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As the Third Pole of the world, the Tibetan Plateau (TP) is sensitive to anthropogenic influences. Biomass combustion is one of the most important anthropogenic sources of mercury (Hg) emissions in the TP. However, due to the lack of knowledge about Hg emission characteristics and activity levels in the plateau, atmospheric Hg emissions from biomass combustion in the TP are under large uncertainties. Here, based on pilot-scale experiments, we found that particle-bound mercury (PBM; mean of 83.1-87.7 ng/m3) occupied 17.93-49.31% of the total emitted Hg and the PBM δ202Hg values (average -1.65 to -0.77) were significantly higher than those of the corresponding feeding biomass. The Δ200Hg values of total gaseous mercury and PBM were more negative (-0.08 to -0.05) than other anthropogenic emissions, providing unique isotopic fingerprints for this sector. Together with the investigated local activity levels, Hg emissions from biomass combustion reached 402 ± 74 kg/a, which were dozens of times higher than previous estimates. The emissions were characterized by conspicuous spatial heterogeneity, concentrated in the northern and central TP. Specialized Hg emissions and the Hg isotope fingerprint of local biomass combustion can aid in evaluating the influence of this sector on the fragile ecosystems of the TP.
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Mercúrio , Mercúrio/análise , Isótopos de Mercúrio/análise , Tibet , Ecossistema , Biomassa , Monitoramento AmbientalRESUMO
For revealing molecular markers related to the traits of multiple lumbar vertebrae in sheep, we analyze the relationship between NR6A1 gene polymorphism and lumbar vertebrae number traits in Xinjiang Kazakh sheep. Lumbar muscle tissues were collected from 6-lumbar spine (L6) Kazak sheep and 7-lumbar spine (L7) Kazak sheep and the intron-8 of NR6A1 gene was amplified by PCR. The SNP locus was detected by the PCR-SSCP method. One-Way ANOVA and an Independent Chi-square Test is adopted to analyze the genotype association with lumbar spine number variation. There were two SNP loci in the intron-8 of the NR6A1 gene: IVS8-188 and IVS8-281. One-Way ANOVA and Independent Chi-square Test indicated a significant association between IVS8-281 and lumbar spine number. The SNP locus of NR6A1 gene intron 8 (IVS8-281G > A) could play a certain role in the variation of lumbar spine number in Xinjiang Kazakh sheep and demonstrates potential to accelerate the sheep breeding of selection process.
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Vértebras Lombares , Polimorfismo Genético , Animais , Ovinos , Íntrons , Fenótipo , GenótipoRESUMO
BACKGROUND: This study incorporates fundamental research referring to considerable amounts of gene-sequencing data and bioinformatics tools to analyze the pathological mechanisms of diffuse large B-cell lymphoma (DLBCL). METHODS: A lncRNA-miRNA-mRNA ceRNA network of DLBCL was constructed through database analysis combining GTEx and TCGA. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. After LINC00963 or miR-320a overexpression in vitro, western blot was performed to assess the protein levels of UPR sensors (GRP78, p-IRE1, IRE1, active ATF6, ATF4 and XBP1), along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62). Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay. RESULTS: Following LINC00963 overexpression in vitro, SUDHL4 cell line showed a marked increase in the level of UPR-related GRP78, p-IRE1 and spliced XBP-1/XBP-1(s), apoptosis-related Bax and cleaved caspase 3, as well as autophagy-related Beclin1 and LC3II, whereas miR-320a mimic greatly diminished the effects of LINC00963 overexpression. Moreover, LINC00963 targeted miR-320a while miR-320a bound to the 3'UTR of XBP1. It was also found that LINC00963 overexpression resulted in significantly delayed tumor growth in a xenograft model of DLBCL. CONCLUSION: Mechanistically, LINC00963/miR-320a regulated XBP1-apoptosis pathway and autophagy, implying the therapeutic potential of this pathway for selective targeting. The data presented here illustrated the mechanism of LINC00963/miR-320a/XBP1 in DLBCL for the first time.
