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Interleukin-1α is mainly expressed on the cell membrane, but can also be secreted during inflammation. The roles of secreted and membrane IL-1α in acute liver inflammation are still not known. Here, we examined the functions of secreted and membrane IL-1α in a mouse model of carbon tetrachloride-induced acute liver injury. We show that secreted IL-1α aggravates liver damage and membrane IL-1α slightly protects mice from liver injury. Further studies showed that secreted IL-1α promotes T-cell activation. It also increased the expansion of CD11b+Gr1+ myeloid cells, which may serve as a negative regulator of acute liver inflammation. Moreover, secreted IL-1α induced IL-6 production from hepatocytes. IL-6 neutralization reduced the proliferation of CD11b+Gr1+ myeloid cells in vivo. CCL2 and CXCL5 expression was increased by secreted IL-1α in vitro and in vivo. Antagonists of the chemokine receptors for CCL2 and CXCL5 significantly reduced the migration of CD11b+Gr1+ myeloid cells. These results demonstrate that secreted and membrane IL-1α play different roles in acute liver injury. Secreted IL-1α could promote T-cell activation and the recruitment and expansion of CD11b+Gr1+ myeloid cells through induction of CCL2, CXCL5, and IL-6. The controlled release of IL-1α could be a critical regulator during acute liver inflammation. [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to systematically review the evidence on cancer risk of the MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model (OR = 1.11, 95% CI: 1.04–1.19), homozygote model (OR = 1.22, 95% CI: 1.05–1.41), heterozygote model (OR = 1.21, 95% CI: 1.07–1.36), and dominant model (OR = 1.21, 95% CI: 1.08–1.35). However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) contribute to antigen capture, uptake, presentation and activation of immune responses. We recently developed a new and lymph node (LN) targeting adjuvant (D-CpG) by chemical conjugation type B CpG DNA with FDA-approved dextran polymer for lymph node imaging. To elucidate the possible antitumor mechanisms of this adjuvant, prophylaxis and therapeutic models of melanoma were used in this study. Our results showed that D-CpG was an efficient adjuvant of protein-based tumor vaccine in both prophylaxis and therapeutic models. It enhanced the tumor-specific Th1 and CTL responses. It also facilitated the tumor infiltration of the T cells and promoted IFNγ and TNFα production of both CD4+ and CD8+ T cells. In therapeutic model, D-CpG included tumor vaccine decreased the percentage of CD11b+Gr1low+ MDSCs in spleen and inhibited their infiltration in tumor microenvironments. Administration of the D-CpG included vaccine significantly inhibited lung metastasis of the tumor through similar mechanisms. In conclusion, D-CpG used as tumor vaccine adjuvant can enhance both Th1 and CTL responses and inhibit CD11b+Gr1low MDSCs, which may have general applicability to the development of vaccines against tumors. [ABSTRACT FROM AUTHOR]

Objective: Radiotherapy is an effective treatment for head and neck cancer; however, irradiated normal tissues are inevitably damaged, resulting in skin radioactive fibrosis. Dicliptera chinensis polysaccharide (DCP), the primary active compound extracted from the natural medicinal Dicliptera chinensis, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we investigated the protective effects of DCP against radioactive fibrosis in rat dermal fibroblasts (RDF) and explored the underlying mechanisms involved., Design: RDFs were treated with DCP, and the CCK8 assay was used to determine cellular activity. The rates of apoptosis and cell cycle progression were detected using flow cytometry. mRNA expression levels were quantified using real-time polymerase chain reaction. Protein levels were analysed through Western blotting and immunofluorescence staining RESULTS: DCP reduced radiation-induced apoptosis, and the cell cycle G2/M arrest was alleviated. Furthermore, DCP decreased the expression of key fibrosis-related markers, including α-SMA, TGF-β1, Smad3, and CTGF., Conclusion: DCP exhibits a protective effect against radiation-induced fibrosis., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection., Importance: As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection., Competing Interests: The authors declare no conflict of interest.

