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1.
Clin Nucl Med ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35020646

RESUMO

ABSTRACT: A 66-year-old man was referred to our hospital due to a newly discovered left chest wall mass, which was diagnosed as plasmacytoma on biopsy. The patient underwent 18F-FDG PET/CT scanning before treatment. PET imaging revealed intense FDG signal in osseous lesions, and the CT showed most of the lesions were osteoblastic. The osseous lesions were predominantly localized to the humerus, femur, tibia, and phalanx of toe.

2.
Cell Death Differ ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022571

RESUMO

Deaths caused by coronavirus disease 2019 (COVID-19) are largely due to the lungs edema resulting from the disruption of the lung alveolo-capillary barrier, induced by SARS-CoV-2-triggered pulmonary cell apoptosis. However, the molecular mechanism underlying the proapoptotic role of SARS-CoV-2 is still unclear. Here, we revealed that SARS-CoV-2 membrane (M) protein could induce lung epithelial cells mitochondrial apoptosis. Notably, M protein stabilized B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) via inhibiting its ubiquitination and promoted BOK mitochondria translocation. The endodomain of M protein was required for its interaction with BOK. Knockout of BOK by CRISPR/Cas9 increased cellular resistance to M protein-induced apoptosis. BOK was rescued in the BOK-knockout cells, which led to apoptosis induced by M protein. M protein induced BOK to trigger apoptosis in the absence of BAX and BAK. Furthermore, the BH2 domain of BOK was required for interaction with M protein and proapoptosis. In vivo M protein recombinant lentivirus infection induced caspase-associated apoptosis and increased alveolar-capillary permeability in the mouse lungs. BOK knockdown improved the lung edema due to lentivirus-M protein infection. Overall, M protein activated the BOK-dependent apoptotic pathway and thus exacerbated SARS-CoV-2 associated lung injury in vivo. These findings proposed a proapoptotic role for M protein in SARS-CoV-2 pathogenesis, which may provide potential targets for COVID-19 treatments.

3.
Nanomedicine ; : 102522, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35032631

RESUMO

We developed surface-enhanced Raman scattering-lateral flow immunoassay (SERS-LFIA) biosensor strips based on SiO2@Au nanoparticles (NPs) for the specific and highly sensitive detection of ricin, staphylococcal enterotoxin B (SEB), and botulinum neurotoxin type A (BoNT/A). SiO2@Au NPs were used to prepare SERS tags with useful properties, such as light weight, uniform particle size, good dispersion, and high SERS performance. The detection limit of the SERS-LFIA strips developed herein for ricin, SEB, and BoNT/A was 0.1, 0.05, and 0.1 ng/mL. Their sensitivity was 100-fold higher than that of colloidal gold-LFIA strips, and the same batch of strips had good repeatability. Moreover, the test was completed within 15 min, indicating that the strips are suitable for the rapid and on-site detection of the said toxins. The SERS-LFIA strips based on SiO2@Au NPs developed herein for the detection of toxins is important to the prevention of bioterrorism attacks.

4.
Nano Today ; 43: 101393, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35035515

RESUMO

There is an urgent need to develop new vaccination strategies to elevate the cross-neutralization against different SARS-CoV-2 strains. In this study, we construct the spherical amantadine-assembled nanostimulator (AAS). Amantadine as immunostimulating molecules are displayed on the outermost layer of AAS. Molecular mechanism analysis reveals that AAS can activate RIG-I-like receptor (RLR) signaling pathway to increase the expression of type I interferons in vivo. AAS-mediated activation of RLR signaling pathway further promotes the maturation and proliferation of dendritic cells (DCs) and T helper cells (Ths), finally activating B cells to produce potent antibody responses. In performance evaluation experiments, the mixture of AAS and dimeric RBD significantly enhances RBD-specific humoral responses (4-fold IgG, 3.5-fold IgG2a, 3.3-fold IgG2b, 3.8-fold IgG3 and 1.3-fold IgM), in comparison to aluminum adjuvant-assistant dimeric RBD. Importantly, AAS dramatically elevates dimeric RBD-elicited cross-neutralization against different SARS-CoV-2 strains such as Wuhan-Hu-1 (9-fold), B.1.1.7 (UK variant, 15-fold), B.1.351 (South African variant, 4-fold) and B.1.617.2 (India variant, 7-fold). Our study verifies the mechanism of AAS in activating RLR signaling pathway in host immune system and highlights the power of AAS in improving antigen-elicited cross-neutralization against different SARS-CoV-2 strains.

