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1.
Heliyon ; 10(18): e37086, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39315218

RESUMO

Background: AGBL2's role in tumorigenesis and cancer progression has been reported in several cancer studies, and it is closely associated with α-tubulin detyrosination. The roles of AGBL2 and α-tubulin detyrosination in renal cell carcinoma (RCC) pathogenesis remain unclear and require further investigation. Methods: In this study, we conducted an analysis of AGBL2 expression differences between renal clear cell carcinoma tissues and normal tissues using data from The Cancer Genome Atlas (TCGA). We performed a comprehensive prognostic analysis of AGBL2 in Kidney Renal Clear Cell Carcinoma (KIRC) using univariate and multivariate Cox regression. Based on the results of the Cox analysis, we constructed a prognostic model to assess its predictive capabilities. Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of AGBL2 in renal cancer. We conducted further validation by analyzing cancer tissue samples and renal cancer cell lines, which confirmed the role of AGBL2 in promoting RCC cell proliferation and migration through in vitro experiments. Additionally, we verified the impact of AGBL2's detyrosination on α-tubulin using the tubulin carboxypeptidase (TCP) inhibitor parthenolide. Finally, we performed sequencing analysis on AGBL2 knockdown 786-O cells to investigate the correlation between AGBL2, immune infiltration, and AKT phosphorylation. Moreover, we experimentally demonstrated the enhancing effect of AGBL2 on AKT phosphorylation. Results: TCGA analysis revealed a significant increase in AGBL2 expression in RCC patients, which was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). According to the analysis results, we constructed column-line plots to predict the 1-, 3-, and 5-year survival outcomes in RCC patients. Additionally, the calibration plots assessing the model's performance exhibited favorable agreement with the predicted outcomes. And the ROC curves showed that AGBL2 showed good diagnostic performance in KIRC (AUC = 0.836)). Cell phenotyping assays revealed that AGBL2 knockdown in RCC cells significantly inhibited cell proliferation and migration. Conversely, overexpression of AGBL2 resulted in increased cell proliferation and migration in RCC cells. We observed that AGBL2 is predominantly located in the nucleus and can elevate the detyrosination level of α-tubulin in RCC cells. Moreover, the enhancement of RCC cell proliferation and migration by AGBL2 was partially inhibited after treatment with the TCP inhibitor parthenolide. Analysis of the sequencing data revealed that AGBL2 is associated with a diverse array of biological processes, encompassing signal transduction and immune infiltration. Interestingly, AGBL2 expression exhibited a negative correlation with the majority of immune cell infiltrations. Additionally, AGBL2 was found to enhance the phosphorylation of AKT in RCC cells. Conclusion: Our study suggests that AGBL2 fosters RCC cell proliferation and migration by enhancing α-tubulin detyrosination. Moreover, elevated AGBL2 expression increases phosphorylation of AKT in RCC cells.

2.
Mol Med ; 30(1): 130, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39182021

RESUMO

BACKGROUND: Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear. METHODS: Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics. RESULTS: ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect. CONCLUSION: ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification.


Assuntos
Acetatos , Antibacterianos , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Calcificação Vascular , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Calcificação Vascular/metabolismo , Calcificação Vascular/etiologia , Calcificação Vascular/tratamento farmacológico , Camundongos , Ácidos Graxos Voláteis/metabolismo , Acetatos/farmacologia , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Masculino , Osteogênese/efeitos dos fármacos , RNA Ribossômico 16S/genética , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Vancomicina/efeitos adversos , Vancomicina/farmacologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos dos fármacos
3.
Cell Mol Biol Lett ; 29(1): 109, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143552

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported. METHODS: Candidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3. RESULTS: CircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide. CONCLUSIONS: METTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.


