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1.
Ecotoxicol Environ Saf ; 228: 112986, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34794021

RESUMO

OBJECTIVE: This study aimed to examine the relationships among N, N-dimethylformamide (DMF) exposure, cytochrome P4502E1 (CYP2E1) single nucleotide polymorphisms (SNPs) (rs2031920, rs3813867, rs6413432), transmembrane 6 superfamily member 2 (TM6SF2) SNP rs58542926 and non-alcoholic fatty liver disease (NAFLD). METHODS: Baseline data were collected from participants who were then followed for 5 years in a prospective cohort study. The cohort initially consisted of 802 workers and ultimately included 660 people, all of whom underwent annual occupational health examinations from 2010 to 2015. RESULTS: The above-threshold group (≥7.3 mg/m³ adjusted relative risk (RR)= 3.620, 95%CI 2.072-6.325) was significantly more likely to develop NAFLD than the below-threshold group (<7.3 mg/m³). The TM6SF2 SNP rs58542926 CT (adjusted RR=3.921, 95% CI 2.329-6.600, P = 0.000) and CT+TT (adjusted RR=4.385, 95% CI 2.639-7.287, P = 0.000) genotypes were risk factors for NAFLD, as compared with the TM6SF2 rs58542926 CC genotype. Each dose group (below-threshold group and above-threshold group) interacting with the genotype of TM6SF2 SNP rs58542926 had an adjusted RR from 7.764 (95% CI 3.272-18.420, P = 0.000) to 24.022 (95% CI 8.971-64.328, P = 0.000). The T allele of rs58542926 in the TM6SF2 gene may be a risk factor for susceptibility to DMF-induced NAFLD. CONCLUSION: Polymorphisms of TM6SF2 SNP rs58542926 may play an important role in susceptibility to NAFLD after exposure to DMF.

2.
Oxid Med Cell Longev ; 2021: 7301373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777693

RESUMO

Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated ß-galactosidase (SA-ß-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-κB) p65 (Lys310), p21 Waf1/Cip1 , and p16 Ink4a and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming γ-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-κB p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.

3.
Chemistry ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34651354

RESUMO

Nonlinear optical (NLO) crystals are widely applied in information technology, micro-manufacturing and medical treatment. Herein, a new lead mixed halide with strong second-harmonic generation (SHG) response, Cs3 Pb2 (CH3 COO)2 Br3 I2 , has been designed and rationally synthesized. Cs3 Pb2 (CH3 COO)2 Br3 I2 represents the rare NLO crystal featuring that three different anions (I- , Br- and O2- ) simultaneously coordinate the Pb(II) atom to form a severely distorted [PbBr2 I2 O2 ] polyhedron with a large polarizability. Remarkably, Cs3 Pb2 (CH3 COO)2 Br3 I2 not only exhibits a very strong phase-matching SHG response of 9×KH2 PO4 (KDP), but also possesses a large birefringence (0.27@1064 nm) and high laser damage threshold (LDT). The strong SHG effect of Cs3 Pb2 (CH3 COO)2 Br3 I2 mainly originates from the oriented arrangement of [Pb2 Br3 I2 ] chains. This study points out an effective strategy to develop new NLO crystals with strong SHG response.

4.
Adv Mater ; : e2107206, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676919

RESUMO

2D materials have been attracting high interest in recent years due to their low structural symmetry, excellent photoresponse, and high air stability. However, most 2D materials can only respond to specific light, which limits the development of wide-spectrum photodetectors. Proper bandgap and the regulation of Fermi level are the foundations for realizing electronic multichannel transition, which is an effective method to achieve a wide spectral response. Herein, a noble 2D material, palladium phosphide sulfide (PdPS), is designed and synthesized. The bandgap of PdPS is around 2.1 eV and the formation of S vacancies, interstitial Pd and P atoms promote the Fermi level very close to the conduction band. Therefore, the PdPS-based photodetector shows impressive wide spectral response from solar-blind ultraviolet to near-infrared based on the multichannel transition. It also exhibits superior optoelectrical properties with photoresponsivity (R) of 1 × 103 A W-1 and detectivity (D*) of 4 × 1011 Jones at 532 nm. Moreover, PdPS exhibits good performance of polarization detection with dichroic ratio of ≈3.7 at 808 nm. Significantly, it achieves polarimetric imaging and hidden-target detection in complex environments through active detection.

