Transcriptome dynamics of the BHK21 cell line in response to human coronavirus OC43 infection.

The progress of viral infection involves numerous transcriptional regulatory events. The identification of the newly synthesized transcripts helps us to understand the replication mechanisms and pathogenesis of the virus. Here, we utilized a time-resolved technique called metabolic RNA labeling approach called thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) to differentially elucidate the levels of steady-state and newly synthesized RNAs of BHK21 cell line in response to human coronavirus OC43 (HCoV-OC43) infection.

Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance.

The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune landscape of spontaneous liver tolerance throughout the rejection and acceptance stages after liver transplantation and highlighted several points of importance.

CD93 overexpresses in liver hepatocellular carcinoma and represents a potential immunotherapy target.

Background: Liver hepatocellular carcinoma (LIHC) is one of the malignant tumors with high incidence as well as high death, which is ranked as the sixth most common tumor and the third highest mortality worldwide. CD93, a transmembrane protein, has been widely reported to play an important role in different types of diseases, including many types of cancer by mainly functioning in extracellular matrix formation and vascular maturation. However, there are few researches focusing on the role and potential function of CD93 in LIHC.

Combinations of anti-GITR antibody and CD28 superagonist induce permanent allograft acceptance by generating type 1 regulatory T cells.

Type 1 regulatory T (Tr1) cells represent a subset of IL-10-producing CD4Foxp3 T cells and play key roles in promoting transplant tolerance. However, no effective pharmacological approaches have been able to induce Tr1 cells in vivo. We herein report the combined use of a CD28 superagonist (D665) and anti-glucocorticoid-induced tumor necrosis factor receptor-related protein monoclonal antibody (G3c) to induce Tr1 cells in vivo.

Characteristics of changes in double positive CD4CD8 T cells in liver transplantation.

Although double positive CD4CD8 T (DPT) cells has been reported to be involved in some diseases, their trajectory and function as associated with liver transplantation (LT) remain unclear. In the present study, we found that the number of DPT cells was increased in the blood and liver tissue of LT patients. Meanwhile, we compared the distribution of DPT cells in peripheral blood samples and in penetrating liver tissue between liver rejection versus non-rejection patients, as well as the proportion of DPT cells as a function of the extent of liver rejection.

Hepatic pannexin-1 mediates ST2 regulatory T cells promoting resolution of inflammation in lipopolysaccharide-induced endotoxemia.

Sepsis remains the most lethal infectious disease and substantially impairs patient prognosis after liver transplantation (LT). Our previous study reported a role of the pannexin 1 (PANX1)-interleukin-33 (IL-33) axis in activating innate immunity to protect against methicillin-resistant Staphylococcus aureus infection; however, the role of PANX1 in regulating adaptive immunity in sepsis and the underlying mechanism are unclear. In this study, we examined the role of the PANX1-IL-33 axis in protecting against sepsis caused by a gram-negative bacterial infection in an independent LT cohort.

Combinations of anti-GITR antibody and CD28 superagonist ameliorated dextran sodium sulfate-induced mouse colitis.

Ulcerative colitis (UC) is one of the two main forms of inflammatory bowel disease (IBD) and is an idiopathic, chronic inflammatory disease of the colonic mucosa with an unclear etiology. Interleukin (IL)-10 has been reported to play a crucial role in the maintenance of immune homeostasis in the intestinal environment. Type 1 regulatory T (Tr1) cells are a subset of CD4+Foxp3- T cells able to secrete high amounts of IL-10 with potent immunosuppressive properties.

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.

CD4CD25 regulatory T cells (Tregs), a subpopulation of naturally CD4 T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse.

Oridonin Prolongs the Survival of Mouse Cardiac Allografts by Attenuating the NF-κB/NLRP3 Pathway.

Background: Oridonin (Ori), the main bioactive ingredient of the natural anti-inflammatory herb , could be a covalent inhibitor of the NLRP3 inflammasome. Solid organ transplantation provides a life-saving optional therapy for patients with end-stage organ dysfunction. The long-term survival of solid organ transplantation remains restricted because of the possibility of rejection and the toxicity, infection, cardiovascular disease, and malignancy related to immunosuppressive (IS) drugs.

A Mesenchymal-Epithelial Transition Factor-Agonistic Antibody Accelerates Cirrhotic Liver Regeneration and Improves Mouse Survival Following Partial Hepatectomy.

Small-for-size syndrome (SFSS) is a common complication following partial liver transplantation and extended hepatectomy. SFSS is characterized by postoperative liver dysfunction caused by insufficient regenerative capacity and portal hyperperfusion and is more frequent in patients with preexisting liver disease. We explored the effect of the Mesenchymal-epithelial transition factor (MET)-agonistic antibody 71D6 on liver regeneration and functional recovery in a mouse model of SFSS.

Liver injury in COVID-19: Detection, pathogenesis, and treatment.

In the early December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China, followed by an outbreak that spread around the world. Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019 (COVID-19), and may aggravate the severity of the disease. However, the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further.

Recipient C7 rs9292795 genotype and the risk of hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population.

Background: Complement component(C7) gene has been shown to influence the prognosis in Hepatocellular carcinoma (HCC) patients. The association between C7 and HCC recurrence after orthotopic liver transplantation (OLT), however, is still unknown. The purpose of this study was to evaluate whether the donor and recipient C7 gene polymorphisms are related to HCC recurrence after OLT in the Han Chinese population.