Assuntos
Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Metiltransferases , Neoplasias da Próstata , RNA Circular , Masculino , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Animais , Metiltransferases/metabolismo , Metiltransferases/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Movimento Celular/genética , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Feniltioidantoína/farmacologia , Feniltioidantoína/análogos & derivados , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Endogâmicos BALB C , Benzamidas , Nitrilas
4.
Ecol Evol ; 14(8): e70126, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39114168

RESUMO

To study the interspecific differentiation characteristics of species originating from recent radiation, the genotyping-by-sequencing (GBS) technique was used to explore the kinship, population structure, gene flow, genetic variability, genotype-environment association and selective sweeps of Picea asperata complex with similar phenotypes from a genome-wide perspective. The following results were obtained: 14 populations of P. asperata complex could be divided into 5 clades; P. wilsonii and P. neoveitchii diverged earlier and were more distantly related to the remaining 6 spruce species. Various geological events have promoted the species differentiation of P. asperata complex. There were four instances of gene flow among P. koraiensis, P. meyeri, P. asperata, P. crassifolia and P. mongolica. The population of P. mongolica had the highest level of nucleotide diversity, and P. neoveitchii may have experienced a bottleneck recently. Genotype-environment association found that a total of 20,808 genes were related to the environmental variables, which enhanced the adaptability of spruce in different environments. Genes that were selectively swept in the P. asperata complex were primarily associated with plant stress resistance. Among them were some genes involved in plant growth and development, heat stress, circadian rhythms and flowering. In addition to the commonly selected genes, different spruce species also displayed unique genes subjected to selective sweeps that improved their adaptability to different habitats. Understanding the interspecific gene flow and adaptive evolution of Picea species is beneficial to further understanding the species relationships of spruce and can provide a basis for studying spruce introgression and functional genomics.

5.
Transl Cancer Res ; 13(7): 3536-3555, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39145091

RESUMO

Background: The prognosis for patients with kidney renal clear cell carcinoma (KIRC) remains unfavorable, and the understanding of SRY-box transcription factor 11 (SOX11) in KIRC is still limited. The purpose of this paper is to explore the role of SOX11 in the prognosis of KIRC. Methods: We analyzed SOX11 expression in KIRC and adjacent normal tissues using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Our study aims to establish a correlation between SOX11 expression and clinical pathological features. Differentially expressed genes (DEGs) were assessed using R software. Furthermore, we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). Integration of data from the Tumor Immune Estimation Resource (TIMER) and TCGA databases allowed us to assess the association between SOX11 expression and immune infiltration in KIRC. Additionally, we analyzed the association between SOX11 gene expression and N6-methyladenosine (m6A) modification in KIRC using TCGA and GEO data. Results: Our findings revealed high SOX11 expression in KIRC, which showed a significant correlation with tumor staging and prognosis. GO/KEGG and GSEA analyses indicated that SOX11 was closely associated with sodium ion transport, synaptic vesicle circulation, and oxidative phosphorylation. Analysis of the TIMER and TCGA databases demonstrated correlations of SOX11 expression levels with the presence of CD8+ T lymphocytes, neutrophils, CD4+ T cells, as well as B cells. Moreover, both the TCGA and GEO datasets showed a substantial association between SOX11 and m6A modification-related genes, namely ZC3H13, FTO, METTL14, YTHDC1, IGF2BP1, and IGF2BP2. Conclusions: SOX11 exhibits a correlation with m6A modification and immune infiltration, suggesting its potential as a prognostic biomarker for KIRC.

6.
Small ; : e2403732, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963164

RESUMO

The construction of novel structured Prussian blue analogs (PBAs) by chemical etching has attracted the most attention to PBA derivatives with outstanding performance. In this work, the unprecedented PBA orthogonal frustums are first prepared from nanocubes through a selective chemical etching approach using trisodium citrate as an etchant. The citrate ions can chelate with nickel species from the edges/corners of NiCo-PBA nanocubes and then disintegrate NiCo-PBAs resulting in the generation of NiCo-PBA orthogonal frustums. The derived CoNi2S4/Co0.91S composites still inherit the original orthogonal frustum structure and possess outstanding supercapacitor performance. This study develops a popularized method to construct novel structured PBAs and brings inspiration for designing PBA-based electrodes with advanced electrochemical performance.