5.
Front Oncol ; 11: 642018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540655

RESUMO

Objective: This work aims to analyze the 100 most cited papers in radiotherapy or chemoradiotherapy for cervical cancer. Methods: The 100 most cited papers in radiotherapy or chemoradiotherapy between 1990 and 2020 were identified with Thompson Reuters Web of Science citation indexing on August 24, 2020. The publication years, source titles, countries/regions, total citations, and average citations per year were extracted from the Web of Science. The research type and research domain were classified by the authors. Results: These 100 papers were cited a total of 28,714 times, and the median number of citations was 169.5 (ranging from 116 to 1,700 times). The most cited paper was "Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer" by Rose et al., with a total citation of 1,700 times. The International Journal of Radiation Oncology Biology Physics (40 papers), Radiotherapy and Oncology (14 papers), and the Journal of Clinical Oncology (12 papers) published the largest number of papers. USA (47 papers), Austria (18 papers), Canada (13 papers), and England (13 papers) contributed the largest number of papers. Image-guided adaptive brachytherapy (IGABT) had the largest number of papers (25 papers). Concurrent chemotherapy was the most cited research domain, with 10,663 total citations and 592.4 citations per paper. Conclusion: In the present study, we conducted a bibliometric analysis of the 100 most cited papers in radiotherapy or concurrent chemoradiotherapy for cervical cancer in the past 30 years. IGABT and concurrent chemotherapy were the most cited research domains.

6.
Genomics ; 113(6): 3735-3749, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517091

RESUMO

Germination and seedling growth are crucial for plant development and agricultural production. While, the regulatory mechanisms during these processes in Tibetan hulless barley (Hordeum vulgare L. var. nudum) are not well understood. Given the regulatory roles of microRNAs (miRNAs) in crop plants and the irreplaceability of barley in the highland area of China, we herein presented a genome-wide survey of miRNAs to reveal a potential regulatory network in the early developmental stages of two Tibetan hulless barleys, from which a total of 156 miRNAs was identified including 35 known and 121 novel ones. Six of the identified novel miRNAs were further experimentally validated. According to the evolutionary analysis, miR156, miR166, miR168, and miR171 were conserved across Tibetan hulless barleys and eight other seed plants. Expression profiles of ten known miRNAs showed that they were involved in phytohormone signaling, carbohydrate and lipid metabolism, as well as juvenile-adult transition during barley development. Moreover, a total of 1280 genes targeted by 101 miRNAs were predicted from both barley libraries. Three genes (PLN03212, MATE eukaryotic, and GRAS) were validated via the RNA ligase-mediated 5'-rapid amplification of cDNA ends (RLM-5' RACE) to be the targets of hvu-miR159a, hvu-miR166a, and hvu-miR171-3p, respectively. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of putative targets, the most abundant pathways were related to "metabolism". These results revealed that miRNA-target pairs participating in the regulation of multigene expression and the embryonic development of Tibetan hulless barleys were controlled by complex mechanisms involving the concordant expression of different miRNAs and feedback loops among miRNAs as well as their targets. The study provides insight into the regulatory network of barley miRNAs for better understanding of miRNA functions during germination and seedling growth.

7.
IEEE Trans Med Imaging ; PP2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398751

RESUMO

Unsupervised domain adaptation (UDA) methods have shown their promising performance in the cross-modality medical image segmentation tasks. These typical methods usually utilize a translation network to transform images from the source domain to target domain or train the pixel-level classifier merely using translated source images and original target images. However, when there exists a large domain shift between source and target domains, we argue that this asymmetric structure, to some extent, could not fully eliminate the domain gap. In this paper, we present a novel deep symmetric architecture of UDA for medical image segmentation, which consists of a segmentation sub-network, and two symmetric source and target domain translation sub-networks. To be specific, based on two translation sub-networks, we introduce a bidirectional alignment scheme via a shared encoder and two private decoders to simultaneously align features 1) from source to target domain and 2) from target to source domain, which is able to effectively mitigate the discrepancy between domains. Furthermore, for the segmentation sub-network, we train a pixel-level classifier using not only original target images and translated source images, but also original source images and translated target images, which could sufficiently leverage the semantic information from the images with different styles. Extensive experiments demonstrate that our method has remarkable advantages compared to the state-of-the-art methods in three segmentation tasks, i.e., cross-modality cardiac, BraTS, and abdominal multi-organ segmentation.