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BACKGROUND: Bovine viral diarrhea (BVD) which is caused by Bovine viral diarrhea virus (BVDV), is an acute, contagious disease. In spite of the use of vaccines and elimination projects, BVDV still causes severe economic losses to the cattle industry for the past few years. The current study presents a preliminary analysis of the pathogenic mechanisms from the perspective of protein expression levels in infected host cells at different points in time to elucidate the infection process associated with BVDV. METHODS: We used the isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with liquid chromatography-tandem mass spectrometric (LC-MS/MS) approach for a quantitative proteomics comparison of BVDV NADL-infected MDBK cells and non-infected cells. The functions of the proteins were deduced by functional annotation and their involvement in metabolic processes explored by KEGG pathway analysis to identify their interactions. RESULTS: There were 357 (47.6% downregulated, 52.4% upregulated infected vs. control), 101 (52.5% downregulated, 47.5% upregulated infected vs. control), and 66 (21.2% downregulated, 78.8% upregulated infected vs. control) proteins were differentially expressed (fold change > 1.5 or < 0.67) in the BVDV NADL-infected MDBK cells at 12, 24, and 48 h after infection. GO analysis showed that the differentially expressed proteins (DEPs) are mainly involved in metabolic processes, biological regulation and localization. KEGG enrichment analysis showed that some signaling pathways that involved in the regulation of BVDV NADL-infection and host resistance are significantly (P < 0.05) enriched at different stages of the BVDV NADL-infection, such as Endocytosis signaling pathway, FoxO signaling pathway, Homologous recombination signaling pathway and Lysosome pathway. CONCLUSIONS: These results revealed that the DEPs in BVDV NADL-infected MDBK cells have a wide range of regulatory effects; in addition, they provide a lot of resources for the study of host cell proteomics after BVDV infection.
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Doença das Mucosas por Vírus da Diarreia Viral Bovina , Vírus da Diarreia Viral Bovina , Proteoma , Animais , Bovinos , Linhagem Celular , Cromatografia Líquida , Diarreia , Proteômica , Espectrometria de Massas em TandemRESUMO
The 1.5 °C pathways initially promoted by the challenges presented by climate change could bring substantial air quality-related benefits. However, since there is a lack of comprehensive assessment on emissions of air pollutants, meteorology, air quality, and heatwave occurrences under different climate goals, how significant the clean air cobenefits compared with the direct climate-related impact is uncertain. In this study, we assess the cobenefits of 1.5 °C pathways for air quality in China by linking multiple shared socioeconomic pathways, ensembling simulations of regional climate-air quality dynamic downscaling and an air pollution and climate-related health assessment model, and compare different kinds of benefits: the health benefits from direct slowing climate (reduced heatwaves) versus the health cobenefits from air quality improvement (the improved air quality from reduced air pollutants versus meteorological changes). The benefit of reduced air pollution emissions associated with sustainable development under 1.5 °C pathways dominated the overall impact, which could avoid 1â¯589â¯000 PM2.5-related and 526â¯000 O3-related deaths in 2050. Correspondingly, the impact of changed meteorology on air quality would avoid additional 8000 PM2.5-related deaths in 2050 under 1.5 °C pathways yet would lead to 22â¯000 O3-related deaths. Also, the heatwave-related deaths could be avoided by 7000. The substantial anthropogenic emission reduction cobenefits of 1.5 °C pathways in improving air quality significantly exceed the direct climate (heatwave-related) benefits and completely offset the impact of meteorological changes' impact on air pollution under climate change.