7.
Cult Health Sex ; : 1-14, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975779

RESUMO

The role played by activists' sexual orientation and gender identity in their involvement and commitment to LGBT movements is an understudied area in the Chinese context. Using identity and dramaturgical theory, this qualitative study explored how activists' work and commitment toward promoting LGBT rights and services is shaped and influenced by their identities. The study draws on data from life history interviews conducted with 20 long-time LGBT activists in Yunnan, China. The findings indicate that their sexual orientation and gender identities were, in the long run, seen as assets by the activists that shaped their work and commitment in the LGBT movement. Despite initial challenges in establishing identity-based connections with co-workers/clients, the emergence of sense of inclusiveness through recognition of activists' efforts, particularly when working with diverse gender and sexual minorities, stands out as a prominent theme in this context. This dynamic is important in bolstering the longevity of activists' commitment and building the continued momentum of LGBT movements in the region and internationally.

8.
Inorg Chem ; 63(28): 12697-12702, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38950409

RESUMO

2,2'-Bipyridyl (bpy) is widely used as a chelating unit for metal complexation but is not usually considered as a hydrogen-bonding unit. This is because the metal-free bpy units are usually in a transoid conformation, and the two nitrogen lone pairs are pointed to the opposite sides. We now report a metallomacrocycle whose three metal-free bpy units are in a cisoid conformation and are fixed in the cavity. The complexation of nickel(II) only at the salen units of the triangular bpytrisalen ligand produced this rigid and planar macrocycle. Its cavity is surrounded by hydrogen-bond acceptors (N of bpy and O of salen), and it was found that unique pentagonal prism clusters of water molecules templated by the cavity were formed in the crystal. This study has not only increased the variation of the synthetic methodologies of multinuclear complexes but has also provided the structural platform on which multiple bpy units exert hydrogen-bonding functions.

9.
Plant Physiol Biochem ; 211: 108724, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744084

RESUMO

Heavy metal pollution is a global environmental problem, and Quercus variabilis has a stronger tolerance to Cd stress than do other species. We aimed to explore the physiological response and molecular mechanisms of Q. variabilis to Cd stress. In this study, the antioxidant enzyme activities of leaves were determined, while the photosynthetic parameters of leaves were measured using Handy PEA, and ion fluxes and DEGs in the roots were investigated using noninvasive microtest technology (NMT) and RNA sequencing techniques, respectively. Cd stress at different concentrations and for different durations affected the uptake patterns of Cd2+ and H+ by Q. variabilis and affected the photosynthetic efficiency of leaves. Moreover, there was a positive relationship between antioxidant enzyme (CAT and POD) activity and Cd concentration. Transcriptome analysis revealed that many genes, including genes related to the cell wall, glutathione metabolism, ion uptake and transport, were significantly upregulated in response to cadmium stress in Q. variabilis roots. WGCNA showed that these DEGs could be divided into eight modules. The turquoise and blue modules exhibited the strongest correlations, and the most significantly enriched pathways were the phytohormone signaling pathway and the phenylpropanoid biosynthesis pathway, respectively. These findings suggest that Q. variabilis can bolster plant tolerance by modulating signal transduction and increasing the synthesis of compounds, such as lignin, under Cd stress. In summary, Q. variabilis can adapt to Cd stress by increasing the activity of antioxidant enzymes, and regulating the fluxes of Cd2+ and H+ ions and the expression of Cd stress-related genes.


Assuntos
Cádmio , Regulação da Expressão Gênica de Plantas , Quercus , Estresse Fisiológico , Quercus/metabolismo , Quercus/efeitos dos fármacos , Quercus/genética , Cádmio/toxicidade , Cádmio/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Fotossíntese/efeitos dos fármacos , Antioxidantes/metabolismo
10.
BMC Plant Biol ; 24(1): 479, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816690