Purpose: To investigate whether Dicliptera chinensis polysaccharide (DCP) can alleviate radiation-induced fibrosis of masseter and head and neck skin., Methods: SD rats were divided into the control, the irradiation (IR), the IR + low dose DCP (200 mg/kg), and the IR + high dose DCP (400 mg/kg) groups. The head and neck of rats in the last 3 groups received a single dose of 18 Gy X-ray. At 1st, 2nd, 4th week (w) after radiation, haematoxylin and eosin staining were performed on masseter and skin to observe the histopathological changes; immunohistochemistry staining was performed to observe the pathological changes of the skin; Masson staining was performed on masseter and skin to observe the collagen deposition; western blot analysis was used on masseter to calculate the relative transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF) expressions; ELISA was used to detect the contents of TGF-β1 and CTGF in skin and the contents of type I and type III collagens in masseter and skin., Results: In terms of skin, compared to the IR group, the IR + high-dose DCP group exhibited relatively smaller changes in skin structure, lower levels of TGF-β1 and CTGF; thinner skin thickness was observed at the 4th w after radiation; and the positive rates of collagen fibre and the optical densities of type I and type III collagens were lower at the 2nd and 4th w. For the masseter, compared to the IR group, the morphological changes were improved and the expression levels of TGF-β1 and CTGF proteins decreased in the 2 DCP dose groups at 2nd and 4th w., Conclusion: DCP can reduce the formation and accumulation of type I and type III collagens after IR and ameliorate radiation-induced fibrosis of masseter and skin by down-regulating the expressions of TGF-β1 and CTGF., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The salivary gland (SGS) is a kind of organ vulnerable to ionizing radiation. Radiotherapy is an important treatment for head and neck tumors, but in the process of radiotherapy, tumor cells will be injured by radiation to a certain extent. Infrared-induced DNA double-strand break (IR-DSBs) is one of the most serious DNA damage. DNA repair proteins such as Nymegan rupture syndrome protein 1 (NBS1) play a key role in the identification and repair of DNA damage. but the interaction between SSB1 and NBS1 has not been elucidated. In this study, we irradiated rat submandibular gland (SMG) cells, which were either infected with a rAdE5-SSB1-1p2-shRNA recombinant adenovirus to silence SSB or a control virus, to explore the effect of IR on the expression NBS1 in the absence of SSB. Our results showed that the SSB1 mRNA transcripts and protein expression of SSB1 and NBS1 initially increased and decreased later with increased doses. The relative expression reached the highest levels when the SMG cells were irradiated with 2Gy of IR. Silencing the SSB1 gene suppressed the expression of both SSB1 and NBS1 regardless of irradiation. The expression of NBS1 decreased when the SSB1 gene was silenced. We concluded that IR affected the expression of both SSB1 and NBS1 and there is a synergistic effect on IR-induced NBS1 suppression and DSBs repair in SMG cells. These observations shed light on further investigation and elucidation of IR-caused DNA repair mechanisms.

Interleukin-24 (IL-24) is a promising agent for cancer immunotherapy that induces apoptosis of tumor cells and enhances T cell activation and function. In order to improve the antitumor activity induced by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV expressing IL-24 using reverse genetics. Irradiated tumor cells infected with LX/IL-24 showed stable IL-24 expression. The cytotoxicity assay showed that LX/IL-24-infected murine melanoma cells significantly enhanced the antitumor immune response in vitro . Then, the antitumor effects of virus-infected tumor cells were examined in the murine tumor models. LX/IL-24-infected tumor cells exhibited strong antitumor effects both in prophylaxis and therapeutic models. LX/IL-24-infected tumor cells increased infiltration of CD4 + T cells and CD8 + T cells in tumor sites, and the antitumor activity of the tumor vaccine modified with LX/IL-24 was dependent on CD8 + T cells. Taken together, our data well illustrates that LX/IL-24-modified tumor cells are a promising agent for cancer immunotherapy.

Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) contribute to antigen capture, uptake, presentation and activation of immune responses. We recently developed a new and lymph node (LN) targeting adjuvant (D-CpG) by chemical conjugation type B CpG DNA with FDA-approved dextran polymer for lymph node imaging. To elucidate the possible antitumor mechanisms of this adjuvant, prophylaxis and therapeutic models of melanoma were used in this study. Our results showed that D-CpG was an efficient adjuvant of protein-based tumor vaccine in both prophylaxis and therapeutic models. It enhanced the tumor-specific Th1 and CTL responses. It also facilitated the tumor infiltration of the T cells and promoted IFNγ and TNFα production of both CD4 + and CD8 + T cells. In therapeutic model, D-CpG included tumor vaccine decreased the percentage of CD11b + Gr1 low+ MDSCs in spleen and inhibited their infiltration in tumor microenvironments. Administration of the D-CpG included vaccine significantly inhibited lung metastasis of the tumor through similar mechanisms. In conclusion, D-CpG used as tumor vaccine adjuvant can enhance both Th1 and CTL responses and inhibit CD11b + Gr1 low MDSCs, which may have general applicability to the development of vaccines against tumors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Stimulation of tumor-specific responses in both CD4 + and CD8 + T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4 + and CD8 + T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. CD4 + or CD8 + T-cell depletion resulted in the loss of antitumor activity of the Salmonella tumor vaccine, suggesting that the efficacy of the vaccine was dependent on both CD4 + and CD8 + T cells. Lung metastasis of the tumor was also inhibited by vaccine treatment. Similarly, the percentages of tumor-specific Th1 cytokine production by CD4 + and CD8 + T cells in the spleen, tumor, and bronchoalveolar lavage were increased after vaccine treatment. Tumor-specific proliferation of CD4 + and CD8 + T cells was also promoted by the vaccine. Tetramer staining and cytotoxicity assay showed enhanced tumor-specific CD8 + T-cell response after vaccine treatment. Therefore, the Salmonella tumor vaccine could activate both tumor-specific CD4 + and CD8 + T-cell responses. This vaccine strategy may be widely applicable to the development of oral or nasal vaccines against tumors. Cancer Immunol Res; 5(6); 503-14. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Interleukin-1α is mainly expressed on the cell membrane, but can also be secreted during inflammation. The roles of secreted and membrane IL-1α in acute liver inflammation are still not known. Here, we examined the functions of secreted and membrane IL-1α in a mouse model of carbon tetrachloride-induced acute liver injury. We show that secreted IL-1α aggravates liver damage and membrane IL-1α slightly protects mice from liver injury. Further studies showed that secreted IL-1α promotes T-cell activation. It also increased the expansion of CD11b(+) Gr1(+) myeloid cells, which may serve as a negative regulator of acute liver inflammation. Moreover, secreted IL-1α induced IL-6 production from hepatocytes. IL-6 neutralization reduced the proliferation of CD11b(+) Gr1(+) myeloid cells in vivo. CCL2 and CXCL5 expression was increased by secreted IL-1α in vitro and in vivo. Antagonists of the chemokine receptors for CCL2 and CXCL5 significantly reduced the migration of CD11b(+) Gr1(+) myeloid cells. These results demonstrate that secreted and membrane IL-1α play different roles in acute liver injury. Secreted IL-1α could promote T-cell activation and the recruitment and expansion of CD11b(+) Gr1(+) myeloid cells through induction of CCL2, CXCL5, and IL-6. The controlled release of IL-1α could be a critical regulator during acute liver inflammation., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel biodegradable thiazolidine-2-thione functional chain transfer agent was synthesized and employed as a reversible additional fragmentation chain transfer agent to prepare well-defined semitelechelic poly-N-(2-hydroxypropyl) methacrylamides (polyHPMAs) with predetermined molecular weights and narrow polydispersities. The protein reactive group, thiazolidine-2-thione, was located at the polymer chain ends fixed by biodegradable disulfide bonds. The functional polyHPMA chains were subsequently conjugated to protein (lysozyme) by exploiting reactions between the thiazolidine-2-thione functionality and amine residues on the protein surface to form covalent amide linkages. The in vitro bioactivities of the lysozyme-polyHPMA conjugates were assessed by using Micrococcus lysodeikticus cells as substrates. The lysozyme bioactivity was significantly reduced following the conjugation procedure. However, cleavage of the polymer chains from the bioconjugates (under reducing conditions) yielded free protein and a remarkable recovery of bioactivity. In vivo tests were performed by subcutaneous injection into mice and clearly demonstrated decreased proteolytic degradation for the protein-polymer conjugate when compared with native protein, indicating effective protein protection through a conjugation strategy. This bioreversible approach to conjugation allows for a balance to be made between protein protection and effective bioactivity maintenance., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recombinant human myxovirus resistance protein A (MxA) was successfully expressed by an Escherichia coli expression system. After immunization and cell fusion, a mouse hybridoma (3C2) producing MAbs to MxA was established. Hybridoma 3C2 was further characterized using indirect ELISA, Western blot analysis, immunofluorescent staining, and immunoprecipitation. The ELISA results showed that the titer of 3C2 was between 1:6400 and 1:12800 in ascitic fluids. The isotype of the monoclonal antibody was tested to be IgG1kappa. 3C2 can also specifically recognize human MxA protein in various formats by Western blot analysis, immunofluorescent staining, and immunoprecipitation assay. We further demonstrated that 3C2 could be used to detected MxA expression induce by type I interferon in A549 cell line and human peripheral blood mononuclear cells by Western blot in a dose-dependent manner.