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Coal preparation is effective in controlling primary mercury emissions in coal combustion systems; however, the combustion of coal preparation byproducts may cause secondary emissions. The inconsistent coal preparation statistics, unclear mercury distribution characteristics during coal preparation, and limited information regarding the byproduct utilization pathways lead to great uncertainty in the evaluation of the effect of coal preparation in China. This study elucidated the mercury distribution in coal preparation based on the activity levels of 2886 coal preparation plants, coal mercury content database, tested mercury distribution factors of typical plants, and then traced the mercury flows and emissions in the downstream sectors using a cross-industry mercury flow model. We found that coal preparation altered the mercury flows by reducing 68 tonnes of mercury to sectors such as coking and increasing the flows to byproduct utilization sectors. Combusting cleaned coal rather than raw coal reduced the mercury emissions by 47 tonnes; however, this was offset by secondary mercury emissions. Coal gangue spontaneous combustion and the cement kiln coprocessing process were dominant secondary emitters. Our results highlight the necessity of whole-process emission control of atmospheric mercury based on flow maps. Future comprehensive utilization of wastes in China should fully evaluate the potential secondary mercury emissions.
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Poluentes Atmosféricos , Mercúrio , Poluentes Atmosféricos/análise , China , Carvão Mineral/análise , Indústrias , Mercúrio/análise , Fenômenos Físicos , Centrais ElétricasRESUMO
The absorption of phospholipid may improve the fluidity of membrane and enzyme activities. Phospholipids also play a role in promoting Caveolae formation and membrane synthesis. Caveolin-1 has a significant effect on signaling pathways involved in regulating cell proliferation and stress responsiveness. Thus, we can speculate that Caveolin-1 could affect the sense of environmental stress. We use Chang liver cell line to investigate the ability of Caveolin-1 to modulate the cellular response to ethanol injury. Caveolin-1 downregulate cells (Cav-1(-/-)) were established by stable transfecting with psiRNA-CAV1 plasmids, which were more sensitive to toxic effects of ethanol than the untransfected parental cells (WT). Releasing of ALT and electric conductivity were changed significantly in Cav-1(-/-) cells compared with WT. Caveolin-1 gene silencing could obviously down-regulate the activities of protein kinase C-α (PKC-α) and phospho-p42/44 MAP kinase, indicating cell proliferation and self-repairing abilities were inhibited. However, the levels of Caveolin-1 and PKC-α were increased by phosphatidylcholine administration. The results indicated that the inhibition of lipid peroxidation by phosphatidylcholine could lead to the prevention of membrane disruption, which closely correlated with the level of Caveolin-1. Since the protective effects of phosphatidylcholine against ethanol-induced lipid peroxidation might be regulated by phospholipid-PKC-α signaling pathway, related with Caveolin-1, the potential effects of phosphatidylcholine on membranes need to be verified.
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Caveolina 1/metabolismo , Etanol/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fosfatidilcolinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Caveolina 1/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilcolinas/isolamento & purificação , Plasmalogênios/isolamento & purificação , Proteína Quinase C-alfa/metabolismo , SuínosRESUMO
BACKGROUND: The mineralocorticoid receptor plays an important pathophysiological role in cardiorenal diseases by causing inflammation and fibrosis. Mineralocorticoid receptor antagonists (MRAs) are well known in treating cardiovascular disease and diverse nephropathies. However, the first-generation MRA (spironolactone) and the second-generation MRA (eplerenone) remain underutilized because of the risk of inducing severe adverse events. As a selective nonsteroidal MRA, finerenone is safer and more effective and improves cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the effect of finerenone on cardiorenal outcomes in patients of different races and kidney function (estimated glomerular filtration rate) is unclear. SUMMARY: In this review, we summarized the impact of finerenone on patients with CKD and T2DM from randomized controlled trials. The synthesis of published data aims to address the questions pertaining to the cardiorenal benefits of finerenone among various racial groups and different levels of kidney function. KEY MESSAGE: Finerenone presents racial differences and effects associated with kidney function in CKD and T2DM patients. Due to the limited data for subgroups, it is prudent to approach the conclusion with caution.
