Publications by authors named "Panpan Yi"

16 Publications

  • Page 1 of 1

IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice.

J Neuroinflammation 2020 Aug 25;17(1):249. Epub 2020 Aug 25.

Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.

Background: The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays, a role in ZIKV infection is unknown.

Methods: The cellular source of IL-22 was identified in IFNAR mice and wild-type (WT) neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old WT and IL-22 mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8 T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, glial cells were cultured in vitro and infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression, and viral loads.

Results: We found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to exhibit weight loss, staggered steps, bilateral hind limb paralysis, and weakness at 10 days post-infection (dpi) and ultimately succumbed to infection at 16-19 dpi. IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly improved clinical signs of neurological disease and mortality. ZIKV infection also induced the activation of microglia and astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a negligible effect on glial cells in vitro, IL-22 mice mounted more vigorous ZIKV-specific CD8 T cell responses, which led to a more effective control of ZIKV in the brain.

Conclusions: Our data revealed a pathogenic role of IL-22 in ZIKV encephalitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-020-01928-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448338PMC
August 2020

Retinoic Acid Modulates Hyperactive T Cell Responses and Protects Vitamin A-Deficient Mice against Persistent Lymphocytic Choriomeningitis Virus Infection.

J Immunol 2020 06 13;204(11):2984-2994. Epub 2020 Apr 13.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;

Vitamin A deficiency (VAD) is a major public health problem and is associated with increased host susceptibility to infection; however, how VAD influences viral infection remains unclear. Using a persistent lymphocytic choriomeningitis virus infection model, we showed in this study that although VAD did not alter innate type I IFN production, infected VAD mice had hyperactive, virus-specific T cell responses at both the acute and contraction stages, showing significantly decreased PD-1 but increased cytokine (IFN-γ, TNF-α, and IL-2) expression by T cells. Compared with control mice, VAD mice displayed excessive inflammation and more severe liver pathology, with increased death during persistent infection. Of note, supplements of all- retinoic acid (RA), one of the important metabolites of vitamin A, downregulated hyperactive T cell responses and rescued the persistently infected VAD mice. By using adoptive transfer of splenocytes, we found that the environmental vitamin A or its metabolites acted as rheostats modulating antiviral T cells. The analyses of T cell transcriptional factors and signaling pathways revealed the possible mechanisms of RA, as its supplements inhibited the abundance of NFATc1 (NFAT 1), a key regulator for T cell activation. Also, following CD3/CD28 cross-linking stimulation, RA negatively regulated the TCR-proximal signaling in T cells, via decreased phosphorylation of Zap70 and its downstream signals, including phosphorylated AKT, p38, ERK, and S6, respectively. Together, our data reveal VAD-mediated alterations in antiviral T cell responses and highlight the potential utility of RA for modulating excessive immune responses and tissue injury in infectious diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1901091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371257PMC
June 2020

Correlation of Long Noncoding RNA SEMA6A-AS1 Expression with Clinical Outcome in HBV-Related Hepatocellular Carcinoma.

Clin Ther 2020 03 15;42(3):439-447. Epub 2020 Feb 15.

Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Purpose: Hepatocellular carcinoma (HCC) is the seventh most commonly diagnosed cancer and the fourth-leading cause of cancer-related death worldwide. Chronic hepatitis B virus (HBV) is the leading cause of HCC in China. Emerging evidence suggests that long noncoding (lnc)-RNAs are deregulated and are involved in the development of HCC. Our previous study found that HBV X protein can promote HCC by altering lncRNA expression profiles. The purpose of this study was to investigate the expression of the lncRNA semaphorin 6A-antisense RNA 1 (SEMA6A-AS1) and its prognostic value in HBV-related HCC.

Methods: Samples of HCC tissues and adjacent nontumor tissues were collected from patients who were pathologically diagnosed with HBV-related HCC after hepatectomy. Eligible patients had not received preoperative radiotherapy, chemotherapy, or embolotherapy. Real-time quantitative reverse-transcription polymerase chain reaction was performed to evaluate the expression levels of SEMA6A-AS1 in all tissue specimens. The correlations between SEMA6A-AS1 expression and clinicopathologic characteristics were analyzed using the χ test and the Fisher exact test. Overall survival curves constructed by the Kaplan-Meier method and univariate analysis made by Cox proportional hazards modeling were used for determining the prognostic significance of SEMA6A-AS1.

