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1.
Clin Exp Immunol ; 2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-36966354

RESUMO

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

2.
Thromb Res ; 225: 39-46, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36948020

RESUMO

The significance of rare germline mutations in transplant-associated thrombotic microangiopathy (TA-TMA) is not well studied. We performed a genetic association study in 100 adult TA-TMA patients vs. 98 post-transplant controls after matching by race, sex, and year. We focused on 5 pathways in complement, von Willebrand factor (VWF) function and related proteins, VWF clearance, ADAMTS13 function and related proteins, and endothelial activation (3641variants in 52 genes). In the primary analysis focused on 189 functional rare variants, no differential variant enrichment was observed in any of the pathways; specifically, 29 % TA-TMA and 33 % controls had at least 1 rare complement mutation. In the secondary analysis focused on 37 rare variants predicted to be pathogenic or likely pathogenic by ClinVar, Complement Database, or REVEL in-silico prediction tool, rare variants in the VWF clearance pathway were found to be significantly associated with TA-TMA (p = 0.008). On the gene level, LRP1 was the only one with significantly increased variants in TA-TMA in both analyses (p = 0.025 and 0.015). In conclusion, we did not find a significant association between rare variants in the complement pathway and TA-TMA; however, we discovered a new signal in the VWF clearance pathway driven by the gene LRP1 among likely pathogenic variants.

3.
Food Chem ; 417: 135903, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36924724

RESUMO

A film simultaneously with colorimetric, fluorescent and active functions was engineered using chitosan (CS) and polyvinyl alcohol (PVA) as the film matrix and curcumin-ß-cyclodextrin complex (Cur-ß-CD) as the indicator for freshness monitoring and maintaining of pork and shrimp. In addition to the efficacy of prolonging shelf life, the film's color could change from yellow to orange with ΔE > 5 and its fluorescence intensity could decrease during storage. The incorporation of PVA significantly enhanced the mechanical properties of CS film with tensile strength of 31.80 MPa and elongation at break of 127.22 %. The Cur-ß-CD improved the antioxidant and antibacterial properties, water contact angle (from 86.3° to 111.2°), water vapor permeability (from 3.28 × 10-10 g (m s Pa)-1 to 0.42 × 10-10 g (m s Pa)-1) and mechanical properties of CS/PVA film. These results show the potential of the film as promising alternatives for intelligent and active food packaging.

4.
Front Oncol ; 13: 1099624, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937390

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer kind. According to recent research, a fatty liver increases the risk of hepatocellular cancer. Nevertheless, the AMPK signaling pathway is crucial. In addition, 5'-AMP-activated protein kinase (AMPK) is strongly linked to alterations in the tumor microenvironment, such as inflammation, hypoxia, and aging. The objective of this study is to evaluate the impact of the AMPK signaling pathway on the progression of fatty liver to HCC. Methods: In this study, we established a mouse liver cancer model using high-fat diets and nano-nitrosamines (nano-DEN). In addition, we employed a transcriptomic technique to identify all mRNAs detected in liver samples at the 25th weekexpression of proteins linked with the LKB1-AMPK-mTOR signaling pathway, inflammation, aging, and hypoxia was studied in microarrays of liver cancer tissues from mice and humans. These proteins included p-AMPK, LKB1, mTOR, COX-2, ß-catenin, HMGB1, p16, and HIF-1α. Results: Data were collected at different times in the liver as well as in cancerous and paracancerous regions and analyzed by a multispectral imaging system. The results showed that most of the genes in the AMPK signaling pathway were downregulated. Prakk1 expression was upregulated compared to control group but downregulated in the cancerous regions compared to the paracancerous regions. Stk11 expression was downregulated in the cancerous regions. Mtor expression was upregulated in the cancerous regions. During liver cancer formation, deletion of LKB1 in the LKB1-AMPK-mTOR signaling pathway reduces phosphorylation of AMPK. It contributed to the upregulation of mTOR, which further led to the upregulation of HIF1α. In addition, the expression of ß-catenin, COX-2, and HMGB1 were upregulated, as well as the expression of p16 was downregulated. Discussion: These findings suggest that changes in the AMPK signaling pathway exacerbate the deterioration of disrupted energy metabolism, chronic inflammation, hypoxia, and cellular aging in the tumor microenvironment, promoting the development of fatty liver into liver cancer.