5.
Exp Eye Res ; 216: 108946, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35038457

RESUMO

Chemokines and adhesion molecules are major inflammatory mediators of chronic and recurrent vernal keratoconjunctivitis (VKC). Sulforaphane (SFN) is a natural plant extract that is known to have anti-inflammatory and antioxidant properties. SFN is demonstrated to be effective against a variety of human diseases. The current investigation examines the effects and the molecular mechanisms of SFN on cytokine-induced human corneal fibroblasts (HCFs) expression of adhesion molecules and chemokines. HCFs were exposed to both interleukin (IL)-4 and tumor necrosis factor (TNF)-α in the absence or presence of SFN treatment. The levels of thymus- and activation-regulated chemokine (TARC) and eotaxin-1 in culture supernatants were evaluated using enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction analysis (RT-PCR) enabled quantification of mRNA levels of vascular cell adhesion molecule (VCAM)-1, eotaxin-1, and TARC along with cytokine receptors. An immunoblotting assay was used to evaluate the activities of VCAM-1, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), signal transducer and activator of transcription factor (STAT)6 pathways, along with the expression of the cytokine receptors including IL-4 receptor (R)α, IL-13Rα1, TNFRI, as well as TNFRII. SFN inhibited TARC and eotaxin-1 release in HCFs stimulated by TNF-α and IL-4 in a manner dependent on dose and time. SFN suppressed transcriptions of TARC, eotaxin-1, and VCAM-1. Furthermore, the mRNA and protein expression levels of IL-4Rα, TNFRI, and TNFRII were also attenuated by SFN exposure, however, those of IL-13Rα1 remained unaffected. In addition, SFN downregulated the expression of VCAM-1 and the phosphorylation of MAPKs, IκBα, and STAT6. These results suggest that SFN inhibited cytokine-stimulated TARC, eotaxin-1 secretion as well as VCAM-1 expression in HCFs, with these effects likely occurring as a result of cytokine receptor inhibition and attenuation of MAPK, NF-κB, and STAT6 signaling. SFN may therefore have therapeutic potential in VKC treatment.

6.
Chemistry ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34984769

RESUMO

Coinage metal-promoted 5- exo and 6- endo selective cyclization of 2-(1-alkynyl)benzaldimines have been studied. It was found that, under gold catalysis, 2-(1-alkynyl)benzaldimines underwent exclusive 5- exo -dig cyclization processes, followed by oxidation to form N -aryl 3-methyleneisoindolin-1-ones. In contrast, in the presence of base and under activation of AgOTf, switching of 5- exo into 6- endo cyclizations of 2-(1-alkynyl)benzaldimines was observed, exclusively giving N -aryl or N -alkyl substituted isoquinolinium salts. The two key reaction intermediates, exocyclic vinyl-Au and the endocyclic vinyl-Ag species have been isolated and characterized, and the study of their reactivities confirms the plausible mechanisms. Moreover, reacting the resultant 3-methyleneisoindolin-1-ones with benzyne could afford structurally important isoindolinone-based benzocyclobutenes. Additionally, several interesting transformations of the resultant isoquinolinium salts have been also investigated.