Findings: Specimens were collected from 47 patients (45 men, 2 women; mean age, 48.4 [10.7] years). SEMA6A-AS1 expression was significantly downregulated in HBV-related HCC tissues compared with that in adjacent noncancerous hepatic tissues (P < 0.01). Low levels of SEMA6A-AS1 were correlated with high α-fetoprotein level (P = 0.002), high Edmondson-Steiner tumor grade (P = 0.047), high tumor node metastasis stage (P = 0.01), capsular invasion (P = 0.005), and poor clinical response (P = 0.002). Additionally, both Kaplan-Meier estimator and univariate Cox regression analysis revealed that low SEMA6A-AS1 expression was significantly associated with poor overall survival (P < 0.05).

Implications: The results show that low expression of SEMA6A-AS1 was associated with a poor prognosis in patients with HBV-related HCC. It is necessary to determine the function and mechanism of SEMA6A-AS1 in HCC in order to identify it as a prognostic biomarker and therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2020.01.012DOI Listing
March 2020

A novel lncRNA, TCONS_00006195, represses hepatocellular carcinoma progression by inhibiting enzymatic activity of ENO1.

Cell Death Dis 2018 12 5;9(12):1184. Epub 2018 Dec 5.

Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and has an unfavorable prognosis. The hepatitis B virus X (HBx) protein has been reported to be closely associated with hepatocarcinogenesis. Meanwhile, emerging evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the pathogenesis and progression of cancers. Our previous investigation has demonstrated that HBx could promote HCC by regulating the expression levels of various lncRNAs. In this study, we identified an lncRNA, lncRNA-TCONS_00006195 (termed lncRNA-6195), which was downregulated in HBV-related HCC tissues compared with its expression in adjacent noncancerous hepatic tissues. Clinical data showed that a low level of lncRNA-6195 was correlated with a high Edmondson-Steiner grade of the tumor and a poor prognosis in HCC patients. Furthermore, lncRNA-6195 acted as a tumor repressor in the development of hepatitis B-related HCC, inhibiting HCC cell proliferation in vitro and in vivo. Moreover, lncRNA-6195 could combine with α-enolase (ENO1) and repress its enzymatic activity, thus further inhibiting the energy metabolism in HCC cells. Our results suggest that lncRNA-6195 represses the growth of HCC by inhibiting the enzymatic activity of ENO1. These findings provide new insights into the mechanisms underlying the lncRNA involvement in hepatocarcinogenesis and can serve as a basis for the development of novel strategies to hinder HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-1231-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281672PMC
December 2018

Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling.

Cell Cycle 2018 22;17(19-20):2349-2359. Epub 2018 Oct 22.

d Department of Surgery , University of Pittsburgh , Pittsburgh , PA , USA.

Hepatocellular carcinoma (HCC), one of the most common type of cancers, is highly refractory to most systemic therapies. Understanding the genomic dysregulations, in particularly non-coding RNA (ncRNA) dysregulations, in HCC may provide novel strategies to HCC treatment. In our previous study, we demonstrated the key role of miR-200a-mediated HMGB1/RAGE signaling in HCC carcinogenesis. In the present study, we identified circular RNA (circRNA)-miRNA pair that might modulate the migration of HCC cell lines based on previously reported GEO database (GSE78520 and GSE43445) and investigated the function and molecular mechanism. circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC. Moreover, circRNA-101368 knockdown suppressed the migration and the protein levels of HMGB1, RAGE and NF-κB, while increased the E-Cadherin expression in HCC cell lines. As confirmed by luciferase reporter and RNA immunoprecipitation assays, circRNA-101368 directly bound to miR-200a to negatively regulate each other. The effect of circRNA-101368 knockdown on cell migration and HMGB1/RAGE signaling could be partially attenuated by miR-200a inhibition. In tissue samples, miR-200a was negatively correlated with circRNA-101368 and HMGB1, respectively, whereas circRNA-101368 and HMGB1 was positively correlated. Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2018.1526599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237437PMC
November 2019

IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis.

Cell Mol Immunol 2019 02 5;16(2):126-137. Epub 2018 Feb 5.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, 77555-1070, USA, TX.