RESUMO

The taxonomic classification of Picea meyeri and P. mongolica has long been controversial. To investigate the genetic relatedness, evolutionary history, and population history dynamics of these species, genotyping-by-sequencing (GBS) technology was utilized to acquire whole-genome single nucleotide polymorphism (SNP) markers, which were subsequently used to assess population structure, population dynamics, and adaptive differentiation. Phylogenetic and population structural analyses at the genomic level indicated that although the ancestor of P. mongolica was a hybrid of P. meyeri and P. koraiensis, P. mongolica is an independent Picea species. Additionally, P. mongolica is more closely related to P. meyeri than to P. koraiensis, which is consistent with its geographic distribution. There were up to eight instances of interspecific and intraspecific gene flow between P. meyeri and P. mongolica. The P. meyeri and P. mongolica effective population sizes generally decreased, and Maxent modeling revealed that from the Last Glacial Maximum (LGM) to the present, their habitat areas decreased initially and then increased. However, under future climate scenarios, the habitat areas of both species were projected to decrease, especially under high-emission scenarios, which would place P. mongolica at risk of extinction and in urgent need of protection. Local adaptation has promoted differentiation between P. meyeri and P. mongolica. Genotype‒environment association analysis revealed 96,543 SNPs associated with environmental factors, mainly related to plant adaptations to moisture and temperature. Selective sweeps revealed that the selected genes among P. meyeri, P. mongolica and P. koraiensis are primarily associated in vascular plants with flowering, fruit development, and stress resistance. This research enhances our understanding of Picea species classification and provides a basis for future genetic improvement and species conservation efforts.


Assuntos
Genoma de Planta , Picea , Polimorfismo de Nucleotídeo Único , Dinâmica Populacional , Picea/genética , Filogenia , Fluxo Gênico , Adaptação Fisiológica/genética , Ecossistema
11.
Technol Health Care ; 32(S1): 351-359, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759060

RESUMO

BACKGROUND: A growing body of evidence has shown that activating spinal cord glial cells (typically astrocytes and microglial cells) is closely related to hyperpathia and persistent pain. OBJECTIVE: To investigate the expression of GFAP and CR3/CD11b in cornu dorsale medullae spinalis of rats with nonbacterial prostatitis, to explore the therapeutic efficacy and action mechanism of intrathecal injection of BNP alleviating chronic neuropathic pain. METHODS: Eighteen male SPF SD rats were randomly divided into sham operation control group, nonbacterial prostatitis group (NBP) and intrathecal injection BNP group, the NBP model was established by intraprostatic injection of CFA, and the spinal cord of L6-S1 segment was extracted seven days after intrathecal injection of BNP; The expression of GFAP and CR3/CD11b in dorsal horn of spinal cord were detected by immunofluorescence and Western blot. RESULTS: The cumulative optical density values of GFAP and CR3/CD11b immunofluorescence assay in the NBP group were higher than those in the sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.01); The expression of GFAP and CR3/CD11b in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.01). Western blot results showed that the expression of GFAP and CR3/CD11B in NBP group were higher than those in sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.05). The expression of GFAP and CR3/CD11B in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.05). CONCLUSION: Intrathecal injection of BNP can down-regulate the expressions of GFAP and CR3/CD11b in L6-S1 spinal cord of NBP rat model and to further inhibit chronic pain caused by NBP.


Assuntos
Proteína Glial Fibrilar Ácida , Peptídeo Natriurético Encefálico , Prostatite , Ratos Sprague-Dawley , Medula Espinal , Animais , Masculino , Ratos , Prostatite/metabolismo , Medula Espinal/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Injeções Espinhais , Neuralgia
12.
J Colloid Interface Sci ; 661: 614-628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38310770