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Taxa de Filtração Glomerular , Antagonistas de Receptores de Mineralocorticoides , Naftiridinas , Insuficiência Renal Crônica , Humanos , Naftiridinas/uso terapêutico , Naftiridinas/farmacologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Rim/fisiopatologia , Rim/efeitos dos fármacos , Grupos RaciaisRESUMO
Pancreatic cancer (PC) is characterized by its notably poor prognosis and high mortality rate, underscoring the critical need for advancements in its diagnosis and therapy. Gold nanoparticles (AuNPs), with their distinctive physicochemical characteristics, demonstrate significant application potential in cancer therapy. For example, upon exposure to lasers of certain wavelengths, they facilitate localized heating, rendering them extremely effective in photothermal therapy. Additionally, their extensive surface area enables the conjugation of therapeutic agents or targeting molecules, increasing the accuracy of drug delivery systems. Moreover, AuNPs can serve as radiosensitizers, enhancing the efficacy of radiotherapy by boosting the radiation absorption in tumor cells. Here, we systematically reviewed the application and future directions of AuNPs in the diagnosis and treatment of PC. Although AuNPs have advantages in improving diagnostic and therapeutic efficacy, as well as minimizing damage to normal tissues, concerns about their potential toxicity and safety need to be comprehensively evaluated.
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BACKGROUND: Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes. RESULTS: Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], -0.59, 95% CI, -0.73 to -0.45, p < .01) vs (WMD, -0.29, 95% CI, -0.32 to -0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, -5.12, 95% CI, -5.84 to -4.41, p < .01) compared to non-Asians (WMD, -3.64, 95% CI, -4.38 to -2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (p < .01). CONCLUSIONS: Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%.
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Povo Asiático , Diabetes Mellitus Tipo 2 , Antagonistas de Receptores de Mineralocorticoides , Insuficiência Renal Crônica , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etnologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etnologia , Povo Asiático/estatística & dados numéricos , Taxa de Filtração Glomerular , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etnologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rim/efeitos dos fármacos , Rim/fisiopatologia , Rim/patologia , Naftiridinas , Pirróis , SulfonasRESUMO
Macrophages, as the largest immune cell group in tumour tissues, play a crucial role in influencing various malignant behaviours of tumour cells and tumour immune evasion. As the research on macrophages and cancer immunotherapy develops, the importance of appropriate research models becomes increasingly evident. The development of organoids has bridged the gap between traditional two-dimensional (2D) cultures and animal experiments. Recent studies have demonstrated that organoids exhibit similar physiological characteristics to the source tissue and closely resemble the in vivo genome and molecular markers of the source tissue or organ. However, organoids still lack an immune component. Developing a co-culture model of organoids and macrophages is crucial for studying the interaction and mechanisms between tumour cells and macrophages. This paper presents an overview of the establishment of co-culture models, the current research status of organoid macrophage interactions, and the current status of immunotherapy. In addition, the application prospects and shortcomings of the model are explained. Ultimately, it is hoped that the co-culture model will offer a preclinical testing platform for maximising a precise cancer immunotherapy strategy.
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Vanin1 (VNN1) is an exogenous enzyme with pantetheinase activity that mainly exerts physiological functions through enzyme catalysis products, including pantothenic acid and cysteamine. In recent years, the crosstalk between VNN1 and metabolism and oxidative stress has attracted much attention. As a result of the ability of VNN1 to affect multiple metabolic pathways and oxidative stress to exacerbate or alleviate pathological processes, it has become a key component of disease progression. This review discusses the functions of VNN1 in glucolipid metabolism, cysteamine metabolism, and glutathione metabolism to provide perspectives on VNN1-targeted therapy for chronic diseases.