5.
Ann Hematol ; 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36943465

RESUMO

Acute myeloid leukemia (AML) is the most common hematopoietic malignancy with abnormal lipid metabolism. However, currently available information on the involvement of the alterations in lipid metabolism in AML development is limited. In this study, we demonstrate that FABP5 expression facilitates AML cell viability, protects AML cells from apoptosis, and maintains triglyceride production. Our bioinformatics analysis revealed that FABP5 expression was upregulated and correlated with unfavorable overall survival of AML patients. FABP5 expression may be used to distinguish normal and AML with high accuracy. FABP5-based risk score was an independent risk factor for AML patients. AML patients with highly expressed FABP5 predicted resistance to drugs. In vitro study showed that FABP5 expression was remarkably elevated in primary AML blasts and an AML cell line. Silencing FABP5 expression attenuated AML cell viability, reduced triglyceride production and lipid droplet accumulation, and induced apoptosis. We utilized AutoDock online tool to identify lycorine as an FABP5 inhibitor by binding FABP5 at amino acid residues Ile54, Thr56, Thr63, and Arg109. Lycorine treatment downregulated the expression levels of FABP5 and its target PPARγ, impaired AML cell viability, triggered apoptosis, and reduced triglyceride production in AML cells. These results demonstrate that FABP5 is critical for AML cell survival and highlight a novel metabolic vulnerability for AML.

6.
Int J Infect Dis ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36967037

RESUMO

OBJECTIVES: From March to June in 2021, the reported number of clinically diagnosed endemic typhus in Anhui and Hubei provinces of China nearly fourfold increased as compared with the monthly average number in last five years. The etiological and epidemiological investigation was initiated. METHODS: The clinical specimens from the reported patients and the potential vector ticks were collected for molecular and serological detection as well as cell culturing assay to identify the potential pathogen. RESULTS: PCR and sequence analysis of rrs and groEL showed that the pathogen from these patients was Ehrlichia sp. isolated from Haemaphysalis longicornis attached to these patients. Phylogenetic analysis based on 39 Ehrlichia genomes suggested that it should be taxonomically classified as a novel species, tentatively named "Candidatus Ehrlichia erythraense". Nineteen of 106 cases were confirmed as Candidatus Ehrlichia erythraense infections by PCR, sequencing, and/or serological tests. The most frequent symptoms for them were fever (100%), rash (100%), asthenia (100%), anorexia (100%), and myalgia (79%). CONCLUSIONS: The occurrence of the disease presenting with fever and rash in Anhui and Hubei provinces was caused by a novel species of genus Ehrlichia, physicians need to beware of this newly-discovered pathogen to ensure appropriate testing, treatment, and regional surveillance.

7.
Heliyon ; 9(3): e14232, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36967935

RESUMO

We used ancient DNA (aDNA) extraction methods to sequence museum voucher samples of Oligobrachia webbi, a frenulate siboglinid polychaete described from a northern Norwegian fjord over fifty years ago. Our sequencing results indicate a genetic match with the cryptic seep species, Oligobrachia haakonmosbiensis (99% pairwise identity for 574 bp mtCOI fragments). Due to its similarity with O. webbi, the identity of O. haakonmosbiensis has been a matter of debate since its description, which we have now resolved. Furthermore, our results demonstrate that chemosynthesis-based siboglinids, that constitute the bulk of the biomass at Arctic seeps are not seep specialists. Our data on sediment geochemistry and carbon and nitrogen content reveal reduced conditions in fjords/sounds, similar to those at seep systems. Accumulation and decomposition of both terrestrial and marine organic matter results in the buildup of methane and sulfide that apparently can sustain chemosymbiotic fauna. The occurrence of fjords and by extension, highly reducing habitats, could have led to Arctic chemosymbiotic species being relatively generalist with their habitat, as opposed to being seep or vent specialists. Our stable isotope analyses indicate the incorporation of photosynthetically derived carbon in some individuals, which aligns with experiments conducted on frenulates before the discovery of chemosynthesis that demonstrated their ability to take up organic molecules from the surrounding sediment. Since reduced gases in non-seep environments are ultimately sourced from photosynthetic processes, we suggest that the extreme seasonality of the Arctic has resulted in Arctic chemosymbiotic animals seasonally changing their degree of reliance on chemosynthetic partners. Overall, the role of chemosynthesis in Arctic benthos and marine ecosystems and links to photosynthesis may be complex, and more extensive than currently known.