RESUMO

Construction of Prussian blue analogues (PBAs) with heterostructure is beneficial to preparing PBAs derivatives with superior electrochemical performance. In this work, the core-shell nanostructured nanocubes composed of nickel hexacyanocobalt PBA (NiCo-PBA)@cobalt carbonate hydroxide (CCH) are synthesized through an in-situ epitaxial growth strategy, and the formation mechanisms of coating are carefully validated and specifically discussed. Then, the precursors are successfully transformed into hierarchical CoNi2S4/Co9S8@Co4S3 via the gas-phase vulcanization method. Benefiting from the intriguing heterostructure and multicomponent sulfides, the CoNi2S4/Co9S8@Co4S3-80 electrode exhibits a high specific capacity of 799 ± 16C/g (specific capacitance of 1595 ± 31F/g) at 1 A/g, ultra-high capacity retention of 80 % at a high current density of 20 A/g. The assembled asymmetric supercapacitor (ASC) device delivers a high energy density of 43.3 Wh kg-1 at a power density of 899 W kg-1 and exhibits superior cycling stability with the capacity retention of 88 % after 5,000 cycles. Subsequently, the fabricated all-solid-state ASC device shows an excellent energy density of 36.4 Wh kg-1 with a power density of 824 W kg-1. This work proposing rational design of combining multicomponent sulfides and core-shell heterostructure based on PBA nanocubes opens up a novel route for developing asymmetric supercapacitor electrode materials with superior performance.

13.
Aging (Albany NY) ; 16(1): 367-388, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38189809

RESUMO

BACKGROUND: Transmembrane 25(TMEM25) stands out as a potential prognostic biomarker and therapeutic target in the realm of cancer, yet its precise mechanism of action within clear cell renal cell carcinoma (ccRCC) remains unclear. MATERIALS AND METHODS: Gene expression data and clinically relevant information extracted from The Cancer Genome Atlas (TCGA) and Gene expression omnibus (GEO) databases unveil the expression patterns of TMEM25 within renal clear cell carcinoma, which reveals its prognostic and diagnostic significance. The protein expression data is available via the Human Protein Atlas (HPA) database. Further, qPCR experiments conducted on cells and tissues provide strong evidence of the gene's expression status. Additionally, they explore the correlations between TMEM25 expression and DNA methylation, gene mutations, immune cell infiltration, and drug sensitivity within this specific tumor context. RESULTS: At both the RNA and protein levels, TMEM25 displays a noteworthy downregulation in expression, which is consistently linked to an unfavorable prognosis. Receiver Operating Characteristic (ROC) curve analysis, univariate and multivariate Cox regression analyses confirmed the ability of TMEM25 to diagnose and determine prognosis in ccRCC. Its expression related closely with various immune cell types, immune checkpoints, immune inhibitors, and MHC molecules. Within ccRCC tissues, TMEM25 DNA methylation levels are observed to be elevated, and this upregulation is observed across various conditions. TMEM25 mutations also have an impact on the prognosis of ccRCC patients and the results of drug sensitivity analyses are useful for clinical decision-making. CONCLUSIONS: TMEM25 in ccRCC could potentially function as a tumor suppressor gene, holding substantial promise as a novel biomarker for diagnosing, treating, and prognosticating ccRCC patients.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Bases de Dados de Proteínas , Neoplasias Renais/genética , Biomarcadores , Prognóstico
14.
Int J Biol Macromol ; 259(Pt 1): 129197, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184048

RESUMO

Gold nanorods (AuNR) have received significant attention in tumor thermo-chemotherapy. However, insufficient thermal availability limits the in vivo highly efficient applications of AuNR in photothermal therapy. In this study, we have fabricated N-isopropylacrylamide grafted O-carboxymethyl chitosan nanoparticles (NCMC NPs) with thermo-responsive properties for co-encapsulating AuNR and doxorubicin (DOX), forming AuNR@NCMC/DOX nanocomposites (NCs). As a result of the thermo- and photothermal-responsiveness, AuNR@NCMC/DOX NCs exhibited irreversible aggregation at high temperature and under near-infrared (NIR) irradiation with an increase of size to 3 µm. When AuNR@NCMC/DOX NCs reached tumor sites following intravenous administration, they were located in the tumor vessels under NIR irradiation due to an embolization effect. This response enhanced tumor targeting, on-demand release, and the thermal performance of AuNR@NCMC/DOX NCs. We have observed higher tumor accumulation of DOX and AuNR with subsequent stronger inhibition of tumor growth than that achieved without NIR irradiation. The development of AuNR-based NCs with multiple smart responsivenesses at tumors can provide a promising paradigm for solid tumor treatment via the cooperative effects of photothermal therapy and chemoembolization.