7.
Mater Horiz ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985083

RESUMO

The development of high-performance lead-free piezoceramics for replacing Pb-based perovskites has attracted lots of attention, and comparable room-temperature piezoresponse has been realized in (Na,K)NbO3 and BaTiO3-based ceramics with local structure heterogeneity via adjusting polymorphic phase boundary. In this work, a new method of oxygen octahedron tilt design is used in NaNbO3-based lead-free ceramics, which usually shows complex oxygen octahedron tilt information inherited from NaNbO3. The substitution of Ba(Fe0.5Nb0.5)O3 and BaTiO3 with high tolerance factor into NaNbO3 leads to a gradual elimination of anti-parallel cation displacement and anti-phase tilt along the three axes; as a result, a single tetragonal phase with P4bm space group and only in-phase tilt along c axis is achieved in 0.88NaNbO3-0.04Ba(Fe0.5Nb0.5)O3-0.08BaTiO3 ceramic. Accompanying the decreased oxygen octahedral tilt degree, a drastically improved d33 up to 367 pC N-1 (over ten times that of NaNbO3 ceramic) is obtained, reaching a record high in NaNbO3-based lead-free ceramics. Together with temperature insensitive piezoresponse originating from thermally stable oxygen octahedral tilt structure, the studied NaNbO3-based materials show large potential for replacing Pb-based ceramics in some electronic devices. The oxygen octahedron tilt engineering would be used for designing more high-performance lead-free ceramics with high piezoresponse and excellent thermal stability simultaneously.

8.
ACS Nano ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978422

RESUMO

Hypoxia, a common feature of most solid tumors, causes severe tumor resistance to chemotherapy and immunotherapy. Herein, a tumor-acidity and bioorthogonal chemistry-mediated on-site size transformation clustered nanosystem is designed to overcome hypoxic resistance and enhance chemoimmunotherapy. The nanosystem utilized the tumor-acidity responsive group poly(2-azepane ethyl methacrylate) with a rapid response rate and highly efficient bioorthogonal click chemistry to form large-sized aggregates in tumor tissue to enhance accumulation and retention. Subsequently, another tumor-acidity responsive group of the maleic acid amide with a slow response rate was cleaved allowing the aggregates to slowly dissociate into ultrasmall nanoparticles with better tumor penetration ability for the delivery of doxorubicin (DOX) and nitric oxide (NO) to a hypoxic tumor tissue. NO can reverse a hypoxia-induced DOX resistance and boost the antitumor immune response through a reprogrammed tumor immune microenvironment. This tumor-acidity and bioorthogonal chemistry-mediated on-site size transformation clustered nanosystem not only helps to counteract a hypoxia-induced chemoresistance and enhance antitumor immune responses but also provides a general drug delivery strategy for enhanced tumor accumulation and penetration.

9.
Chem Commun (Camb) ; 58(5): 685-688, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34919112

RESUMO

A nano IrxMn(1-x)Oy hybrid electrode with a L12-IrMn3 phase was used as a bifunctional catalyst with ultra-low iridium loading for overall water electrolysis in an acid solution for the first time. The HER activity of the IrxMn(1-x)Oy hybrid electrode not only exceeded that of IrO2, but also exceeded that of Pt/C. The OER activity of the IrxMn(1-x)Oy hybrid electrode also exceeded that of IrO2.

10.
Chemosphere ; 286(Pt 2): 131712, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34333188

RESUMO

This work focuses on the thermally induced variation in the nanostructure, size of primary particles and oxidative reactivity of diesel soot and a commercial carbon black in an inert gas environment at temperatures ranging from 600 to 1000 °C. Soot nanostructure and size were characterized by high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The soot reactivity was evaluated with respect to activation energy (Ea) and characteristic oxidation temperature, including peak temperature (TP) and burnout temperature (Tb), using thermogravimetric analysis (TGA). The mass loss of diesel soot and carbon black rises when increasing the thermal treatment temperature, especially at 1000 °C, and a significant quantity of mass loss can be observed, which is primarily due to thermal fragmentation and the desorption of chemical species on soot surfaces. The HRTEM and XRD results all indicate that the thermally treated soot samples have more ordered nanostructure than the untreated samples. There is a reduction in the size of primary particles as thermal treatment temperature increases. The soot reactivity decreases after thermal treatment, as manifested by the elevation in Ea, TP, and Tb values. Moreover, the oxidation reactivity of soot samples is closely associated with the fringe length, tortuosity, and fringe tortuosity. Compared to carbon black, diesel soot with a more disorder structure has a higher oxidative reactivity.