8.
World J Clin Cases ; 11(8): 1712-1718, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36969995

RESUMO

Postoperative complications of phacoemulsification, such as corneal edema caused by human corneal endothelial cell (CEC) injury, are still a matter of concern. Although several factors are known to cause CEC damage, the influence of ultrasound on the formation of free radicals during surgery should be considered. Ultrasound in aqueous humor induces cavitation and promotes the formation of hydroxyl radicals or reactive oxygen species (ROS). ROS-induced apoptosis and autophagy in phacoemulsification have been suggested to significantly promote CEC injury. CEC cannot regenerate after injury, and measures must be taken to prevent the loss of CEC after phacoemulsification or other CEC injuries. Antioxidants can reduce the oxidative stress injury of CEC during phacoemulsification. Evidence from rabbit eye studies shows that ascorbic acid infusion during operation or local application of ascorbic acid during phacoemulsification has a protective effect by scavenging free radicals or reducing oxidative stress. Both in experiments and clinical practice, hydrogen dissolved in the irrigating solution can also prevent CEC damage during phacoemulsification surgery. Astaxanthin (AST) can inhibit oxidative damage, thereby protecting different cells from most pathological conditions, such as myocardial cells, luteinized granulosa cells of the ovary, umbilical vascular endothelial cells, and human retina pigment epithelium cell line (ARPE-19). However, existing research has not focused on the application of AST to prevent oxidative stress during phacoemulsification, and the related mechanisms need to be studied. The Rho related helical coil kinase inhibitor Y-27632 can inhibit CEC apoptosis after phacoemulsification. Rigorous experiments are required to confirm whether its effect is realized through improving the ROS clearance ability of CEC.

9.
Adv Mater ; : e2211332, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36971342

RESUMO

The tumor-associated macrophages (TAMs) in intratumoral hypoxic regions are key drivers of immune escape. Reprogramming the hypoxic TAMs to antitumor phenotype holds great therapeutic benefits but remains challenging for current drugs. Here, we report an in situ activated nanoglycocluster to realize effective tumor penetration and potent repolarization of hypoxic TAMs. Triggered by the hypoxia-upregulated matrix metalloproteinase-2 (MMP-2), the nanoglycocluster is self-assembled from the administered mannose-containing precursor glycopeptides, and presents densely-arrayed mannoses to multivalently engage with mannose receptors on M2-like TAMs for efficient phenotype switch. By virtue of the high diffusivity of precursor glycopeptides due to their low molecular mass and weak affinity with TAMs in perivascular regions, the nanoglycoclusters are capable of substantially accumulating in hypoxic areas to strongly interact with local TAMs. This enables the efficient repolarization of overall TAMs with a higher rate than the small-molecule drug R848 and CD40 antibody, and beneficial therapeutic effects in mouse tumor models especially when combined with PD-1 antibody. This on-demand activated immunoagent is endowed with tumor-penetrating property and inspires the design of diverse intelligent nanomedicines for hypoxia-related cancer immunotherapy. This article is protected by copyright. All rights reserved.

10.
Aging (Albany NY) ; 15(5): 1371-1393, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36863715

RESUMO

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/genética , Metilação , RNA , Redes Reguladoras de Genes , Voluntários Saudáveis
11.
Aging (Albany NY) ; 15(5): 1475-1495, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36863704

RESUMO

The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the "CIBERSORT" software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including MNS1, FRZB, OGN, and LUM, and four downregulated DEGs, SERP1NA3, RNASE2, FCN3 and SLCO4A1, were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.


Assuntos
Cardiomiopatias , Isquemia Miocárdica , Humanos , Nomogramas , Algoritmo Florestas Aleatórias , Isquemia Miocárdica/genética , Biologia Computacional , Lectinas , Peptídeos e Proteínas de Sinalização Intercelular
12.
Aging (Albany NY) ; 15(5): 1394-1411, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36863716

RESUMO

Lipid metabolism plays an essential role in the genesis and progress of acute myocardial infarction (AMI). Herein, we identified and verified latent lipid-related genes involved in AMI by bioinformatic analysis. Lipid-related differentially expressed genes (DEGs) involved in AMI were identified using the GSE66360 dataset from the Gene Expression Omnibus (GEO) database and R software packages. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to analyze lipid-related DEGs. Lipid-related genes were identified by two machine learning techniques: least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE). The receiver operating characteristic (ROC) curves were used to descript diagnostic accuracy. Furthermore, blood samples were collected from AMI patients and healthy individuals, and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the RNA levels of four lipid-related DEGs. Fifty lipid-related DEGs were identified, 28 upregulated and 22 downregulated. Several enrichment terms related to lipid metabolism were found by GO and KEGG enrichment analyses. After LASSO and SVM-RFE screening, four genes (ACSL1, CH25H, GPCPD1, and PLA2G12A) were identified as potential diagnostic biomarkers for AMI. Moreover, the RT-qPCR analysis indicated that the expression levels of four DEGs in AMI patients and healthy individuals were consistent with bioinformatics analysis results. The validation of clinical samples suggested that 4 lipid-related DEGs are expected to be diagnostic markers for AMI and provide new targets for lipid therapy of AMI.


