressão Gênica de Célula Única , Injúria Renal Aguda/genética , Traumatismo por Reperfusão/genética , Rim , Macrófagos , Isquemia
12.
Mitochondrion ; 75: 101851, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336146

RESUMO

Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.


Assuntos
Injúria Renal Aguda , Doenças Mitocondriais , Humanos , Camundongos , Animais , Cisplatino/efeitos adversos , Apoptose , Injúria Renal Aguda/induzido quimicamente , Rim/metabolismo , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Proteínas de Transporte , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo
13.
Food Chem X ; 22: 101361, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38633738

RESUMO

The changes in the qualities and sweet-substance levels of Junzao jujube during variable-temperature drying (VTD) were investigated. The results showed that VTD retains the original color of jujube, reduces its hardness and chewiness, and decreases its wrinkling while shortening the drying time by 13.2% compared with that of constant temperature drying (CTD). "Electronic-tongue" taste analysis showed that the sweetness of VTD jujube is significantly higher than that for CTD. This is shown to be related to the contents of sucrose, fructose, and glucose, as well as the activities of invertase and sucrose synthase enzymes. In addition, the content trends for sweet amino acids are correlated with the temperature gradient used in VTD. Thus, the present study elucidates the factors governing the transformation of sugar substances in jujube during VTD, as well as providing a practical reference for the application of VTD in the jujube industry.

14.
Open Forum Infect Dis ; 11(5): ofae241, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38756766

RESUMO

Background: Pregnant women with chronic hepatitis B (CHB) exhibit unique clinical features in terms of postpartum immune system reconstitution and recovery from pregnancy-related changes. However, current studies focus primarily on the outcomes of maternal-infant transmission and postpartum hepatitis flares. We aimed to evaluate the profiles of hepatitis B core-related antigen (HBcrAg) and pregenomic RNA (pgRNA) in pregnant women with CHB. Methods: This retrospective analysis included treatment-naïve pregnant women with CHB who were followed up regularly in an outpatient clinic from 2014 to 2021. Baseline HBcrAg and pgRNA levels were compared in patients with different disease phases. Changes in these parameters were examined in a subset of patients receiving antiviral prophylaxis. HBcrAg and pgRNA levels were measured before treatment, at 32 weeks of gestation, and postpartum. Results: The final analysis included a total of 121 patients, 100 of whom were hepatitis B e antigen (HBeAg)-positive (96 and 4 in the immune-tolerant and -indeterminate phases, respectively) and 21 of whom were HBeAg-negative (6 and 15 in the immune-active and -inactive carrier phases, respectively). The HBeAg-negative group vs the HBeAg-positive group had lower levels of baseline HBcrAg (median [interquartile range {IQR}], 3.7 [3.0-5.9] vs 8.6 [8.4-8.7] log10 U/mL; P < .01) and pgRNA (median [IQR], 0.0 [0.0-2.5] vs 7.8 [7.6-8.1] log10 copies/mL; P < .01). The serum levels of HBcrAg and pgRNA were highest in immune-tolerant carriers and lowest in immune-inactive carriers. In HBeAg-positive patients, the correlation coefficients of HBcrAg and pgRNA with hepatitis B virus (HBV) DNA were 0.40 and 0.43, respectively; in HBeAg-negative patients, they were 0.53 and 0.51, respectively (all P < .05). The correlation coefficients with hepatitis B surface antigen (HBsAg) were 0.55 and 0.52 (P < .05) in HBeAg-positive patients, respectively, while in HBeAg-negative patients they were 0.42 and 0.37, respectively (P > .05). Among 96 patients receiving antiviral prophylaxis, we detected a rapid decrease in HBV DNA to an undetectable level during treatment but relatively stable levels of pgRNA and HBcrAg. Conclusions: HBcrAg and pgRNA levels are lower in HBeAg-negative patients than in HBeAg-positive patients. These 2 markers are significantly associated with HBV DNA irrespective of HBeAg status, while they are significantly associated with HBsAg only in HBeAg-positive patients.

15.
16.
Mol Biomed ; 5(1): 24, 2024 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937317

RESUMO

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.


Assuntos
Progressão da Doença , Fibrose , Perfilação da Expressão Gênica , Insuficiência Renal Crônica , Análise de Célula Única , Animais , Camundongos , Fibrose/patologia , Fibrose/metabolismo , Fibrose/genética , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Rim/patologia , Rim/metabolismo , Transcriptoma , Espécies Reativas de Oxigênio/metabolismo , Transição Epitelial-Mesenquimal/genética , Modelos Animais de Doenças , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/genética
17.
Mol Genet Genomic Med ; 12(8): e2503, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39140707

RESUMO

BACKGROUND: The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. METHODS: This study included 226 migraineurs and 452 age- and sex-matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP-SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. RESULTS: The RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [ORadj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068-2.281)]. One significant two-way SNP-SNP interaction was found (PRKCA rs2228945-BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. CONCLUSIONS: This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk.