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Cisteamina , Estresse Oxidativo , Humanos , Cisteamina/metabolismo , Ácido Pantotênico/metabolismo , Doença Crônica , Progressão da Doença , Amidoidrolases/metabolismo , Proteínas Ligadas por GPI/metabolismoRESUMO
Purpose: Proximal tubular epithelial cell (PTEC) is vulnerable to injury in diabetic kidney disease (DKD) due to high energy expenditure. The injured PTECs-derived profibrotic factors are thought to be driving forces in tubulointerstitial fibrosis (TIF) as they activate surrounding fibroblasts. However, the mechanisms remain unclear. Methods: The diabetes with uninephrectomy (DKD) rats were used to evaluated renal histological changes and the expression of Claudin-2 by immunofluorescence staining. Then, Claudin-2 expression in PTECs were modulated and subsequently determined the proliferation and activation of fibroblasts by building a transwell co-culture system in normal glucose (NG)or high glucose (HG) condition. Results: Decreased expression of Claudin-2 in PTECs accompanied by tight junction disruption and increased interstitial fibrosis, were detected in DKD rats. In vitro, downregulated Claudin-2 in PTECs promoted proliferation and activation of fibroblasts, which coincided with elevated expression of profibrotic connective tissue growth factor (CTGF) in PTECs. Silenced CTGF inhibited the profibrotic of PTECs via Claudin-2 inhibition. Fibroblasts co-cultured with PTECs transitioned more to myofibroblasts and generated extracellular matrix (ECM) significantly in response to high glucose (HG) stimulation whereas overexpression of Claudin-2 in PTECs reversed the above results. Upregulating CTGF disrupted the beneficial anti-fibrosis effects obtained by overexpression of Claudin-2 in HG condition. Conclusion: Our study suggested that Claudin-2 in PTECs, a key mediator of paracellular cation and water transport, promotes the activation and proliferation of surrounding fibroblasts significantly via CTGF in a paracrine manner.
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INTRODUCTION: Tirzepatide is a novel hypoglycemic agent for type 2 diabetes mellitus (T2DM). However, the pathophysiology of T2DM in Asians is different from that in non-Asians, and there is no evidence to explain the differences in the efficacy and safety of tirzepatide between different races. METHODS: A literature search was conducted in China National Knowledge Infrastructure (CNKI), PubMed, Cochrane Library, Clinical Trials.gov, and Embase databases for clinical studies of tirzepatide for T2DM. The data extraction process was done independently by two authors. All analyses were performed using STATA 14.0 software and Review Manager 5.3 software. RESULTS: A total of 2118 patients with T2DM from 6 studies were involved, with doses of tirzepatide ranging from 5 to 15 mg administered subcutaneously once weekly. The results showed that compared with control/placebo, tirzepatide was more effective in decreasing fasting blood glucose (FBG) in non-Asians than in Asians, and 10 mg rather than 15 mg was the optimal dose to decrease FBG. Similarly, non-Asians were more effective than Asians in improving glycated hemoglobin (HbA1c). Asians were significantly more effective than non-Asians in reducing body weight and ≥ 5% weight loss. In terms of adverse events, the incidence of gastrointestinal adverse events was higher in Asians than in non-Asians at the same dose, while the incidence of metabolic and nutrition disorders was higher in non-Asians than in Asians. CONCLUSION: Tirzepatide is a novel agent for the treatment of diabetes and has different efficacy in Asians and non-Asians. Asians were more likely to experience weight loss and gastrointestinal adverse events, whereas non-Asians were more likely to have better glycemic control and more metabolic and nutritional disorders. TRIAL REGISTRATION: PROSPERO registration no. CRD42023489588.