Assuntos
Neoplasias da Mama , Quitosana , Nanotubos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Ouro/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico
15.
Phytomedicine ; 123: 155249, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056144

RESUMO

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood. PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota. MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays. RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice. CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.


Assuntos
Dor Crônica , Prostatite , Humanos , Masculino , Camundongos , Animais , Prostatite/tratamento farmacológico , RNA Ribossômico 16S , Inflamação/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Dor Pélvica/metabolismo , Intestinos , Akkermansia , Xantofilas
16.
Bioresour Technol ; 393: 130155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38056681

RESUMO

Landfill leachate treatment is a major challenge in wastewater treatment. In this study, two sulfur-based autotrophic-heterotrophic denitrification biofilters (Ra biofilter with room-temperature molded filler and Rb biofilter with melt molded filler) were used to treat kitchen-landfill leachate at low temperatures. The effects of reflux ratio, concentrations of NaHCO3, and Na2S2O3 on the total nitrogen removal efficiency were analyzed, and based on response surface methodology, the optimum parameters were determined. After optimization, the total nitrogen removal efficiency for the Ra and Rb biofilters increased by 83% and 81%, respectively. Moreover, sulfur-based autotrophic denitrification accounted for more than 70% of the nitrogen removal in both biofilters. Based on high-throughput sequencing results, the functional bacteria exhibited high abundance in the Ra biofilter, indicating that the room-temperature molded filler favored the enrichment of functional bacteria. These findings were important for optimizing the operation of sulfur autotrophic-heterotrophic denitrification biofilters at low temperatures.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Desnitrificação , Temperatura , Anaerobiose , Reatores Biológicos/microbiologia , Processos Autotróficos , Enxofre , Nitrogênio , Nitratos
17.
Aging (Albany NY) ; 15(17): 8851-8872, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37683130

RESUMO

A-kinase anchoring protein 8L (AKAP8L) belong to the A-kinase anchoring protein (AKAP) family. Recent studies have proved that AKAP8L is associated with the progression of various tumors. To establish a more complete understanding of the significance of AKAP8L across various types of cancers, we conducted a detailed analysis of multiple histological datasets, including the level of gene expression in pancancer, biological function, molecular characteristics, as well as the diagnostic and prognostic value of AKAP8L in pancancer. Furthermore, we focused on renal clear cell carcinoma (KIRC), and of explored the correlation of AKAP8L with clinical characteristics, prognosis of distinct patient subsets, co-expression genes and differentially expressed genes (DEG). We also performed the immunohistochemical staining and semi-quantitative verification of the monoclonal antibody established by AKAP8L. Our findings indicate that AKAP8L expression varied significantly not only across most cancer types, but also across different cancer molecules and immune subtypes. In addition, the robust ability to accurately predict cancer and its strong correlation with the prognosis of cancer strongly suggest that AKAP8L may be a potential biomarker for cancer diagnosis and prognosis. Furthermore, the high expression levels of AKAP8L were related to the worse overall survival (OS), disease-specific survival (DSS) as well as progression-free interval (PFI) of KIRC with statistical significance, especially among distinct clinical subgroups of KIRC. To sum up, AKAP8L has the potential to serve as a critical molecular biomarker for the diagnosis and prognosis of pancancer, an independent prognostic risk factor of KIRC, and a novel molecular target for cancer therapies.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Proteínas de Ancoragem à Quinase A/genética , Anticorpos Monoclonais , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Prognóstico
18.
BMC Cancer ; 23(1): 837, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679715

