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1.
Sci Adv ; 10(10): eadk9485, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38446879

RESUMEN

Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer-expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.


Asunto(s)
Melaninas , Fármacos Fotosensibilizantes , Animales , Ratones , Fármacos Fotosensibilizantes/farmacología , Fototerapia , Bacterias , Rayos Infrarrojos
2.
Molecules ; 29(5)2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38474648

RESUMEN

Currently, the alteration of external factors during crude oil extraction easily disrupts the thermodynamic equilibrium of asphaltene, resulting in the continuous flocculation and deposition of asphaltene molecules in crude oil. This accumulation within the pores of reservoir rocks obstructs the pore throat, hindering the efficient extraction of oil and gas, and consequently, affecting the recovery of oil and gas resources. Therefore, it is crucial to investigate the principles of asphaltene deposition inhibition and the synthesis of asphaltene inhibitors. In recent years, the development of nanotechnology has garnered significant attention due to its unique surface and volume effects. Nanoparticles possess a large specific surface area, high adsorption capacity, and excellent suspension and catalytic abilities, exhibiting unparalleled advantages compared with traditional organic asphaltene inhibitors, such as sodium dodecyl benzene sulfonate and salicylic acid. At present, there are three primary types of nanoparticle inhibitors: metal oxide nanoparticles, organic nanoparticles, and inorganic nonmetal nanoparticles. This paper reviews the recent advancements and application challenges of nanoparticle asphaltene deposition inhibition technology based on the mechanism of asphaltene deposition and nano-inhibitors. The aim was to provide insights for ongoing research in this field and to identify potential future research directions.

3.
NPJ Vaccines ; 9(1): 22, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310094

RESUMEN

Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB.

4.
Immunology ; 172(2): 181-197, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38269617

RESUMEN

Immune system imbalances contribute to the pathogenesis of several different diseases, and immunotherapy shows great therapeutic efficacy against tumours and infectious diseases with immune-mediated derivations. In recent years, molecules targeting the programmed cell death protein 1 (PD-1) immune checkpoint have attracted much attention, and related signalling pathways have been studied clearly. At present, several inhibitors and antibodies targeting PD-1 have been utilized as anti-tumour therapies. However, increasing evidence indicates that PD-1 blockade also has different degrees of adverse side effects, and these new explorations into the therapeutic safety of PD-1 inhibitors contribute to the emerging concept that immune normalization, rather than immune enhancement, is the ultimate goal of disease treatment. In this review, we summarize recent advancements in PD-1 research with regard to immune normalization and targeted therapy.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Animales , Inmunoterapia/métodos , Transducción de Señal/efectos de los fármacos , Terapia Molecular Dirigida
5.
Int J Mol Sci ; 24(19)2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37834070

RESUMEN

The genus Apium, belonging to the family Apiaceae, comprises roughly 20 species. Only two species, Apium graveolens and Apium leptophyllum, are available in China and are both rich in nutrients and have favorable medicinal properties. However, the lack of genomic data has severely constrained the study of genetics and evolution in Apium plants. In this study, Illumina NovaSeq 6000 and Nanopore sequencing platforms were employed to identify the mitochondrial genomes of A. graveolens and A. leptophyllum. The complete lengths of the mitochondrial genomes of A. graveolens and A. leptophyllum were 263,017 bp and 260,164 bp, respectively, and contained 39 and 36 protein-coding genes, five and six rRNA genes, and 19 and 20 tRNA genes. Consistent with most angiosperms, both A. graveolens and A. leptophyllum showed a preference for codons encoding leucine (Leu). In the mitochondrial genome of A. graveolens, 335 SSRs were detected, which is higher than the 196 SSRs found in the mitochondrial genome of A. leptophyllum. Studies have shown that the most common RNA editing type is C-to-U, but, in our study, both A. graveolens and A. leptophyllum exhibited the U-C editing type. Furthermore, the transfer of the mitochondrial genomes of A. graveolens and A. leptophyllum into the chloroplast genomes revealed homologous sequences, accounting for 8.14% and 4.89% of the mitochondrial genome, respectively. Lastly, in comparing the mitochondrial genomes of 29 species, it was found that A. graveolens, A. leptophyllum, and Daucus carota form a sister group with a support rate of 100%. Overall, this investigation furnishes extensive insights into the mitochondrial genomes of A. graveolens and A. leptophyllum, thereby enhancing comprehension of the traits and evolutionary patterns within the Apium genus. Additionally, it offers supplementary data for evolutionary and comparative genomic analyses of other species within the Apiaceae family.