8.
J Environ Manage ; 298: 113499, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385115

RESUMO

The pollution control of local government to industrial enterprises is actually a long-term, complex and dynamic game process. This study develops an evolutionary game model to analyze the operation mechanism of local governments' different expenditure preferences on the production behavior of industrial polluting enterprises, so as to specify the behavioral characteristics and optimal strategy of local environmental governance. The results indicated that whether the relationship between local governments and polluting enterprises in environmental governance becomes cooperative or collusive depends on their game sequence and initial endowment. Under the condition of realizing a steady state of cooperation, polluting enterprises would advance faster toward clean production if local governments distribute more environmental expenditures on cost subsidies for enterprises to implement clean production. The findings of this study provide decision-making basis for local governments to control industrial pollution.


Assuntos
Política Ambiental , Governo Local , China , Conservação dos Recursos Naturais , Poluição Ambiental/prevenção & controle , Governo , Indústrias
9.
Luminescence ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432356

RESUMO

A chemiluminescence (CL) sensor array was developed based on 11 CL systems cross-combined by three luminescence reagents and four oxidants. Using the CL sensor array, we measured seven toxicants, including morphine, ketamine, diazepam, chlorpromazine, strychnine, paraquat, and fenpropathrin, which represent psychotropic drugs, sedatives and hypnotics, rodenticides, herbicides, and insecticides, respectively. The CL response pattern or 'fingerprints' were obtained for a given compound on the sensor array and then discriminated through principal component analysis. The established sensor array has been applied to real-life samples and the results showed that it possesses excellent discrimination.

10.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206763

RESUMO

Acute pancreatitis (AP) is an inflammatory disorder, involving acinar cell death and the release of inflammatory cytokines. Currently, there are limited effective therapeutic agents for AP. Betulinic acid (BA) is a pentacyclic triterpenoid extracted from Betula platyphylla that has been shown to have anti-inflammatory effects. In this study, we aimed to investigate the effects of BA on AP and elucidate the potential underlying mechanisms. AP was induced in mice through six intraperitoneal injections of cerulein. After the last cerulein injection, the mice were sacrificed. Our results revealed that pre- and post-treatment with BA significantly reduced the severity of pancreatitis, as evidenced by a decrease in histological damage in the pancreas and lung, serum amylase and lipase activity and pancreatic myeloperoxidase activity. Furthermore, BA pretreatment reduced proinflammatory cytokine production, augmentation of chemokines, and infiltration of macrophages and neutrophils in the pancreas of AP mice. In addition, mice that were pretreated with BA showed a reduction in Iκ-Bα degradation and nuclear factor-kappa B (NF-κB) binding activity in the pancreas. Moreover, BA reduced the production of proinflammatory cytokines and NF-κB activation in pancreatic acinar cells (PACs). These findings suggest that BA may have prophylactic and therapeutic effects on AP via inhibition of the NF-κB signaling pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , NF-kappa B/metabolismo , Pancreatite/tratamento farmacológico , Triterpenos Pentacíclicos/uso terapêutico , Amilases/sangue , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Lipase/sangue , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Triterpenos Pentacíclicos/farmacologia , Peroxidase/metabolismo , Transdução de Sinais
11.
ACS Appl Mater Interfaces ; 13(27): 32579-32589, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34196522

RESUMO

A perpendicularly magnetized spin injector with a high Curie temperature is a prerequisite for developing spin optoelectronic devices on two-dimensional (2D) materials working at room temperature (RT) with zero applied magnetic field. Here, we report the growth of Ta/CoFeB/MgO structures with large perpendicular magnetic anisotropy (PMA) on full-coverage monolayer (ML) molybdenum disulfide (MoS2). A large perpendicular interface anisotropy energy of 0.975 mJ/m2 has been obtained at the CoFeB/MgO interface, comparable to that observed in magnetic tunnel junction systems. It is found that the insertion of MgO between the ferromagnetic (FM) metal and the 2D material can effectively prevent the diffusion of the FM atoms into the 2D material. Moreover, the MoS2 ML favors a MgO(001) texture and plays a critical role in establishing the large PMA. First-principles calculations on a similar Fe/MgO/MoS2 structure reveal that the MgO thickness can modify the MoS2 band structure, from a direct band gap with 3ML-MgO to an indirect band gap with 7 ML-MgO. The proximity effect induced by Fe results in splitting of 10 meV in the valence band at the Γ point for the 3ML-MgO structure, while it is negligible for the 7 ML-MgO structure. These results pave the way to develop RT spin optoelectronic devices based on 2D transition-metal dichalcogenide materials.