RESUMO

BACKGROUND: RNASET2 has been identified as an oncogene with anti-angiogenic and immunomodulatory effects in a variety of cancers, but its function in clear cell renal cell carcinoma (ccRCC) is still not well understood. METHODS: The RNASET2 expression matrix was extracted from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and analyzed for diagnostic and prognostic value. RNASET2 mRNA expression was detected by quantitative polymerase chain reaction (qPCR) in ccRCC patients and renal cancer cell lines. Wound healing assay, transwell assay, western blotting, and tube formation assays were used to evaluate the function of RNASET2 in renal cancer in vitro. In addition, transcriptome sequencing was performed on knockdown RNASET2 kidney cancer cells to analyze their potential signaling pathways. Moreover, the immune microenvironment and mutational status were evaluated to predict the potential mechanisms of RNASET2 involvement in renal cancer progression. Sensitivity to common chemotherapeutic and targeted agents was assessed according to the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: RNASET2 expression was significantly upregulated in ccRCC tissues and renal cancer cell lines, predicting poor prognosis for patients. In vitro experiments showed that silencing RNASET2 inhibited the migration and pro-angiogenic ability of renal cancer cells. Transcriptome sequencing suggested its possible involvement in the remodeling of the immune microenvironment in renal cell carcinoma. Furthermore, bioinformatics analysis and immunohistochemical staining showed that RNASET2 was positively correlated with the infiltration abundance of regulatory T cells. Finally, we mapped the mutational landscape of RNASET2 in ccRCC and found its predictive value for drug sensitivity. CONCLUSIONS: Our results suggest that RNASET2 is a promising biomarker and therapeutic target in ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Biomarcadores , Neoplasias Renais/genética , Microambiente Tumoral , Ribonucleases , Proteínas Supressoras de Tumor
19.
Front Plant Sci ; 14: 1201553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528988

RESUMO

In woody plants, bark is an important protective tissue which can participate in photosynthesis, manage water loss, and transport assimilates. Studying the bark anatomical traits can provide insight into plant environmental adaptation strategies. However, a systematic understanding of the variability in bark anatomical traits and their drivers is lacking in woody plants. In this study, the bark anatomical traits of 23 Picea species were determined in a common garden experiment. We analyzed interspecific differences and interpreted the patterns in bark anatomical traits in relation to phylogenetic relationships and climatic factors of each species according to its global distribution. The results showed that there were interspecific differences in bark anatomical traits of Picea species. Phloem thickness was positively correlated with parenchyma cell size, possibly related to the roles of parenchyma cells in the radial transport of assimilates. Sieve cell size was negatively correlated with the radial diameter of resin ducts, and differences in sieve cells were possibly related to the formation and expansion of resin ducts. There were no significant phylogenetic signals for any bark anatomical trait, except the tangential diameter of resin ducts. Phloem thickness and parenchyma cell size were affected by temperature-related factors of their native range, while sieve cell size was influenced by precipitation-related factors. Bark anatomical traits were not significantly different under wet and dry climates. This study makes an important contribution to our understanding of variability in bark anatomical traits among Picea species and their ecological adaptations.

20.
J Endourol ; 37(9): 1028-1036, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37485569

RESUMO

Objective: To compare the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) vs laparoscopic partial nephrectomy (LPN) in the treatment of central renal angiomyolipomas (AMLs). Methods: We retrospectively analyzed the clinical data of 103 patients who were treated with either RAPN or LPN for central AMLs between January 2017 and June 2022. Propensity scores were matched according to sex, age, laterality, body mass index, symptoms, diameter of tumor, location of tumor distribution, R.E.N.A.L score, preoperative hemoglobin, preoperative serum creatinine, preoperative estimated glomerular filtration rate, chronic disease, previous abdominal surgery, preoperative selective arterial embolization, American Society of Anesthesiologists scale, and duration of follow-up, and after matching, perioperative and prognostic data of the two groups were compared. Results: A total of 57 patients underwent RAPN, and 46 patients underwent LPN. Before matching, there were more complex AMLs in the RAPN group, and R.E.N.A.L scores differed between the two groups (10 vs 9, p < 0.001). After matching, the median warm ischemic time in the RAPN group was significantly shorter than that in the LPN group (21.5 minutes vs 28 minutes, p = 0.034), as well as the median time of postoperative mobilization (1 day vs 2 days, p < 0.001). The other indicators were not significantly different between the groups. Conclusions: For central AMLs, both RAPN and LPN were safe and feasible surgical treatments, but RAPN might be associated with shorter warm ischemia time and earlier postoperative mobilization.


Assuntos
Angiomiolipoma , Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Angiomiolipoma/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Nefrectomia , Resultado do Tratamento
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