Asunto(s)
Apiaceae , Apium , Daucus carota , Genoma del Cloroplasto , Genoma Mitocondrial , Magnoliopsida , Filogenia , Apium/genética , Genoma Mitocondrial/genética , Apiaceae/genética , Daucus carota/genética , Magnoliopsida/genética
6.
Inorg Chem ; 62(23): 9111-9119, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37262419

RESUMEN

Here, we synthesized pure Cs3Bi2Cl9 (CBC) and manganese (Mn)-doped crystals with different feeding ratios, leading to changes in structure and luminescence. The crystals Cs3Bi2Cl9-Mn (CBCM) formed by doping a minor amount of Mn2+ (Bi/Mn = 8:1) maintain the orthorhombic phase structure of the host, but when Bi/Mn = 2:1, the crystal structure is more inclined to form Cs4MnBi2Cl12 (CMBC) of a trigonal phase. Combined with density functional theory (DFT) calculation, the results demonstrate that a moderate amount of Mn2+ doping can create impurity energy levels in the forbidden band. However, as the structure transitions, the type of energy band structure changes from indirect to direct, with completely different electronic orbital features. Temperature-dependent time-resolved and steady-state photoluminescence spectroscopies are used to explore the structure-related thermal properties and transitional process. Differences energy transfer routes are revealed, with CBCM relying on intersystem energy transfer and CMBC mainly depending on direct excitation of Mn2+ to produce d-d transitions. Furthermore, since CMBC is temperature-sensitive, we perform the first photoluminescent (PL) lifetime temperature measurement using CBMC and obtain a maximum relative sensitivity of 1.7 %K-1 and an absolute sensitivity of 0.0099 K-1. Our work provides insight into the mechanism of Mn2+ doping-induced luminescence and offers a potentially effective doping strategy for improving the PL properties of lead-free metal halide perovskites.

7.
Oncoimmunology ; 11(1): 2010894, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36524206

RESUMEN

Hepatocellular carcinoma (HCC) is associated with a high mortality rate and presents a major challenge for human health. Activation of multiple oncogenes has been reported to be strongly associated with the progression of HCC. Moreover, the immunosuppressive tumor microenvironment (TME) and the host immune system are also implicated in the development of malignant HCC tumors. Glypican-3 (GPC-3), a proteoglycan involved in the regulation of cell proliferation and apoptosis, is aberrantly expressed in HCC. We synthesized a short 5'-triphosphate (3p) RNA targeting GPC-3, 3p-GPC-3 siRNA, and found that it effectively inhibited subcutaneous HCC growth by raising type I IFN levels in tumor cells and serum and promoting tumor cell apoptosis. Moreover, 3p-GPC-3 siRNA was able to enhance the activation of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells while reducing the proportion of regulatory T cells (Tregs) in the TME. Most intriguingly, a blocking anti-PD-1 antibody improved the anti-tumor effect of 3p-GPC-3 siRNA, predominantly by activating the immune response, reversing immune exhaustion, and improving immune memory. Our study suggests that the combination of 3p-GPC-3 siRNA administration and PD-1 blockade may represent a promising therapeutic strategy for HCC.