Viral hepatitis is still a public health problem affecting several million people around the world. Neutrophils are polymorphonuclear cells that have a critical role in antibacterial infection. However, the role of neutrophils in viral infection is not fully understood. By using a mouse model of lymphocytic choriomeningitis virus infection-induced viral hepatitis, we observed increased neutrophil recruitment in the liver accompanied by enhanced CD8 T-cell responses. Liver neutrophils expressed high levels of immunomodulatory cytokines, such as C-X-C chemokine ligand 2, arginase-1, inducible nitric oxide synthase and interleukin (IL)-10, demonstrating immunosuppressive properties. Depletion of neutrophils in vivo by a neutralizing antibody resulted in the exacerbation of liver injury and the promotion of T-cell responses at the immune contraction stage. IL-33 significantly induced neutrophil recruitment in the liver and attenuated liver injury by limiting effector T-cell accumulation. Mechanistically, we found that IL-33 promoted the expression of arginase-1 in neutrophils through the type 2 innate lymphoid cell (ILC2)-derived IL-13. Additionally, IL-13 increased the inhibitory effect of neutrophils on CD8 T-cell proliferation in vitro, partially through arginase-1. Finally, we found that IL-13 induced arginase-1 expression, depending on signal transducer and activator of transcription factor 6 (STAT6) signaling. Therefore, IL-33 induced immunosuppressive neutrophils via an ILC2/IL-13/STAT6 axis. Collectively, our findings shed new light on the mechanisms associated with IL-33-triggered neutrophils in the liver and suggest potential targets for therapeutic investigation in viral hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/cmi.2017.147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355846PMC
February 2019

Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action.

Cell Rep 2017 Nov;21(6):1588-1599

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address:

Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise. In addition, prophylactic and therapeutic treatment of IFN-λ1 in a human trophoblast line, as well as in primary human amniotic epithelial cells, greatly reduced the ZIKV burden. Our data highlight IFN-λ1 as a potential therapeutic useful for women at risk for congenital Zika disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2017.10.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726784PMC
November 2017

High invasion potential of in the Americas predicted using ecological niche modeling combined with genetic data.

Ecol Evol 2017 07 30;7(13):4982-4990. Epub 2017 May 30.

National Field Station of Freshwater Ecosystem of Liangzi Lake College of Life Sciences Wuhan University Wuhan China.

Ecological niche modeling is an effective tool to characterize the spatial distribution of suitable areas for species, and it is especially useful for predicting the potential distribution of invasive species. The widespread submerged plant (hydrilla) has an obvious phylogeographical pattern: Four genetic lineages occupy distinct regions in native range, and only one lineage invades the Americas. Here, we aimed to evaluate climatic niche conservatism of hydrilla in North America at the intraspecific level and explore its invasion potential in the Americas by comparing climatic niches in a phylogenetic context. Niche shift was found in the invasion process of hydrilla in North America, which is probably mainly attributed to high levels of somatic mutation. Dramatic changes in range expansion in the Americas were predicted in the situation of all four genetic lineages invading the Americas or future climatic changes, especially in South America; this suggests that there is a high invasion potential of hydrilla in the Americas. Our findings provide useful information for the management of hydrilla in the Americas and give an example of exploring intraspecific climatic niche to better understand species invasion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.3072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496529PMC
July 2017

A tightly regulated IL-22 response maintains immune functions and homeostasis in systemic viral infection.

Sci Rep 2017 06 20;7(1):3857. Epub 2017 Jun 20.

Department of Microbiology and Immunology, University of Texas Medical Branch, Texas, USA.

Interleukin-22 (IL-22) plays an important role in host immunity and tissue homeostasis in infectious and inflammatory diseases. However, the function and regulation of IL-22 in viral infection remain largely unknown. Here, we report that viral infection triggered early IL-22 production from the liver and lymphoid organs. γδ T cells are the main immune cells to produce IL-22 in the liver, a process mediated by the IL-23/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. In the presence of IL-23, IL-22 production is independent of aryl hydrocarbon receptor (AhR) signaling. In acute and persistent viral infections, IL-22 deficiency resulted in thymic and splenic hypertrophy, while excessive IL-22 induced atrophy in these lymphoid organs. Moreover, IL-22 deficiency enhanced T cell responses to promote viral clearance, but increased IL-22 in vivo decreased T cell numbers and functions in the liver and lymphoid tissues. Together, our findings reveal a significant effect of the IL-23/PI3K/mTORC1 axis on regulating IL-22 production and also identify a novel role of IL-22 in controlling antiviral T cell responses in the non-lymphoid and lymphoid organs during acute and persistent viral infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-04260-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478593PMC
June 2017

Study on β-cyclodextrin-complexed nanogels with improved thermal response for anticancer drug delivery.