Assuntos
Nanoestruturas , Fuligem , Microscopia Eletrônica de Transmissão , Oxirredução , Emissões de Veículos/análise
12.
Angew Chem Int Ed Engl ; : e202116208, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34964224

RESUMO

Polyhydroxyalkanoates (PHAs) are a unique class of commercially manufactured biodegradable polyesters with properties suitable for partially substituting petroleum-based plastics. However, high costs and low volumes of production have restricted their application as commodity materials. In this study, tri-metallic complexes were developed for carbonylative polymerization via a dual catalysis strategy, and 17 products of novel PHAs with up to 38.2 kg mol-1 Mn values were discovered. The polymerization proceeds in a sequential fashion, which entails the carbonylative ring expansion of epoxide to ß-lactone and its subsequent ring-opening polymerization that occurs selectively at the O-alkyl bond via carboxylate species. The wide availability and structural diversity of epoxide monomers provide PHAs with various structures, excellent functionalities, and tunable properties. This study represents a rare example of the preparation of PHAs using epoxides and carbon monoxide as raw materials.

13.
Cell Death Discov ; 7(1): 387, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907204

RESUMO

Emerging studies have found long noncoding RNAs, widely expressed in eukaryotes, crucial regulators in the progression of human cancers, including hepatocellular carcinoma (HCC). Although the long intergenic noncoding RNA 667 (LINC00667) can promote the progression of a variety of cancer types, the expression pattern, the role in cancer progression, and the molecular mechanism involved in HCC remain unclear. This study aims to investigate the function and mechanism of LINC00667 in HCC progression. The effects of LINC00667 silencing in cell proliferation, cell migration, and cell invasion, and androgen receptor (AR) expression were determined with loss-of-function phenotypic analysis in Huh-7 and HCCLM3 cells, and subsequently testified in vivo in tumor growth. We found that the expression of LINC00667 was upregulated in HCC tissues and cell lines. Upregulation of LINC00667 was significantly associated with the unfavorable prognosis of HCC in our study patients. On the other hand, low expression of LINC00667 significantly inhibited the cell proliferation, cell migration and cell invasion of HCC in vitro and tumor growth in vivo. This inhibitory effect could be counteracted by miR-130a-3p inhibitor. LINC00667 reduced the inhibition of AR expression by miR-130a-3p, which correlated with the progression of HCC. Our finding suggests LINC00667 is a molecular sponge in the miR-130s-3p/AR signal pathway in the progression of HCC, in which it relieves the repressive function of miR-130a-3p on the AR expression. This indicates LINC00667 functions as a tumor promotor in promoting HCC progression through targeting miR-130a-3p/AR axis, making a novel biomarker and potential therapeutic target for HCC.

14.
Planta Med ; 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963184

RESUMO

Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C-D (1-2), together with two known congeners (3-4), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL sensitivity of 1-4 in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1-4 at 50 µM with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1-4 alone.

15.
Ann Transl Med ; 9(21): 1631, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34926675

RESUMO

Coronavirus disease 2019 (COVID-19) has threatened human health worldwide and could lead to multiple organs injury. However, the impact on the virus infecting the biliary system, especially the gallbladder, has remained unclear and no pathological evidence has been reported yet. A case of SARS-CoV-2 infection in a gallbladder with cholecystitis, which progressed rapidly to sepsis and required an emergency operation was investigated and reported. Clinical specimens of the COVID-19 patient including serum, oropharyngeal swabs, sputum, bile, abdominal drainage fluid, urine, stool, and gallbladder tissue were collected and tested for SARS-CoV-2 RNA using a quantitative polymerase chain reaction (qPCR) assay. Fresh normal gallbladder tissue and gangrenous gallbladder tissue were also collected for further research including hematoxylin and eosin (HE), immunohistochemistry (IHC), and immunofluorescent (IF) staining, and compared with the gallbladder from the COVID-19 patient. The bile, as well as the serum, oropharyngeal swabs, sputum, abdominal drainage fluid, urine, and rectal swabs were consecutively negative for SARS-CoV-2 RNA. The viral host receptor angiotensin-converting enzyme 2 (ACE2) was highly expressed in gallbladder epithelial cells, and viral nucleocapsid protein (NP) was visualized in the cytoplasm of gallbladder epithelial cells. Immune cells including CD2, CD3, CD4, CD8, CD20, CD38, CD68, and MPO were positive in gangrenous gallbladder tissues without SARS-CoV-2 infection, and were relatively downregulated in SARS-CoV-2 infective gallbladder tissue. This study provided evidence of SARS-CoV-2 infection in the gallbladder and verified that the gallbladder was one of the target organs that SARS-CoV-2 could attack and damage using ACE2 as a cell receptor. Due to the immune dysregulation involved, more vigilant management and early assessment is needed for COVID-19 patients with the comorbidity of cholecystitis.