Asunto(s)
Carcinoma Hepatocelular , Glipicanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Linfocitos T CD8-positivos , Glipicanos/genética , Glipicanos/uso terapéutico , Memoria Inmunológica/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéutico , Microambiente Tumoral , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico
8.
Front Immunol ; 13: 1046755, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36569893

RESUMEN

Immune checkpoint inhibitors (ICIs) have shown promising therapeutic effects in the treatment of advanced solid cancers, but their overall response rate is still very low for certain tumor subtypes, limiting their clinical scope. Moreover, the high incidence of drug resistance (including primary and acquired) and adverse effects pose significant challenges to the utilization of these therapies in the clinic. ICIs enhance T cell activation and reverse T cell exhaustion, which is a complex and multifactorial process suggesting that the regulatory mechanisms of ICI therapy are highly heterogeneous. Recently, metabolic reprogramming has emerged as a novel means of reversing T-cell exhaustion in the tumor microenvironment; there is increasing evidence that T cell metabolic disruption limits the therapeutic effect of ICIs. This review focuses on the crosstalk between T-cell metabolic reprogramming and ICI therapeutic efficacy, and summarizes recent strategies to improve drug tolerance and enhance anti-tumor effects by targeting T-cell metabolism alongside ICI therapy. The identification of potential targets for altering T-cell metabolism can significantly contribute to the development of methods to predict therapeutic responsiveness in patients receiving ICI therapy, which are currently unknown but would be of great clinical significance.


Asunto(s)
Neoplasias , Linfocitos T , Humanos , Linfocitos T/metabolismo , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias/terapia , Radioinmunoterapia , Microambiente Tumoral
9.
Chem Biol Interact ; 368: 110251, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36343683

RESUMEN

Edaravone (EDA), a strong novel free radical scavenger, have been demonstrated to exert neurovascular protective effects clinically. Furthermore, EDA can suppress the lung injury, pulmonary fibrosis and skin fibrosis, while the precise effects and mechanisms of EDA on liver injury and fibrosis remain unclear. The effects of EDA on the Thioacetamide (TAA)-induced liver fibrosis were evaluated by sirius red staining, α-SMA immunohistochemistry. The percentages of immune cell subsets were analyzed by flow cytometry. Immunofluorescence assay was performed to identify the fibrotic properties of hepatic stellate cells (HSCs). Western blot and qPCR were used to detect the levels of liver fibrosis-related molecules and IL-1ß. EDA displayed a hepatic protective role in TAA-induced chronic liver fibrosis via inhibiting monocyte/macrophages recruitment and IL-1ß production of macrophages. Mechanically, EDA inhibited of NF-κB signal pathway and reactive oxygen species (ROS) production in macrophages. Moreover, EDA treatment indirectly suppressed the activation of HSCs by decreasing the IL-1ß secretion of macrophages. Together, EDA protects against TAA-induced liver fibrosis via decreasing the IL-1ß production of macrophages, thereby providing a feasible solution for clinical treatment of liver fibrosis.


Asunto(s)
Células Estrelladas Hepáticas , Cirrosis Hepática , Humanos , Edaravona/efectos adversos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/prevención & control , Células Estrelladas Hepáticas/metabolismo , Tioacetamida/toxicidad , Fibrosis , Macrófagos/metabolismo , Hígado
10.
Biochem Pharmacol ; 206: 115334, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36328133

RESUMEN

Monocyte chemotactic protein-1 (MCP-1) is known to be able to facilitate vascular endothelial growth factor (VEGF) gene expression, hence promoting vascular hyperpermeability and neovascularization. We show here that a microRNA molecule, miR-374b-5p can target the 3'-untranslated region of the VEGF mRNA, thus preventing VEGF production. Additionally, MCP-1 promotes the acetylation of transcription factor stat3 at Lys685, which facilitates the formation of an ac-stat3-DNA methyltransferase-histone methyltransferase complex (ac-stat3/DNMT1/EZH2) that binds to the promoter of the miR-374b-5p gene. This results in diminished miR-374b-5p expression and enhanced VEGF production. Moreover, treatment of appropriate animal models either with a miR-374b-5p mimicry or with inhibitors of either stat3 acetylation, DNMT1, or EZH2, leads to marked inhibition of MCP-1-promoted neovascularization and tumor growth. These findings indicate that MCP-1 facilitated inhibition of miR-374b-5p gene expression leads to the removal of a block of VEGF mRNA translation by miR-374b-5p. This mechanism could be of importance in the modulation of inflammatory conditions.