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Background: Colorectal cancer is influenced by several factors such as unhealthy habits and genetic factors. C1QB has been linked to a number of malignancies. However, uncertainty surrounds the connection between C1QB and CRC. Therefore, this study aimed to explore a bidirectional causal relationship of C1QB as a drug target in CRC through Mendelian randomization (MR) analysis. Methods: The GWASs for C1QB and CRC were obtained from the Integrative Epidemiology Unit Open GWAS database. There were five strategies to investigate MR. Sensitivity analysis was carried out via tests for heterogeneity, horizontal pleiotropy and leave-one-out effects to evaluate the dependability of the MR analysis results. Furthermore, colocalization analysis of C1QB and CRC, protein-protein interaction network and drug prediction according to exposure factors as well as phenotype scanning were performed. Results: The results of forward MR analysis demonstrated that C1QB was a risk factor for CRC (OR = 1.104, p = 0.033). However, we did not find a causal relationship between CRC and C1QB (reverse MR). Rs294180 and rs291985 corresponded to the same linkage interval and had the potential to influence C1QB and CRC, respectively. The PPI results demonstrated that C1QB interacted with 10 genes (C1QA, C1QC, C1R, C1S, C2, C4A, C4B, CALR, SERPING1, and VSIG4). Additionally, 21 medications were predicted to match C1QB. Molecular docking data, including for benzo(a)pyrene, 1-naphthylisothiocyanate, calcitriol and medroxyprogesterone acetate, revealed excellent binding for drugs and proteins. Moreover, we identified 29 diseases that were associated with C1QB and related medicines via disease prediction and intersection methods. As a therapeutic target for CRC, phenotypic scanning revealed that C1QB does not significantly affect weight loss, liver cirrhosis, or nonalcoholic fatty liver disease, but might have protective impacts on ovarian cancer and melanoma. Conclusion: The results highlight a causal relationship between C1QB and CRC and imply an oncogenic role for C1QB in CRC, as potential drug targets. Drugs designed to target C1QB have a greater chance of success in clinical trials and are expected to help prioritize CRC drug development and reduce drug development costs. That provided a theoretical foundation and reference for research on CRC and C1QB in MR.
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BACKGROUND: Emodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application. PURPOSE: We aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored. METHODS: M-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells. RESULTS: The levels of inflammatory mediators in macrophages were markedly decreased after treatment with M-CS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-α and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages. CONCLUSION: M-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment.
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Emodina , Metabolismo dos Lipídeos , Macrófagos , Nanocápsulas , Pancreatite , Animais , Emodina/farmacologia , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pancreatite/tratamento farmacológico , Células RAW 264.7 , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Anti-Inflamatórios/farmacologia , Quitosana/farmacologia , Quitosana/química , Camundongos Endogâmicos C57BL , Lipopolissacarídeos , Reprogramação MetabólicaRESUMO
PURPOSE: The current guidelines state that the functional imaging choice in the evaluation of metastatic pheochromocytoma and paraganglioma (PPGL) is 68 Ga-DOTATATE PET/CT. 18 F-meta-fluorobenzylguanidine ( 18 F-MFBG) is a new PET tracer and an analog of meta-iodobenzylguanidine (MIBG). This study aimed to compare 18 F-MFBG and 68 Ga-DOTATATE PET/CT in patients with metastatic PPGL. PATIENTS AND METHODS: Twenty-eight patients with known metastatic PPGL were prospectively recruited for this study. All patients underwent both 18 F-MFBG and 68 Ga-DOTATATE PET/CT studies within 1 week. Lesion numbers detected were compared between these 2 studies. RESULTS: 18 F-MFBG PET/CT was positive for detecting metastases in all patients, whereas positive results of 68 Ga-DOTATATE PET/CT were in 27 (96.4%) patients. A total of 686 foci of metastatic lesions were detected by both 18 F-MFBG and 68 Ga-DOTATATE imaging. In addition, 33 foci of abnormal activity were only detected by 18 F-MFBG, whereas 16 foci were only shown on 68 Ga-DOTATATE PET/CT. CONCLUSIONS: Our data suggest that 18 F-MFBG PET/CT is an effective imaging method in the evaluation of metastatic PPGL and could be alternative of 68 Ga-DOTATATE PET/CT in this clinical setting.
