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Hepatitis AND Immunomod*

Xiang Yu, Lu Chen, Jianqiao Liu, Bolei Dai, Guoqiang Xu, Guanxin Shen, Qingming Luo, Zhihong Zhang
Liver sinusoidal endothelial cells (LSECs) are responsible for the immunologic tolerance of liver which is a common site for visceral metastases, suggesting its potential role as an target for cancer immunotherapy. However, targeted modulation of LSECs is still not achieved thus far. Here, we report LSECs are specifically targeted and modulated by melittin nanoparticles (α-melittin-NPs). Intravital imaging shows that LSECs fluoresce within 20 s after intravenous injection of α-melittin-NPs. α-melittin-NPs trigger the activation of LSECs and lead to dramatic changes of cytokine/chemokine milieu in the liver, which switches the hepatic immunologic environment to the activated state...
February 4, 2019: Nature Communications
Zuotian Huang, Daofeng Zheng, Junliang Pu, Jiangwen Dai, Yuchi Zhang, Wanqiu Zhang, Zhongjun Wu
MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups...
January 27, 2019: Bioscience, Biotechnology, and Biochemistry
D C Cai, H Ren
Since the 40th anniversary of China's reform and opening-up, earth-shattering development has taken place in all walks of life across the country. Research field on the prevention and treatment of chronic hepatitis B has been rewarding after 40 years of trials and tribulations. Additionally, hepatitis B vaccination program and effective antiviral therapy has amazingly reduced the prevalence of hepatitis B virus infection. Coupled with the literary evidence, a consensus has gradually emerged in the field of anti-HBV treatment that "high potency, low incidence of drug resistance and immunomodulation coexists"...
January 20, 2019: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Asli Haykir Solay, Fatma Eser
In patients undergoing immunotherapy, the quality of the immune response is reduced, which may negatively affect the efficacy of vaccination. This study was conducted in order to evaluate the efficacy of the hepatitis B virus (HBV) vaccine in patients using immunomodulators. Seronegative patients for HBV who were using biological agents, were included in the study. The vaccination was administered on the standard schedule in 3 doses of 20 or 40 µg/ml. Eighty-two patients (52%) were males and the mean age of all patients was 44,8 ± 10,3 years...
January 24, 2019: Human Vaccines & Immunotherapeutics
Zhipeng Yan, Daitze Wu, Hui Hu, Jing Zeng, Xin Yu, Zhiheng Xu, Zheng Zhou, Xue Zhou, Guang Yang, John A T Young, Lu Gao
Hepatitis B e antigen (HBeAg) is an important immunomodulator for promoting host immune tolerance during chronic hepatitis B (CHB) infection. In CHB patients, HBeAg loss and seroconversion represent partial immune control of CHB infection and are regarded as valuable endpoints. However, the current approved treatments have only a limited efficacy in achieving HBeAg seroconversion in HBeAg-positive patients. HBV core protein has been recognized as an attractive antiviral target and two classes of core protein allosteric modulator (CpAM) have been discovered: the phenylpropenamides (PPAs) and the heteroaryldihydropyrimidines (HAPs)...
January 21, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yufang Ding, Karin Yanagi, Clint Cheng, Robert C Alaniz, Kyongbum Lee, Arul Jayaraman
There is increasing evidence that the intestinal microbiota plays a mechanistic role in the etiology of non-alcoholic fatty liver disease (NAFLD). Animal and human studies have linked small molecule metabolites produced by commensal bacteria in the gut contribute to not only intestinal inflammation, but also to hepatic inflammation. These immunomodulatory metabolites are capable of engaging host cellular receptors, and may mediate the observed association between gut dysbiosis and NAFLD. This review focuses on the effects and potential mechanisms of three specific classes of metabolites that synthesized or modified by gut bacteria: short chain fatty acids, amino acid catabolites, and bile acids...
January 17, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Malte P Suppli, Kristoffer T G Rigbolt, Sanne S Veidal, Sara Heebøl, Peter Lykke Eriksen, Mia Demant, Jonatan I Bagger, Jens Christian Nielsen, Denise Oró, Sebastian W Thrane, Asger Lund, Charlotte Strandberg, Merete J Kønig, Tina Vilsbøll, Niels Vrang, Karen Louise Thomsen, Henning Grønbæk, Jacob Jelsing, Henrik H Hansen, Filip K Knop
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over non-alcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared to healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis was performed on liver biopsies obtained from healthy normal weight (n=14) and obese (n=12) individuals, NAFL (n=15) and NASH (n=16) patients...