Asunto(s)
MicroARNs , Factor A de Crecimiento Endotelial Vascular , Animales , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Biosíntesis de Proteínas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Regiones no Traducidas 3' , Neovascularización Patológica/genética
11.
Cell Mol Immunol ; 19(12): 1347-1360, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36369367

RESUMEN

Chronic hepatitis B (CHB) infection remains a serious public health problem worldwide; however, the relationship between cholesterol levels and CHB remains unclear. We isolated peripheral blood mononuclear cells from healthy blood donors and CHB patients to analyze free cholesterol levels, lipid raft formation, and cholesterol metabolism-related pathways. Hepatitis B virus (HBV)-carrier mice were generated and used to confirm changes in cholesterol metabolism and cell-surface lipid raft formation in dendritic cells (DCs) in the context of CHB. Additionally, HBV-carrier mice were immunized with a recombinant HBV vaccine (rHBVvac) combined with lipophilic statins and evaluated for vaccine efficacy against HBV. Serum samples were analyzed for HBsAg, anti-HBs, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg. CHB reduced free cholesterol levels and suppressed lipid raft formation on DCs in patients with CHB and HBV-carrier mice, whereas administration of lipophilic statins promoted free cholesterol accumulation and restored lipid rafts on DCs accompanied by an enhanced antigen-presentation ability in vitro and in vivo. Cholesterol accumulation on DCs improved the rHBVvac-mediated elimination of serum HBV DNA and intrahepatic HBV DNA, HBV RNA, and HBcAg and promoted the rHBVvac-mediated generation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells, induction of the development of memory responses against HBV reinfection, and seroconversion from HBsAg to anti-HBs. The results demonstrated the important role of cholesterol levels in DC dysfunction during CHB, suggesting that strategies to increase cholesterol accumulation on DCs might enhance therapeutic vaccine efficacy against HBV and support development toward clinical CHB treatment.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Vacunas , Ratones , Animales , Antígenos de Superficie de la Hepatitis B , Antígenos del Núcleo de la Hepatitis B/uso terapéutico , ADN Viral , Leucocitos Mononucleares , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Virus de la Hepatitis B , Anticuerpos contra la Hepatitis B , Células Dendríticas , Colesterol/uso terapéutico , ARN
12.
Emerg Microbes Infect ; 11(1): 2529-2543, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36153658

RESUMEN

Autophagy, a cellular surveillance mechanism, plays an important role in combating invading pathogens. However, viruses have evolved various strategies to disrupt autophagy and even hijack it for replication and release. Here, we demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) non-structural protein 1(nsp1) induces autophagy but inhibits autophagic activity. MERS-CoV nsp1 expression increased ROS and reduced ATP levels in cells, which activated AMPK and inhibited the mTOR signalling pathway, resulting in autophagy induction. Meanwhile, as an endonuclease, MERS-CoV nsp1 downregulated the mRNA of lysosome-related genes that were enriched in nsp1-located granules, which diminished lysosomal biogenesis and acidification, and inhibited autophagic flux. Importantly, MERS-CoV nsp1-induced autophagy can lead to cell death in vitro and in vivo. These findings clarify the mechanism by which MERS-CoV nsp1-mediated autophagy regulation, providing new insights for the prevention and treatment of the coronavirus.