16.
Viruses ; 13(12)2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34960730

RESUMO

Novel therapeutic strategies aiming at the permanent inactivation of the HIV-1 reservoir in infected individuals are currently being explored, including approaches based on CRISPR-Cas gene editing. Extinction of all infectious HIV provirus in infected T-cell cultures was previously achieved when cells were transduced with lentiviral vectors for the stable expression of CRISPR-Cas9 or Cas12a systems targeting HIV DNA. Because lentiviral transduction and long-term CRISPR-Cas activity are less suitable for in vivo application of this antiviral strategy, we investigated whether HIV can also be completely inactivated by transient CRISPR-Cas activity. Latently infected SupT1 T-cells were repeatedly transfected with different Cas9 and Cas12a mRNA/protein sources in combination with dual gRNAs/crRNAs targeting highly conserved viral sequences. Upon repeated Cas9 protein treatment, viral replication could no longer be reactivated. We demonstrate that this was due to complete mutational inactivation of the proviral DNA, mostly through mutations at the target sites, but also through excision or inversion of the viral DNA fragment between the two target sites. These results demonstrate that repeated transient CRISPR-Cas treatment of a latently infected T-cell culture can lead to the permanent inactivation of HIV replication, indicating that transient CRISPR-Cas delivery methods can be considered for in vivo application.

17.
Bioresour Technol ; 346: 126610, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34954360

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) have led to failure of waste water treatment plant operations. In this study, a two-sludge system was used to solve this problem of simultaneously removing phosphorus, nitrogen, and PAHs. The results showed that increasing the maximum PAHs concentration to 15 mg/L did not have any negative effect on the removal rates of total nitrogen (79.68%) and chemical oxygen demand (75.94%); however, the phosphorus removal efficiency decreased to 61.16%. The system exhibited a stronger degradation ability for phenanthrene. Thauera, Hydrogenophaga, and Hyphomicrobium were enriched, which resulted in good denitrification, and contributed to PAHs removal. PAHs mixture promoted PAHs functional genes but restrained denitrification functional genes. However, single naphthalene enhanced denitrification functional genes, which confirmed the feasibility of denitrification coupled with PAHs degradation. In conclusion, for the removal of pollutants from sewage treatment, nitrogen and phosphorus removal coupled with PAHs could be maintained by selecting a two-sludge system.

18.
Cell Death Dis ; 12(11): 1052, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741044

RESUMO

STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.

19.
Front Endocrinol (Lausanne) ; 12: 744868, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721299

RESUMO

Diabetic foot ulcer (DFU) is a combination of neuropathy and various degrees of peripheral vasculopathy in diabetic patients resulting in lower extremity infection, ulcer formation, and deep-tissue necrosis. The difficulty of wound healing in diabetic patients is caused by a high glucose environment and various biological factors in the patient. The patients' skin local microenvironment changes and immune chemotactic response dysfunction. Wounds are easy to be damaged and ulcerated repeatedly, but difficult to heal, and eventually develop into chronic ulcers. DFU is a complex biological process in which many cells interact with each other. A variety of growth factors released from wounds are necessary for coordination and promotion of healing. Fibroblast growth factor (FGF) is a family of cell signaling proteins, which can mediate various processes such as angiogenesis, wound healing, metabolic regulation and embryonic development through its specific receptors. FGF can stimulate angiogenesis and proliferation of fibroblasts, and it is a powerful angiogenesis factor. Twenty-three subtypes have been identified and divided into seven subfamilies. Traditional treatments for DFU can only remove necrotic tissue, delay disease progression, and have a limited ability to repair wounds. In recent years, with the increasing understanding of the function of FGF, more and more researchers have been applying FGF-1, FGF-2, FGF-4, FGF-7, FGF-21 and FGF-23 topically to DFU with good therapeutic effects. This review elaborates on the recently developed FGF family members, outlining their mechanisms of action, and describing their potential therapeutics in DFU.

20.
Front Oncol ; 11: 733680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722278

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.

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