Assuntos
Biologia Computacional , Infarto do Miocárdio , Humanos , Biomarcadores , Coenzima A Ligases/genética , Bases de Dados Factuais , Lipídeos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Fosfolipases , Fosfolipases A2 do Grupo I/metabolismo
13.
ACS Synth Biol ; 12(3): 639-656, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36867718

RESUMO

Terpenoids are a diverse group of compounds with isoprene units as basic building blocks. They are widely used in the food, feed, pharmaceutical, and cosmetic industries due to their diverse biological functions such as antioxidant, anticancer, and immune enhancement. With an increase in understanding the biosynthetic pathways of terpenoids and advances in synthetic biology techniques, microbial cell factories have been built for the heterologous production of terpenoids, with the oleaginous yeast Yarrowia lipolytica emerging as an outstanding chassis. In this paper, recent progress in the development of Y. lipolytica cell factories for terpenoid production with a focus on the advances in novel synbio tools and metabolic engineering strategies toward enhanced terpenoid biosynthesis is reviewed.


Assuntos
Engenharia Metabólica , Yarrowia , Engenharia Metabólica/métodos , Yarrowia/genética , Yarrowia/metabolismo , Terpenos/metabolismo , Vias Biossintéticas/genética , Biologia Sintética
14.
World J Clin Cases ; 11(7): 1656-1665, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36926395

RESUMO

BACKGROUND: IgG4-related disease (IgG4-RD) is a chronic fibrotic disease mediated by immunity recognized by clinicians in recent years. When the kidney is involved, it is called IgG4-related kidney disease (IgG4-RKD). IgG4-related tubulointerstitial nephritis (IgG4-TIN) is a representative manifestation of IgG4-RKD. IgG4-TIN can cause obstructive nephropathy complicated by retroperitoneal fibrosis (RPF). Cases of IgG4-TIN complicated with RPF are rare. Glucocorticoids are the first-line therapeutic medication for IgG4-RD and can significantly improve renal function. CASE SUMMARY: Herein, we report the case of a 56-year-old man with IgG4-RKD complicated with RPF. The patient presented to the hospital with complaints of elevated serum creatinine (Cr), nausea, and vomiting. During hospitalization, Cr was 1448.6 µmol/L, and serum IgG4 was increased. A total abdominal computed tomography (CT) scan and enhanced CT scan obviously indicated RPF. Although this patient had a long course and renal insufficiency, we performed a kidney biopsy. Renal biopsy showed that the renal tubulointerstitium had focal plasma cell infiltration and increased lymphocyte infiltration accompanied by fibrosis. After combining the biopsy results with immunohistochemistry, it was found that the absolute number of positive IgG4+ cells per high power field exceeded 10, and the ratio of IgG4/IgG was over 40%. Finally, the patient was diagnosed with IgG4-TIN complicated with RPF and given glucocorticoids as long-term maintenance therapy, helping him keep out of dialysis. After a follow-up of 19 mo, the patient had recovered well. Previous literature on IgG4-RKD and RPF was retrieved from PubMed to characterize the clinical and pathological features and to identify the diagnosis and treatment of IgG4-RKD. CONCLUSION: Our case report demonstrates the clinical characteristics of IgG4-RKD complicated with RPF. Serum IgG4 is a favorable indicator for screening. Performing renal biopsy actively plays a vital role in diagnosis and treatment, even if the patient has a long course and manifests with renal insufficiency. It is remarkable to treat IgG4-RKD with glucocorticoids. Hence, early diagnosis and targeted therapy are essential for reversing renal function and improving extrarenal manifestations in patients with IgG4-RKD.