Mater Sci Eng C Mater Biol Appl 2017 Sep 19;78:773-779. Epub 2017 Apr 19.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, People's Republic of China. Electronic address:

For achievement of controllability in drug delivery, development of nanocarriers with thermal response is one of the most investigated stimulative strategies for oncological treatment. How to improve the thermosensitivity of the nanocarriers is an important factor for their successful drug delivery applications. In this study, a kind of complexed nanogels (PNACD) was developed by incorporating β-cyclodextrin (β-CD) into the nanogels of copolymers of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) during their polymerization via in situ crosslinking of N,N'-methylenebisacrylamide (MBA) as a crosslinker. The complexed PNACD nanogels displayed a significantly enhanced thermosensitivity near body temperature compared to the β-CD-free nanogels (PNA), which is probably associated with the rapid volumetric transformation during heating/cooling process due to the formation of complexed (decomplexed) structure between β-CD and PNIPAM element. The PNACD nanogels can be used for loading of an anticancer drug (doxorubicin, DOX) with an encapsulation efficiency of 54±5%. The DOX-loaded nanogels displayed pH-/thermo-dual responsivenesses in drug release, which can be effectively internalized into KB cells (a human epithelial carcinoma cell line) to exert good anticancer bioactivity. This approach may enlighten design of novel nanocarriers for delivery of drugs beyond anticancer chemotherapeutic reagents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2017.04.096DOI Listing
September 2017

Stimulative nanogels with enhanced thermosensitivity for therapeutic delivery via β-cyclodextrin-induced formation of inclusion complexes.

Carbohydr Polym 2017 Jun 1;166:219-227. Epub 2017 Mar 1.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China. Electronic address:

To explore the potential biomedical application of thermoresponsive nanosystems, it is important to enhance their thermosensitivity to improve the controllability in delivery of therapeutic agents. The present work develops multifunctional nanogels with enhanced thermosensitivity through copolymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of β-cyclodextrin (β-CD), using N,N'-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker. The resulting nanogels display significantly improved sensitivity in deswelling (swelling) behavior upon temperature increase (decrease) around body temperature. The nanogels can effectively encapsulate doxorubicin (DOX), which can be released in an accelerated way under microenvironments that mimic intracellular reductive conditions and acidic tumor tissues. Release can also be remotely manipulated by increasing temperature. In vitro study indicates that the nanogels are quickly taken up by KB cells (a human epithelial carcinoma cell line), exerting improved anticancer cytotoxicity, showing their potential for delivery of therapeutic agents beyond anticancer drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2017.02.107DOI Listing
June 2017

Retinoic Acid Regulates Immune Responses by Promoting IL-22 and Modulating S100 Proteins in Viral Hepatitis.

J Immunol 2017 05 31;198(9):3448-3460. Epub 2017 Mar 31.

Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070;

Although large amounts of vitamin A and its metabolite all- retinoic acid (RA) are stored in the liver, how RA regulates liver immune responses during viral infection remains unclear. In this study, we demonstrated that IL-22, mainly produced by hepatic γδ T cells, attenuated liver injury in adenovirus-infected mice. RA can promote γδ T cells to produce mTORC1-dependent IL-22 in the liver, but inhibits IFN-γ and IL-17. RA also affected the aptitude of T cell responses by modulating dendritic cell (DC) migration and costimulatory molecule expression. These results suggested that RA plays an immunomodulatory role in viral infection. Proteomics data revealed that RA downregulated S100 family protein expression in DCs, as well as NF-κB/ERK pathway activation in these cells. Furthermore, adoptive transfer of S100A4-repressed, virus-pulsed DCs into the hind foot of naive mice failed to prime T cell responses in draining lymph nodes. Our study has demonstrated a crucial role for RA in promoting IL-22 production and tempering DC function through downregulating S100 family proteins during viral hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1601891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436614PMC
May 2017

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush.

Am J Pathol 2017 Feb 10;187(2):352-365. Epub 2016 Dec 10.

Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas. Electronic address:

Traumatic optic neuropathy (TON) is an acute injury of the optic nerve secondary to trauma. Loss of retinal ganglion cells (RGCs) is a key pathological process in TON, yet mechanisms responsible for RGC death remain unclear. In a mouse model of TON, real-time noninvasive imaging revealed a dramatic increase in leukocyte rolling and adhesion in veins near the optic nerve (ON) head at 9 hours after ON injury. Although RGC dysfunction and loss were not detected at 24 hours after injury, massive leukocyte infiltration was observed in the superficial retina. These cells were identified as T cells, microglia/monocytes, and neutrophils but not B cells. CXCL10 is a chemokine that recruits leukocytes after binding to its receptor C-X-C chemokine receptor (CXCR) 3. The levels of CXCL10 and CXCR3 were markedly elevated in TON, and up-regulation of CXCL10 was mediated by STAT1/3. Deleting CXCR3 in leukocytes significantly reduced leukocyte recruitment, and prevented RGC death at 7 days after ON injury. Treatment with CXCR3 antagonist attenuated TON-induced RGC dysfunction and cell loss. In vitro co-culture of primary RGCs with leukocytes resulted in increased RGC apoptosis, which was exaggerated in the presence of CXCL10. These results indicate that leukocyte recruitment in retinal vessels near the ON head is an early event in TON and the CXCL10/CXCR3 axis has a critical role in recruiting leukocytes and inducing RGC death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2016.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389365PMC
February 2017

Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges.

J Clin Virol 2016 Apr 6;77:32-9. Epub 2016 Feb 6.

Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address:

Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive-active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2016.02.003DOI Listing
April 2016

IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice.

Eur J Immunol 2015 Nov 28;45(11):3052-63. Epub 2015 Aug 28.

Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.

Recent studies have revealed IL-33 as a key factor in promoting antiviral T-cell responses. However, it is less clear as to how IL-33 regulates innate immunity. In this study, we infected wild-type (WT) and IL-33(-/-) mice with lymphocytic choriomeningitis virus and demonstrated an essential role of infection-induced IL-33 expression for robust innate IFN-γ production in the liver. We first show that IL-33 deficiency resulted in a marked reduction in the number of IFN-γ(+) γδ T and NK cells, but an increase in that of IL-17(+) γδ T cells at 16 h postinfection. Recombinant IL-33 (rIL-33) treatment could reverse such deficiency via increasing IFN-γ-producing γδ T and NK cells, and inhibiting IL-17(+) γδ T cells. We also found that rIL-33-induced type 2 innate lymphoid cells were not involved in T-cell responses and liver injury, since the adoptive transfer of type 2 innate lymphoid cells neither affected the IFN-γ and TNF-α production in T cells, nor liver transferase levels in lymphocytic choriomeningitis virus infected mice. Interestingly, we found that while IL-33 was not required for costimulatory molecule expression, it was critical for DC proliferation and cytokine production. Together, this study highlights an essential role of IL-33 in regulating innate IFN-γ-production and DC function during viral hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.201545696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813322PMC
November 2015

Thermo/redox/pH-triple sensitive poly(N-isopropylacrylamide-co-acrylic acid) nanogels for anticancer drug delivery.

J Mater Chem B 2015 May 29;3(20):4221-4230. Epub 2015 Apr 29.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, People's Republic of China.

The clinical application of doxorubicin (DOX), like other anticancer drugs, is limited by insufficient cellular uptake and the numerous drug resistance mechanisms existing in cells. The development of smart nanomaterials capable of carrying the drugs into the cells and of releasing them under the control of the microenvironment is an interesting approach that may increase the success of the anticancer drugs currently in use. Herein, we report an easy process to prepare biocompatible nanogels (NGs) with thermo/redox/pH-triple sensitivity, which are highly effective in the intracellular delivery of DOX. Redox-sensitive/degradable NGs (PNA-BAC) and nondegradable NGs (PNA-MBA) were prepared through in situ polymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of sodium dodecyl sulfate (SDS) as a surfactant, using N,N'-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker or N,N'-methylene bisacrylamide (MBA) as a nondegradable crosslinker, respectively. After that, the cationic DOX drug was loaded into the NGs through electrostatic interactions, by simply mixing them in aqueous solution. Compared to nondegradable PNA-MBA NGs, PNA-BAC NGs not only presented a higher DOX drug loading capacity, but also allowed a more sustainable drug release behavior under physiological conditions. More importantly, PNA-BAC NGs displayed thermo-induced drug release properties and an in vitro accelerated release of DOX under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The thermo/redox/pH multi-sensitive NGs can quickly be taken up by CAL-72 cells (an osteosarcoma cell line), resulting in a high DOX intracellular accumulation and an improved cytotoxicity when compared with free DOX and DOX-loaded nondegradable PNA-MBA NGs. The developed NGs can be possibly used as an effective platform for the delivery of cationic therapeutic agents for biomedical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5tb00468cDOI Listing
May 2015