12.
Chemistry ; 27(51): 12976-12980, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34258801

RESUMO

The discovery of new nonlinear optical (NLO) crystals with excellent properties is in urgently demand because of their ability to generate coherent light. Herein, we report an unique NLO lead bromide formate, KCs2 [Pb2 Br5 (HCOO)2 ], which has been synthesized by a mix-solvothermal method. KCs2 [Pb2 Br5 (HCOO)2 ] exhibits strong phase-matching second-harmonic generation (SHG) response (6.5×KDP), large birefringence (0.16@ 1064 nm), and a wide transparent window in most visible light and mid-IR region. Interestingly, KCs2 [Pb2 Br5 (HCOO)2 ] features a polar 3D lead-bromide framework in which adjacent Pb-Br layers containing coplanar Pb6 Br6 rings are not only parallel to each other, but also orient in the same direction. These oriented arrangements are responsible for the strong SHG response and large birefringence that are elucidated by both local dipole moment and theoretical calculations. This research provides a new strategy to explore subsequent NLO crystals.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34061743

RESUMO

When designing infographics, general users usually struggle with getting desired color palettes using existing infographic authoring tools, which sometimes sacrifice customizability, require design expertise, or neglect the influence of elements? spatial arrangement. We propose a data-driven method that provides flexibility by considering users? preferences, lowers the expertise barrier via automation, and tailors suggested palettes to the spatial layout of elements. We build a recommendation engine by utilizing deep learning techniques to characterize good color design practices from data, and further develop InfoColorizer, a tool that allows users to obtain color palettes for their infographics in an interactive and dynamic manner. To validate our method, we conducted a comprehensive four-part evaluation, including case studies, a controlled user study, a survey study, and an interview study. The results indicate that InfoColorizer can provide compelling palette recommendations with adequate flexibility, allowing users to effectively obtain high-quality color design for input infographics with low effort.

14.
Res Sq ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34100010

RESUMO

Artificial intelligence (AI) methods for the automatic detection and quantification of COVID-19 lesions in chest computed tomography (CT) might play an important role in the monitoring and management of the disease. We organized an international challenge and competition for the development and comparison of AI algorithms for this task, which we supported with public data and state-of-the-art benchmark methods. Board Certified Radiologists annotated 295 public images from two sources (A and B) for algorithms training (n=199, source A), validation (n=50, source A) and testing (n=23, source A; n=23, source B). There were 1,096 registered teams of which 225 and 98 completed the validation and testing phases, respectively. The challenge showed that AI models could be rapidly designed by diverse teams with the potential to measure disease or facilitate timely and patient-specific interventions. This paper provides an overview and the major outcomes of the COVID-19 Lung CT Lesion Segmentation Challenge - 2020.

15.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34099577

RESUMO

Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV-infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV.


Assuntos
Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Zoonoses/virologia , África , Animais , Arábia , Linhagem Celular , Dipeptidil Peptidase 4/metabolismo , Técnicas de Introdução de Genes , Humanos , Cinética , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Fenótipo , Filogenia , Glicoproteína da Espícula de Coronavírus/metabolismo , Replicação Viral/fisiologia
16.
Adv Sci (Weinh) ; 8(14): e2100075, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34021718

RESUMO

With the increasing demand for detection accuracy and sensitivity, dual-band polarimetric image sensor has attracted considerable attention due to better object recognition by processing signals from diverse wavebands. However, the widespread use of polarimetric sensors is still limited by high noise, narrow photoresponse range, and low linearly dichroic ratio. Recently, the low-dimensional materials with intrinsic in-plane anisotropy structure exhibit the great potential to realize direct polarized photodetection. Here, strong anisotropy of 1D layered bismuth sulfide (Bi2 S3 ) is demonstrated experimentally and theoretically. The Bi2 S3 photodetector exhibits excellent device performance, which enables high photoresponsivity (32 A W-1 ), Ion /Ioff ratio (1.08 × 104 ), robust linearly dichroic ratio (1.9), and Hooge parameter (2.0 × 10-5 at 1 Hz) which refer to lower noise than most reported low-dimensional materials-based devices. Impressively, such Bi2 S3 nanowire exhibits a good broadband photoresponse, ranging from ultraviolet (360 nm) to short-wave infrared (1064 nm). Direct polarimetric imaging is implemented at the wavelengths of 532 and 808 nm. With these remarkable features, the 1D Bi2 S3 nanowires show great potential for direct dual-band polarimetric image sensors without using any external optical polarizer.