January 17, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Yehudit Shabat, Ami Ben Ya'acov, Yaron Ilan
Background and Aims: The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen -induced liver damage. Methods: AAT was administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage...
December 28, 2018: Journal of Clinical and Translational Hepatology
Zeinab Zarei Behjani, Jafar Ai, Masoud Soleimani, Amir Atashi, Behnaz Taheri, Somayeh Ebrahimi-Barough, Vahid Siavashi, Sadegh Shirian, Amir Ali Hamidieh
Sepsis and related disorders, especially acute lung injury (ALI), are the most challenging life-threatening diseases in the hospital intensive care unit. Complex pathophysiology, unbalanced immune condition, and high rate of mortality complicate the treatment of sepsis. Recently, cell therapy has been introduced as a promising option to recover the sepsis symptoms. The aim of this study was to investigate the therapeutic potential of human unrestricted somatic stem cells (USSCs) isolated from human umbilical cord blood in the mouse model of ALI...
January 9, 2019: Journal of Cellular Physiology
Débora Raquel Benedita Terrabuio, Marcio Augusto Diniz, Lydia Teofilo de Moraes Falcão, Ana Luiza Vilar Guedes, Larissa Akeme Nakano, Andréia Silva Evangelista, Fabiana Roberto Lima, Clarice Pires Abrantes-Lemos, Flair José Carrilho, Eduardo Luiz Rachid Cancado
Between 50% and 86% of patients with autoimmune hepatitis (AIH) relapse after immunosuppression withdrawal; long-term immunosuppression is associated with increased risk of neoplasias and infections. Chloroquine diphosphate (CQ) is an immunomodulatory drug that reduces the risk of flares in rheumatologic diseases. Our aims were to investigate the efficacy and safety of CQ for maintenance of biochemical remission of AIH in a double-blind randomized trial and to define a subgroup that obtained a greater benefit from its use...
January 2019: Hepatology Communications
Zhujin Ding, Xiaoheng Zhao, Jixiu Wang, Feng Zhang, Weimin Wang, Hong Liu
Intelectin, a lectin discovered recently, has been identified in various vertebrate species, such as fish, amphibians, and mammals. In one of our previous studies, the efficient bacteria binding and agglutinating activity of the recombinant Megalobrama amblycephala intelectin protein (rMamINTL) and the enhanced immunopositive localization have been observed in the hepatic macrophage-like cells (kupffer cells) post Aeromonas hydrophila infection. Thus, the present study primarily focuses on the regulatory effects of rMamINTL on M...
January 4, 2019: Fish & Shellfish Immunology
Eirini I Rigopoulou, Sofia Gyftaki, Pinelopi Arvaniti, Vana Tsimourtou, George K Koukoulis, Georgios Hadjigeorgiou, George N Dalekos
BACKGROUND: Development of autoimmune hepatitis (AIH) has been sporadically reported in patients with multiple sclerosis (MS) either concurrently or after treatment with immunomodulatory drugs, including interferon-beta (IFN-β) and steroids. AIM: To report a large cohort of 14 patients with MS diagnosed with AIH during an assessment of deranged liver function tests (LFTs). PATIENTS AND METHODS: From 2005 to 2017, we prospectively identified 14 (13 women) patients with MS who suffered also from AIH after investigation in our department for the presence of deranged LFTs...
December 26, 2018: Clinics and Research in Hepatology and Gastroenterology
Man Luo, Hong Peng, Ping Chen, Yong Zhou
Fibrosis makes numerous diseases in all organs more complicated and leads to severe consequences in the lung, liver, heart, kidney and skin. In essence, fibrosis results from excessive, persistent and oftentimes nonreversible aggregation of extracellular matrix (ECM) or simply as collagen during the process of tissue injury and repair. Recent studies suggest the pathology of fibrosis, especially in pulmonary and liver fibrosis, involves various types of immune cells and soluble mediators including interleukin (IL)-35, a recently identified heterodimeric cytokine that belongs to the IL-12 cytokine family...
December 27, 2018: Expert Review of Clinical Immunology
Scott M Rowley
CASE STUDY RS, a 36-year-old female, presented to the emergency department (ED) of a large academic medical center upon the advice of her primary care provider because of 3 weeks of progressive mental status changes, weakness, and decreased oral intake. According to her husband, RS was diagnosed with stage IIIA large cell lung cancer 8 months earlier and was treated with concurrent chemotherapy (carboplatin, pemetrexed, and bevacizumab) and radiation therapy that was completed 4 months prior to admission. No other specific information about her treatment or outside health records was available...