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Neoplasias das Glândulas Suprarrenais , Segunda Neoplasia Primária , Compostos Organometálicos , Paraganglioma , Neoplasias do Sistema Nervoso Periférico , Feocromocitoma , Humanos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Paraganglioma/diagnóstico por imagem , Feocromocitoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos RadiofarmacêuticosRESUMO
Subsequently to the publication of this paper, the authors have realized that they included the incorrect data in Fig. 5 for the p21 blots on p. 8. The corrected version of Fig. 5, featuring the data that were intended to have been included in this figure for the p21 blots, is shown on the next page. Furthermore, the authors wish to make the following changes to the text in the paper (changes are highlighted in bold): i) on p. 2, lefthand column, line 16, the final sentence in the penultimate paragraph of the Introduction should have read as: "However, the functions of RNAbinding protein (RBP) IGF2BP2, and the interactions between IGF2BP2 and NT5DC2 in DLBCL remain to be explored."; ii) In the Materials and methods section, subsection "RNA pulldown assay", the first sentence should be revised to: "An RNA pull down kit (cat. no. P0202: Geneseed) was used to perform RNA pull down assay according to the manufacturer's instructions."; iii) In the Results section on p. 3, the subsection "NT5DC2 is upregulated in DLBC cells and knockdown of NT5DC2 inhibits proliferation of DLBC cells.", the second sentence should be revised as follows: "mRNA and protein expression of NT5DC2 was highest in OCILy7 cells compared with that in the other DLBC cell lines (Fig. 1A)."; iv) The first two sentences in the following paragraph should have read as follows: "mRNA and protein expression levels of NT5DC2 were decreased in DLBC cells transfected with shRNANT5DC2#1/2 compared with the untransfected group, and were lower in the shRNANT5DC2#2 group compared with the shRNANT5DC2#1 group (Fig. 1B)."; and v) On p. 7, lefthand column, the sentence commencing on line 59 should have read as: "The present results indicated that NT5DC2 was increased in DLBCL cells...". Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree with the publication of this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 26: 286, 2022; DOI: 10.3892/mmr.2022.12802].
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The energy needs of tubular epithelial components, especially proximal tubular epithelial cells (PTECs), are high and they heavily depend on aerobic metabolism. As a result, they are particularly vulnerable to various injuries caused by factors such as ischemia, proteinuria, toxins, and elevated glucose levels. Initial metabolic and phenotypic changes in PTECs after injury are likely an attempt at survival and repair. Nevertheless, in cases of recurrent or prolonged injury, PTECs have the potential to undergo a transition to a secretory state, leading to the generation and discharge of diverse bioactive substances, including transforming growth factor-ß, Wnt ligands, hepatocyte growth factor, interleukin (IL)-1ß, lactic acid, exosomes, and extracellular vesicles. By promoting fibroblast activation, macrophage recruitment, and endothelial cell loss, these bioactive compounds stimulate communication between epithelial cells and other interstitial cells, ultimately worsening renal damage. This review provides a summary of the latest findings on bioactive compounds that facilitate the communication between these cellular categories, ultimately leading to the advancement of tubulointerstitial fibrosis (TIF).
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Nefropatias , Rim , Humanos , Células Epiteliais , Células Endoteliais , Interleucina-1beta , FibroseRESUMO
Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, accounting for the second most common cause of gastrointestinal tumors. As one of the intestinal barriers, gut bacteria form biofilm, participate in intestinal work, and form the living environment of intestinal cells. Metagenomic next-generation sequencing (mNGS) of the gut bacteria in a large number of CRC patients has been established, enabling specific microbial signatures to be associated with colorectal adenomato-carcinoma. Gut bacteria are involved in both benign precursor lesions (polyps), in situ growth and metastasis of CRC. Therefore, the term tumorigenic bacteria was proposed in 2018, such as Escherichia coli, Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, etc. Meanwhile, bacteria toxins (such as cytolethal distending toxin (CDT), Colibactin (Clb), B. fragilis toxin) affect the tumor microenvironment and promote cancer occurrence and tumor immune escape. It is important to note that there are differences in the bacteria of different types of CRC. In this paper, the role of tumorigenic bacteria in the polyp-cancer transformation and the effects of their secreted toxins on the tumor microenvironment will be discussed, thereby further exploring new ideas for the prevention and treatment of CRC.