5-Aminolevulinic acid/sodium ferrous citrate enhanced the antitumor effects of programmed cell death-ligand 1 blockade by regulation of exhausted T cell metabolism in a melanoma model.

Mitochondria are key cytoplasmic organelles. Their activation is critical for the generation of T cell proliferation and cytotoxicity. Exhausted tumor-infiltrating T cells show a decreased mitochondrial function and mass.

Monotherapy With Anti-CD70 Antibody Causes Long-Term Mouse Cardiac Allograft Acceptance With Induction of Tolerogenic Dendritic Cells.

Allograft rejection has been an obstacle for the long-term survival of patients. CD70, a tumor necrosis factor (TNF) family member critically expressed on antigen-presenting cells and strongly but transiently up-regulated during lymphocyte activation, represents an important co-stimulatory molecule that induces effective T cell responses. We used a mouse heterotopic cardiac transplantation model to evaluate the effects of monotherapy with the antibody targeting mouse CD70 (FR70) on transplantation tolerance and its immunoregulatory activity.

Regulatory T Cells for the Induction of Transplantation Tolerance.

Organ transplantation is the optimal treatment for terminal and irreversible organ failure. Achieving transplantation tolerance has long been the ultimate goal in the field of transplantation. Regulatory T cell (Treg)-based therapy is a promising novel approach for inducing donor organ-specific tolerance.

Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling.

Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis in the absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with a high concentration of hydrogen, namely, hydrogen-rich water (HRW), on mice with nonalcoholic fatty liver disease to elucidate the mechanism underlying the therapeutic action of molecular hydrogen. The choline-supplemented, l-amino acid-defined (CSAA) or the choline-deficient, l-amino acid-defined (CDAA) diet for 20 wk was used to induce NASH and fibrosis in the mice model and simultaneously treated with the high-concentration 7-ppm HRW for different periods (4 wk, 8  wk, and 20 wk).

5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC1-α activation.

Acute graft-versus-host disease (aGvHD) remains lethal as a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Inflammatory responses play an important role in aGvHD. 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) has been widely reported to have a major effect on the anti-inflammatory response; however, these effects in aGvHD models have never been reported.

Manipulation of Regulatory Dendritic Cells for Induction Transplantation Tolerance.

Current organ transplantation therapy is life-saving but accompanied by well-recognized side effects due to post-transplantation systematic immunosuppressive treatment. Dendritic cells (DCs) are central instigators and regulators of transplantation immunity and are responsible for balancing allograft rejection and tolerance. They are derived from monocyte-macrophage DC progenitors originating in the bone marrow and are classified into different subsets based on their developmental, phenotypical, and functional criteria.

The Role of Diverse Liver Cells in Liver Transplantation Tolerance.

Liver transplantation is the ideal treatment approach for a variety of end-stage liver diseases. However, life-long, systemic immunosuppressive treatment after transplantation is required to prevent rejection and graft loss, which is associated with severe side effects, although liver allograft is considered more tolerogenic. Therefore, understanding the mechanism underlying the unique immunologically privileged liver organ is valuable for transplantation management and autoimmune disease treatment.

Immunomodulatory effects of Salvianolic acid B in a spontaneous abortion mouse model.

Pregnancy is a kind of natural immune tolerance. Immune factors play an important role in recurrent spontaneous abortion and repeated implantation failure. Salvianolic acid B (SalB) has anti-tumor, anti-inflammatory, anti-oxidation and immunomodulatory functions.

Prolonged Cold Ischemia Time in Mouse Heart Transplantation Using Supercooling Preservation.

Background: Supercooling preservation techniques store a donor organ below 0°C without freezing. This has great advantages in inhibiting metabolism and preserving the organ in comparison to conventional preservation at 4°C. We developed a novel supercooling technique using a liquid cooling apparatus and novel preservation and perfusion solutions.

Salvianolic acid B ameliorates liver injury in a murine aGvHD model by decreasing inflammatory responses via upregulation of HO-1.

Acute graft-versus-host disease (aGvHD) remains lethal, even after allogeneic hematopoietic stem cell transplantation. Inflammatory responses play an important role in aGvHD. Salvianolic acid B (Sal B) has been widely reported to have a major effect on the anti-inflammatory response, but these effects in an aGvHD model have never been reported.

Application of 3-Dimensional Printing in Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

Three-dimensional (3D) printing has been used to support organ transplantations. However, whether it helps remains unclear. This study aimed to present and assess the application of 3D-printed liver models in pediatric living donor liver transplantation (LDLT).

Hydrogen-rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation.

Background: Liver transplantation (LT) is considered the standard treatment for end-stage liver disease, but ideal donors remain in limited supply, resulting in an unavoidable increase in the need to use grafts from marginal donors. The attenuation of ischemia-reperfusion injury (IRI) in such marginal donors is therefore crucial for reducing the possibility of the primary non-function of grafts and graft loss. Some reports have found that molecular-hydrogen showed antioxidant and anti-inflammatory effects in preventing IRI in some non-hepatic transplant models.

Myeloid heme oxygenase-1: a new therapeutic target in anti-inflammation.

An increasing amount of evidence reveals that an orchestrated interplay between myeloid subpopulations in the hematopoietic system plays a significant role in supporting normal functions of the immune system and facilitating homeostatic restoration upon exogenous or endogenous insults. Heme oxygenase-1 (HO-1), a microsomal enzyme discovered decades ago, can metabolize pro-oxidant heme into biliverdin, free iron, and carbon monoxide. This enzymatic reaction produces biological materials, contributing to major immunomodulatory effects.