17.
ACS Appl Mater Interfaces ; 13(13): 15709-15719, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33755430

RESUMO

Natural intervertebral disks (IVDs) exhibit distinctive anisotropic mechanical support and dissipation performances due to their well-developed special microstructures. As the intact IVD structure degrades, the absence of function will lead to severe backache. However, the complete simulation for the characteristic structure and function of native IVD is unattainable using current methods. In this work, by overall construction of the two-phase structure of native IVD (extraction of the naturally aligned cellulose framework and in situ polymerization of the nanocomposite hydrogel), a complete wood framework IVD (WF-IVD) is manufactured containing elastic nanocomposite hydrogel-based nucleus pulposus (NP) and anisotropic wood cellulose hydrogel-based annulus fibrosus (AF). In addition to the imitation and construction of the natural structure, WF-IVD also achieves favorable mechanical matching and good biocompatibility and possesses unique mechanical buckling buffer characteristics owing to the aligned fiber bundles. This study offers a promising strategy for the mimicking and construction of complex native tissues.


Assuntos
Materiais Biomiméticos/química , Celulose/química , Hidrogéis/química , Disco Intervertebral/química , Tecidos Suporte/química , Animais , Anisotropia , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Biomimética , Tampões (Química) , Linhagem Celular , Fagus/química , Disco Intervertebral/citologia , Células-Tronco Mesenquimais/citologia , Camundongos , Engenharia Tecidual/métodos , Madeira/química
18.
Hepatology ; 73(5): 1717-1735, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33682185

RESUMO

BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) are key players in multicellular, stromal-dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor-associated neutrophils (TANs) during different stages of HCC pathogenesis. APPROACH AND RESULTS: In the HCC-TME, CAF-derived cardiotrophin-like cytokine factor 1 (CLCF1) increased chemokine (C-X-C motif) ligand 6 (CXCL6) and TGF-ß secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGF-ß secreted by HCC cells activated extracellular signal-regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1-mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up-regulation of the CLCF1-CXCL6/TGF-ß axis exhibited a marked correlation with increased cancer stem cells, "N2"-polarized TANs, tumor stage, and poor prognosis. CONCLUSIONS: This study reveals a cytokine-mediated cellular crosstalk and clinical network involving the CLCF1-CXCL6/TGF-ß axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.

19.
Clin Transl Immunology ; 10(3): e1257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717483

RESUMO

Objectives: Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab-activated autologous dendritic cells-co-cultured cytokine-induced killer cells in patients with advanced RCC. Methods: All adult patients, including treatment-naive or pretreated with VEGF-targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab-activated dendritic cells-co-cultured cytokine-induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results: The 43 patients (22 untreated and 21 previously treated) showed a median progression-free survival (mPFS) of 14.7 months (95% CI, 11.16-18.30). mPFS in treatment-naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log-rank P-value = 0.07). Overall response rates were 25.6% (95% CI, 13.5-41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar-plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long-term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum-level immunostimulatory cytokine profile. Conclusions: The combination therapy was active and well tolerated for treatment of advanced RCC, either as first- or second-line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.

20.
Int J Mol Sci ; 22(3)2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33572597

RESUMO

Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus that has been used as an anti-inflammatory agent in various pathological models. However, the renal protective activity of loganin remains unclear. In this study, to examine the protective effect of loganin on cisplatin-induced AKI, male C57BL/6 mice were orally administered with loganin (1, 10, and 20 mg/kg) 1 h before intraperitoneal injection of cisplatin (10 mg/kg) and sacrificed at three days after the injection. The administration of loganin inhibited the elevation of blood urea nitrogen (BUN) and creatinine (CREA) in serum, which are used as biomarkers of AKI. Moreover, histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during AKI. Taken together, our results suggest that loganin may attenuate cisplatin-induced AKI through the inhibition of ERK1/2.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Cisplatino/efeitos adversos , Iridoides/administração & dosagem , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Morte Celular/efeitos dos fármacos , Creatinina/sangue , Citocinas/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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