March 2018: Journal of the Advanced Practitioner in Oncology
Asmita Pramanik, Dibyendu Paik, Pijush Kanti Pramanik, Tapati Chakraborti
Leishmaniasis is a parasite-mediated tropical disease affecting millions of individuals worldwide. The available antileishmanial chemotherapeutic modalities exhibit adverse toxicity, exorbitant price and advent of drug-resistant parasites. Hence, plant-derived products are an alternative preference for the emergence of novel and effective antileishmanial agents that rejuvenate the host immunity with limited toxicity. The present work is complementary to our previous report that revealed the in vitro antileishmanial and immunomodulatory activity of Coccinia grandis (L...
December 21, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Andrew D Huber, Dallas L Pineda, Dandan Liu, Kelsey N Boschert, Anna T Gres, Jennifer J Wolf, Emily M Coonrod, Jing Tang, Thomas G Laughlin, Qiongying Yang, Maritza Puray-Chavez, Juan Ji, Kamlendra Singh, Karen A Kirby, Zhengqiang Wang, Stefan G Sarafianos
An estimated 240 million are chronically infected with hepatitis B virus (HBV), which can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Currently, HBV treatment options include only nucleoside reverse transcriptase inhibitors and the immunomodulatory agent interferon alpha, and these treatments are generally not curative. New treatments with novel mechanisms of action, therefore, are highly desired for HBV therapy. The viral core protein (Cp) has gained attention as a possible therapeutic target because of its vital roles in the HBV life cycle...
December 24, 2018: ACS Infectious Diseases
A Rodrigues, G Alexandre-Pires, A Valério-Bolas, D Santos-Mateus, M Rafael-Fernandes, M A Pereira, D Ligeiro, T Nunes, R Alves-Azevedo, S Lopes-Ventura, M Santos, A M Tomás, I Pereira da Fonseca, G Santos-Gomes
Hepatocytes constitute the majority of hepatic cells, and play a key role in controlling systemic innate immunity, via pattern-recognition receptors (PRRs) and by synthesizing complement and acute phase proteins. Leishmania infantum, a protozoan parasite that causes human and canine leishmaniasis, infects liver by establishing inside the Kupffer cells. The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to L. infantum. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed...
December 18, 2018: Parasitology
Zhaoyan Kong, Rong Liu, Yuanrong Cheng
Liver fibrosis is a progression of chronic liver disease, which lacks effective therapies in the world. Attractively, more and more evidences show that natural products are safe and effective in the prevention and treatment of hepatic fibrosis. Artesunate, a water-soluble hemisuccinate derivative of artemisinin, exerts various pharmacological activities such as anti-inflammatory, anti-tumor and immunomodulating abilities. However, the effects of artesunate on hepatic fibrosis are little-known. Here our study was performed to investigate the effect of artesunate on carbon tetrachloride (CCl4 )-induced mouse liver fibrosis and elucidate whether artesunate could alleviate liver fibrosis by regulating ferritinophagy- mediated ferroptosis in hepatic stellate cells (HSCs)...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Irina G Danilova, Boris G Yushkov, Irina A Kazakova, Anna V Belousova, Artem S Minin, Musa T Abidov
Pharmacological interventions which could be hepatoprotective, depending on bioavailability, anti-inflammatory and macrophage-targeting potential of drugs, are still at early preclinical stages. Existing evidence from many animal models of liver injury, as well as from human data, indicate that pharmacological and/or phytochemical interventions have limited impact on liver recovery. Recent studies on stem cell therapies focused on different cell subsets involved in tissue repair, including monocytes/macrophages and bone marrow cells migrating to the injured liver...
December 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bharati Kochar, Hans H Herfarth
Background: Patients with moderate-severe inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are commonly treated with long-term immunosuppressive therapies involving immunomodulators such as thiopurines, biologics (anti-TNF and anti-adhesion molecules), or novel small molecules such as Janus kinase inhibitors. Summary: Some infections seen with immunosuppressive therapy in IBD are preventable with vaccines. IBD-specific immunosuppressive therapy is generally initiated by gastroenterologists...
November 2018: Inflammatory Intestinal Diseases
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