Objective: We determined the distribution of serogroups and virulence factors among Escherichia coli isolates from pigs with diarrhea and/or edema disease from 10 provinces in China between 1998 and 2007., Methods: Three hundred E. coli isolates were serogrouped with O-antisera and detected for genes of enterotoxins, shiga-toxin-two-variant (Stx2e), intimin, K88, K99, 987P, F18 and F41 fimbrial antigens by PCR., Results: Among 300 isolates, 233 were determined to be placed in serogroups, 50 were unable to be serogrouped, and the rest 17 auto-agglutinated. These isolates distributed in 45 serogroups and 57.1% (133/233) belonged to 5 O serogroups: O149, O107, O139, O93 and O91. Several uncommon O serogroups were discovered. PCR analysis confirmed the genes of est I (STa), est II (STb), elt (LT), stx2e (Stx2e) and eaeA (Intimin) within the isolates. There were six pathotypes of porcine E. coli by their pathogenic factors, namely enterotoxigenic E. coli (ETEC), shiga toxin-producing E. coli (STEC), attaching-effacing E. coli (AEEC), ETEC/ STEC, AEEC/ETEC and AEEC/ETEC/STEC. The correlation between pathotypes and serogroups showed that the combinations of O149/K88/estII, O149/K88/est II+elt, O107/F18/est II, 093/est II and O98/est II were common types in ETEC strains, O139/ F18/stx2e for STEC strains, eaeA gene for AEEC strains, O107/F18/estI+stx2e, O107/F18/estII + stx2e and O116/F18/est I +elt+stx2e for ETEC/STEC strains, 091/est I/eaeA and O107/est I /eaeA for AEEC/ETEC/STEC strains"., Conclusion: ETEC was commonly associated with swine colibacillosis, whereas the kinds of enteric E. coli pathogens become more complex in China.

We constructed avian pathogenic Escherichia coli (APEC) specific DNA microarray to analyze the transcriptomes of APEC highly pathogenic strain E058 and low pathogenic strain E526 (both belonging to O2 serotype). For cultures in Luria-Bertani (LB) broth medium, 16 distinctly expressed genes were observed in strain E526, and all of them were down-regulated. For cultures in the serum of chickens, 15 distinctly expressed genes were screened in strain E526, and all of them were also down-regulated. The results suggest that DNA microarray could be used to screen distinctly expressed genes among virulence- and potential virulence-associated genes of APEC. The expression of 11 common virulence- or potential virulence-associated genes were down-regulated for strain E526 compared to those of strain E058 cultured both in LB broth and chicken serum. Meanwhile, 4 potential virulence-associated genes, aes-3, aes-10, aes-13 and aes-15 were down-regulated for strain E526 but not for strain E058, when they grew in the chicken serum. Besides known virulence factors, we observed 10 new potential virulence-related genes including aes-1, aes-2, aes-3, aes-4, aes-6, aes-8, aes-10, aes-13, aes-15 and aes-31.