Asunto(s)
Coronavirus del Síndrome Respiratorio de Oriente Medio , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Especies Reactivas de Oxígeno/metabolismo , ARN Mensajero/metabolismo , Lisosomas/metabolismo , Autofagia , Endonucleasas/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Adenosina Trifosfato/metabolismo
13.
Cancer Lett ; 547: 215880, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-35981569

RESUMEN

Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, it is difficult to alleviate this disease process using single-agent chemotherapy. Using combination therapies for advanced HCC has become a major trend. Given that STAT3 overexpression is involved in chemotherapy resistance and the immune escape of HCC cells, it has become a potential therapeutic target for HCC in recent years. GEO database analysis showed that STAT3 levels in tumor tissues from non-responders were significantly higher than those in responders to sorafenib. Our studies demonstrated that STAT3 knockdown promoted sorafenib-induced ER stress-induced apoptosis. Importantly, the DNA released by dead HCC cells stimulated the cGAS-STING signaling pathway in CD103+ DCs and promoted type I interferon production, thus, enhancing the anti-tumor function of CD8+ T and NK cells. In conclusion, our results revealed that the combination strategy of sorafenib and STAT3 knockdown might be a potential treatment strategy for HCC, directly and efficiently disturbing the tumor features of HCC cells while improving the tumor microenvironment via the cGAS-STING-Type I IFNs axis of DCs, inducing anti-HCC immune responses.


Asunto(s)
Carcinoma Hepatocelular , Estrés del Retículo Endoplásmico , Neoplasias Hepáticas , Apoptosis , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/uso terapéutico , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Sorafenib/farmacología , Sorafenib/uso terapéutico , Microambiente Tumoral
14.
Mol Oncol ; 16(15): 2861-2880, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35665592

RESUMEN

In hepatocellular carcinoma (HCC), the signal transducer and activator of transcription 3 (STAT3) is present in an overactive state that is closely related to tumour development and immune escape. STAT3 inhibition reshapes the tumour immune microenvironment, but the underlying mechanisms have not been fully clarified. We found that STAT3 inhibition could induce immunogenic cell death (ICD) of HCC cells via translocation of the "eat me" molecule calreticulin to the cell surface and a significant reduction in the expression of the "don't eat me" molecule leucocyte surface antigen CD47. STAT3 inhibition promoted dendritic cell (DC) activation and enhanced the recognition and phagocytosis of HCC cells by macrophages. Furthermore, STAT3 inhibition prevented the expression of key glycolytic enzymes, facilitating the induction of ICD in HCC. Interestingly, STAT3 directly regulated the transcription of CD47 and solute carrier family 2 member 1 (SLC2A1; also known as GLUT1). In subcutaneous and orthotopic transplantation mouse tumour models, the STAT3 inhibitor napabucasin prevented tumour growth and induced the expression of calreticulin and the protein disulfide isomerase family A member 3 (PDIA3; also known as ERp57) but suppressed that of CD47 and GLUT1. Meanwhile, the amount of tumour-infiltrated DCs and macrophages increased, along with the expression of costimulatory molecules. More CD4+ and CD8+ T cells accumulated in tumour tissues, and CD8+ T cells had lower expression of checkpoint molecules such as lymphocyte activation gene 3 protein (LAG-3) and programmed cell death protein 1 (PD-1). Significantly, the antitumour immune memory response was induced by treatment targeting STAT3. These findings provide a new mechanism for targeting STAT3-induced ICD in HCC, and confirms STAT3 as a potential target for the treatment of HCC via reshaping the tumour immune microenvironment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Antígeno CD47/metabolismo , Linfocitos T CD8-positivos/metabolismo , Calreticulina/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Transportador de Glucosa de Tipo 1/metabolismo , Glucólisis , Muerte Celular Inmunogénica , Neoplasias Hepáticas/patología , Ratones , Factor de Transcripción STAT3/metabolismo , Microambiente Tumoral
15.
World J Gastroenterol ; 28(9): 881-896, 2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35317051