15.
Int J Mol Sci ; 24(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36901724

RESUMO

The use of electronic nicotine dispensing systems (ENDS), also known as electronic cigarettes (ECs), is common among adolescents and young adults with limited knowledge about the detrimental effects on lung health such as respiratory viral infections and underlying mechanisms. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a protein of the TNF family involved in cell apoptosis, is upregulated in COPD patients and during influenza A virus (IAV) infections, but its role in viral infection during EC exposures remains unclear. This study was aimed to investigate the effect of ECs on viral infection and TRAIL release in a human lung precision-cut lung slices (PCLS) model, and the role of TRAIL in regulating IAV infection. PCLS prepared from lungs of nonsmoker healthy human donors were exposed to EC juice (E-juice) and IAV for up to 3 days during which viral load, TRAIL, lactate dehydrogenase (LDH), and TNF-α in the tissue and supernatants were determined. TRAIL neutralizing antibody and recombinant TRAIL were utilized to determine the contribution of TRAIL to viral infection during EC exposures. E-juice increased viral load, TRAIL, TNF-α release and cytotoxicity in IAV-infected PCLS. TRAIL neutralizing antibody increased tissue viral load but reduced viral release into supernatants. Conversely, recombinant TRAIL decreased tissue viral load but increased viral release into supernatants. Further, recombinant TRAIL enhanced the expression of interferon-ß and interferon-λ induced by E-juice exposure in IAV-infected PCLS. Our results suggest that EC exposure in human distal lungs amplifies viral infection and TRAIL release, and that TRAIL may serve as a mechanism to regulate viral infection. Appropriate levels of TRAIL may be important to control IAV infection in EC users.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vírus da Influenza A , Influenza Humana , Adolescente , Humanos , Adulto Jovem , Anticorpos Neutralizantes/metabolismo , Vírus da Influenza A/fisiologia , Pulmão/patologia , Fator de Necrose Tumoral alfa/metabolismo
16.
Bioresour Technol ; 376: 128858, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36907225

RESUMO

A sequential anaerobic digestion and phycoremediation process was employed to recover nutrients and remove pollutants from dairy wastewater (DW), while simultaneously producing biomethane and biochemicals. Anaerobic digestion of 100% DW achieved a methane content and production rate of 53.7% and 0.17 L/L/d, respectively. This was accompanied by the removal of 65.5% chemical oxygen demand (COD), 86% total solid (TS), and 92.8% volatile fatty acids (VFAs). The anaerobic digestate was then used to grow Chlorella sorokiniana SU-1. Using 25% diluted digestate as the medium, SU-1 could reach 4.64 g/L biomass concentration, with total nitrogen (TN), total phosphorus (TP) and COD removal efficiencies of 77.6%, 87.1% and 70.4%, respectively. The obtained microalgal biomass (contained 38.5% carbohydrates, 24.9% proteins, 8.8% lipids) was used to co-digest with DW, resulting in good methane production performance. Co-digestion with 25% (w/v) algal biomass obtained a higher CH4 content (65.2%) and production rate (0.16 L/L/d) than other ratios.

17.
J Med Chem ; 66(6): 4086-4105, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36892076

RESUMO

Targeted inhibition of a drug efflux transporter P-glycoprotein (P-gp) is an important strategy to reverse multidrug resistance in cancer chemotherapy. In this study, a rationally structural simplification to natural tetrandrine was performed based on molecular dynamics simulation and fragment growth, leading to an easily prepared, novel, and simplified compound OY-101 with high reversal activity and low cytotoxicity. Its excellent synergistic anti-cancer effect with vincristine (VCR) against drug-resistant cells Eca109/VCR was confirmed by reversal activity assay, flow cytometry, plate clone formation assay, and drug synergism analysis (IC50 = 9.9 nM, RF = 690). Further mechanism study confirmed that the OY-101 was a specific and efficient P-gp inhibitor. Importantly, OY-101 increased VCR sensitization in vivo without obvious toxicity. Overall, our findings may provide an alternative strategy for the design of novel specific P-gp inhibitor as an anti-tumor chemotherapy sensitizer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Neoplasias , Resistencia a Medicamentos Antineoplásicos , Resistência a Múltiplos Medicamentos , Vincristina/farmacologia , Linhagem Celular Tumoral
18.
Artigo em Inglês | MEDLINE | ID: mdl-36881132

RESUMO

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45+ and CD8+ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.

19.
Cell Mol Immunol ; 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864189

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

20.
Materials (Basel) ; 16(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36903149

RESUMO

In this paper, the effects of material removal strategies and initial stress states on the machining deformation of aluminum alloy plates were investigated through a combination of finite element simulation and experiments. We developed different machining strategies described by Tm+Bn, which removal m mm materials form top and n mm materials from the bottom of the plate. The results demonstrate that the maximum deformation of structural components with the T10+B0 machining strategy could reach 1.94 mm, whereas with the T3+B7 machining strategy was only 0.065 mm, decreasing by more than 95%. The asymmetric initial stress state had a significant impact on the machining deformation of the thick plate. The machined deformation of thick plates increased with the increase in the initial stress state. The concavity of the thick plates changed with the T3+B7 machining strategy due to the asymmetry of the stress level. The deformation of frame parts was smaller when the frame opening was facing the high-stress level surface during machining than when it was facing the low-stress level. Moreover, the modeling results for the stress state and machining deformation were accurate and in good accordance with the experimental findings.

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