Assuntos
Transtornos de Enxaqueca , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-akt , Humanos , Transtornos de Enxaqueca/genética , Feminino , Masculino , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Transdução de Sinais/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Pessoa de Meia-Idade
18.
Laryngoscope Investig Otolaryngol ; 8(6): 1484-1499, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38130248

RESUMO

Objectives: To compare the deposition patterns within the nasal cavity between the bi-directional and unilateral nasal delivery systems. And to summarize the clinical application of the bi-directional nasal drug delivery devices. Data source: PubMed, Cochrane Library, Embase, and Web of Science databases. Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We included studies exploring patterns and influencing factors of particle depositions within the nasal cavity among patients, healthy controls, and nose cast models using the bi-directional and unilateral nasal delivery system. The clinical application of the bi-directional delivery devices was also summarized. Results: A total of 24 studies were included in this review. Bi-directional nasal delivery systems utilize forced exhalation to power the delivery of drugs to deeper areas of the nasal cavity and paranasal sinuses. Unilateral nasal delivery systems included traditional liquid spray pumps, the aerosol mask system, nebulization, and conventional nasal inhalation. Compared with unilateral delivery systems, the bi-directional nasal delivery system provided a more extensive and efficient nasal deposition in the nasal cavity, especially in the olfactory cleft, without lung deposition. Several parameters, including particle size, pulsatile flow, and nasal geometry, could significantly influence nasal deposition. The bi-directional nasal delivery system enables better delivery of steroids or sumatriptan to the sinonasal cavity's high and deep target sites. This bi-directional delivery device demonstrated an effective and well-tolerated treatment that produced high drug utilization, rapid absorption, and sustained symptom improvement among patients with chronic rhinosinusitis (CRS) or migraine. Conclusion: The bi-directional nasal drug delivery systems demonstrated significantly higher drug deposition in superior and posterior regions of the nasal cavity than unilateral nasal delivery systems. Further studies should explore its potential role in delivering drugs to the olfactory cleft among patients with olfactory disorders and central nervous system diseases. Level of evidence: N/A.

19.
Acta Otolaryngol ; 143(10): 887-893, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37991166

RESUMO

BACKGROUND: The odor identification test is culture-dependent. OBJECTIVES: This study aimed to develop a culturally adapted version of the 5-item Quick olfactory Sniffin' Sticks Test (Q-Stick) to adapt to the clinical environment in China. METHODS: The study included 3 phases: (1) develop a culturally adapted version of Q-Stick by replacing unfamiliar odors in the original Q-Stick test (N = 344); (2) validate the culturally adapted version of Q-Stick against two widely used olfactory tests: the Sniffin' Sticks olfactory test and the 12-item Cross-Cultural Smell Identification Test (CC-SIT) (N = 286); 3) evaluate the test-retest reliability of the culturally adapted version of Q-Stick (N = 60). RESULTS: After modification of the interference items, the correct recognition rate of leather was changed from 54.65% to 90.00%. The adapted version of the Q-Stick score significantly correlated with both the Sniffin' Sticks score (r = 0.7642, p < .0001) and CC-SIT score (r = 0.7403, p < .0001). Normal olfaction is indicated if the culturally adapted version of the Q-Stick score > 4 (specificity 70.00%, sensitivity 83.33%, Youden index 0.533) and Q-Stick score ≤ 4 indicates olfactory dysfunction. The 3-month test-retest reliability coefficient was as high as 0.96. CONCLUSIONS AND SIGNIFICANCE: The culturally adapted version of Q-Stick is an effective and stable screening tool to identify patients with olfactory dysfunction in China.


Assuntos
Transtornos do Olfato , Olfato , Humanos , Transtornos do Olfato/diagnóstico , Reprodutibilidade dos Testes , Limiar Sensorial , China
20.
J Int Med Res ; 51(12): 3000605231220825, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38156408

RESUMO

OBJECTIVE: Malignant biliary obstruction (MBO) is a rare disease with a poor prognosis. Recent studies have shown that endoscopic radiofrequency ablation (ERFA) may improve survival. We conducted a systematic review and meta-analysis of the efficacy of ERFA in combination with biliary stent placement for the treatment of MBO. METHODS: The study was registered in INPLASY (number 202340096). The PubMed, Cochrane Library, Web of Science, and Embase databases were searched from inception to April 2023. We selected studies comparing the efficacy of ERFA plus stent placement with stent placement alone. The primary outcomes were pooled hazard ratios (HRs) for overall survival and stent patency; the secondary outcomes were the odds ratios (ORs) for adverse events. RESULTS: Eleven studies (four randomized controlled trials and seven observational studies) were included in the meta-analysis. Pooled analysis showed a difference in survival time between the two groups (HR 0.65, 95% confidence interval [CI] 0.58-0.73, I2 = 40%). However, there were no differences in the duration of stent patency or the incidence of adverse events (HR 1.04, 95% CI 0.84-1.29, I2 = 46%; OR 1.41, 95% CI 1.02-1.96, I2 = 29%). CONCLUSIONS: ERFA has a significant survival benefit for MBO, but does not increase the risk of adverse events.


Assuntos
Neoplasias dos Ductos Biliares , Colestase , Ablação por Radiofrequência , Stents , Humanos , Neoplasias dos Ductos Biliares/cirurgia , Colestase/etiologia , Colestase/cirurgia , Endoscopia , Resultado do Tratamento
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