RESUMEN

Chronic hepatitis B virus (HBV) infection is an international health problem with extremely high mortality and morbidity rates. Although current clinical chronic hepatitis B (CHB) treatment strategies can partly inhibit and eliminate HBV, viral breakthrough may result due to non-adherence to treatment, the emergence of viral resistance, and a long treatment cycle. Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems. Therefore, understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control. This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Virus de la Hepatitis B , Humanos
16.
Phys Chem Chem Phys ; 24(14): 8303-8310, 2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35319033

RESUMEN

Benefiting from the easily adjustable optical properties of perovskite, CsPbBr3 nanocrystals (NCs) are considered to show their advantages in the field of display. Here, we report that a selective laser irradiation is used to induce CsPbBr3 nanostructural reshaping and then yielding a morphological change. Under 360 or 405 nm laser irradiation, a hierarchical crystal growth process occurs for the fabricated CsPbBr3 nanoplatelets (NPLs), which are first arranged in a side-by-side manner and reshaped into nanorods (NRs), and then NRs are arranged in the face-to-face manner to reshape into NCs. The entire process is monitored optically and microscopically, which showed that crystal growth relies on seeking a dynamic balance between heat dissipation and accumulation under laser irradiation. The heat on NPLs generated by laser irradiation dissipated with a low dissipation rate and thus led to temperature rising and lattice breaking, which turned out to be the driving force for the crystal growth in CsPbBr3 NPLs. This feasible laser irradiation-assisted method provides for crystal growth a reliable and scalable route toward the preparation of perovskite functional materials.

17.
Oncoimmunology ; 11(1): 2032918, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35127254

RESUMEN

Macrophages of the M2 phenotype in malignant tumors significantly aid tumor progression and metastasis, as opposed to the M1 phenotype that exhibits anti-cancer characteristics. Raising the ratio of M1/M2 is thus a promising strategy to ameliorate the tumor immunomicroenvironment toward cancer inhibition. We report here that tumor necrosis factor superfamily-15 (TNFSF15), a cytokine with anti-angiogenic activities, is able to facilitate the differentiation and polarization of macrophages toward M1 phenotype. We found that tumors formed in mice by Lewis lung carcinoma (LLC) cells artificially overexpressing TNFSF15 exhibited retarded growth. The tumors displayed a greater percentage of M1 macrophages than those formed by mock-transfected LLC cells. Treatment of mouse macrophage RAW264.7 cells with recombinant TNFSF15 led to augmentation of the phagocytic and pro-apoptotic capacity of the macrophages against cancer cells. Mechanistically, TNFSF15 activated STAT1/3 in bone marrow cells and MAPK, Akt and STAT1/3 in naive macrophages. Additionally, TNFSF15 activated STAT1/3 but inactivated STAT6 in M2 macrophages. Modulations of these signals gave rise to a reposition of macrophage phenotypes toward M1. The ability of TNFSF15 to promote macrophage differentiation and polarization toward M1 suggests that this unique cytokine may have a utility in the reconstruction of the immunomicroenvironment in favor of tumor suppression.


Asunto(s)
Carcinoma Pulmonar de Lewis , Macrófagos , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Animales , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Diferenciación Celular , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Fenotipo , Células RAW 264.7 , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa
18.
Virulence ; 13(1): 355-369, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35129074

RESUMEN

MERS-CoV infection can damage the cellular metabolic processes, but the underlying mechanisms are largely unknown. Through screening, we found non-structural protein 1 (nsp1) of MERS-CoV could inhibit cell viability, cell cycle, and cell migration through its endonuclease activity. Transcriptome sequencing revealed that MERS-CoV nsp1 specifically downregulated the mRNAs of ribosomal protein genes, oxidative phosphorylation protein genes, and antigen presentation genes, but upregulated the mRNAs of transcriptional regulatory genes. Further analysis shown nsp1 existed in a novel ribonucleosome complex formed via liquid-liquid phase separation, which did not co-localize with mitochondria, lysosomes, P-bodies, or stress granules. Interestingly, the nsp1-located granules specifically contained mRNAs of ribosomal protein genes and oxidative phosphorylation genes, which may explain why MERS-CoV nsp1 selectively degraded these mRNAs in cells. Finally, MERS-CoV nsp1 transgenic mice showed significant loss of body weight and an increased sensitivity to poly(I:C)-induced inflammatory death. These findings demonstrate a new mechanism by which MERS-CoV impairs cell viability, which serves as a potential novel target for preventing MERS-CoV infection-induced pathological damage.Abbreviations: (Middle East respiratory syndrome coronavirus (MERS-CoV), Actinomycin D (Act D), liquid-liquid phase separation (LLPS), stress granules (SGs), Mass spectrometry (IP-MS), RNA Binding Protein Immunoprecipitation (RIP)).


Asunto(s)
Infecciones por Coronavirus , Coronavirus del Síndrome Respiratorio de Oriente Medio , Proteínas Ribosómicas , Proteínas no Estructurales Virales , Animales , Regulación de la Expresión Génica , Ratones , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , ARN Mensajero/genética , Proteínas Ribosómicas/genética
19.
Int J Biol Sci ; 18(1): 154-165, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34975324

RESUMEN

Chronic Hepatitis B virus (CHB) infection is a global public health problem. Oligodeoxynucleotides (ODNs) containing class C unmethylated cytosine-guanine dinucleotide (CpG-C) motifs may provide potential adjuvants for the immunotherapeutic strategy against CHB, since CpG-C ODNs stimulate both B cell and dendritic cell (DC) activation. However, the efficacy of CpG-C ODN as an anti-HBV vaccine adjuvant remains unclear. In this study, we demonstrated that CpG M362 (CpG-C ODN) as an adjuvant in anti-HBV vaccine (cHBV-vaccine) successfully and safely eliminated the virus in HBV-carrier mice. The cHBV-vaccine enhanced DC maturation both in vivo and in vitro, overcame immune tolerance, and recovered exhausted T cells in HBV-carrier mice. Furthermore, the cHBV-vaccine elicited robust hepatic HBV-specific CD8+ and CD4+ T cell responses, with increased cellular proliferation and IFN-γ secretion. Additionally, the cHBV-vaccine invoked a long-lasting follicular CXCR5+ CD8+ T cell response following HBV re-challenge. Taken together, CpG M362 in combination with rHBVvac cleared persistent HBV and achieved long-term virological control, making it a promising candidate for treating CHB.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Fosfatos de Dinucleósidos/inmunología , Vacunas contra Hepatitis B/farmacología , Hepatitis B Crónica/inmunología , Oligodesoxirribonucleótidos/inmunología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL
20.
J Phys Chem Lett ; 13(4): 962-968, 2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35060729

RESUMEN

In this Letter, erbium (Er3+) and ytterbium (Yb3+) codoped perovskite Cs2Ag0.6Na0.4In0.9Bi0.1Cl6 microcrystal (MC) is synthesized and demonstrated systematically to the most prospective optical temperature sensing materials. A dual-mode thermometry based on fluorescence intensity ratio and fluorescence lifetime provides a self-reference and highly sensitive temperature measurement under dual wavelength excitation at a temperature from 300 to 470 K. Combined with the white-light emission derived from self-trapped excitons (STEs), the characteristic emission peak of Er3+ ions can be observed under 405 nm laser excitation. The fluorescence intensity ratio (FIR) between perovskite and Er3+ is used as temperature-dependent probe signal, of which maximum value for relative and absolute sensitivities reaches to 1.40% K-1 and 8.20 × 10-2 K-1. Moreover, Er3+ luminescence becomes stronger with the feeding Yb3+ increasing under 980 nm laser excitation. The energy transfer of Er3+ and Yb3+ is revealed by power-dependent photoluminescence (PL) spectroscopy, and the involved upconversion mechanism pertains to the two-photon excitation process. The results reveal that the Er3+/Yb3+ codoped lead-free double perovskite MC is a good candidate for a thermometric material for the novel dual-mode design.

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