Investigating pharmacological mechanisms of andrographolide on non-alcoholic steatohepatitis (NASH): A bioinformatics approach of network pharmacology.

Objective: To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods: The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein-protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results: The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion: This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.

A retrospective study of 34 patients with unicentric and multicentric Castleman's disease: Experience from a single institution.

The aim of the present study was to share the experience of a single institute in the diagnosis, use of accessory examinations and treatment strategies of Castleman's disease (CD). The present study analyzed 34 patients (13 males and 21 females) with CD who were hospitalized between January 2006 and September 2014. The patients were divided into two groups based on the anatomical distribution of the disease: Unicentric CD (UCD) and multicentric CD (MCD). Histological data was obtained from lymph node biopsies. All clinical data were acquired by reviewing patients' medical records and contacting patients by telephone. A total of 27 patients had UCD and 7 patients had MCD. All 27 patients with UCD with benign symptoms underwent complete diagnostic surgical resection and survived, with the exception of 1 patient who succumbed to pancreatic head carcinoma 13 months after surgery. A total of 7 patients with MCD presented with systemic symptoms and 2 of these patients declined treatment following the definite diagnosis of CD. The remaining 5 patients were treated with various strategies, including surgical resection and further glucocorticoid treatment, intravenous siltuximab, rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy or hematopoietic stem cell transplantation. A total of 3 patients with MCD survived, with a median follow-up period of 69 months. The present study indicates that complete surgical resection is currently the standard treatment for UCD. Perioperative use of multidetector computed tomography and the laparoscopic approach have certain advantages in UCD. Molecular target therapy is effective in patients with stable MCD, and hematopoietic stem cell transplantation may be beneficial in certain patients with MCD and disease progression.

Neutrophil dysregulation during sepsis: an overview and update.

Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific therapy or drugs are available for sepsis. Neutrophils play a critical role in controlling infection under normal conditions, and it is suggested that their migration and antimicrobial activity are impaired during sepsis which contribute to the dysregulation of immune responses. Recent studies further demonstrated that interruption or reversal of the impaired migration and antimicrobial function of neutrophils improves the outcome of sepsis in animal models. In this review, we provide an overview of the associated mediators and signal pathways involved which govern the survival, migration and antimicrobial function of neutrophils in sepsis, and discuss the potential of neutrophils as a target to specifically diagnose and/or predict the outcome of sepsis.

Phosphatase Wip1 in Immunity: An Overview and Update.

Wild-type p53-induced phosphatase 1 (Wip1) is a newly identified serine/threonine phosphatase, which belongs to the PP2C family. Due to its involvement in stress-induced networks and overexpression in human tumors, primary studies have mainly focused on the role of Wip1 in tumorigenesis. It now has also been implicated in regulating several other physiological processes such as organism aging and neurogenesis. Recent evidence highlights a new role of Wip1 in controlling immune response through regulating immune cell development and function, as well as through the interplay with inflammatory signaling pathways such NF-κB and p38 mitogen-activated protein kinase. In this short review, we will give an overview of Wip1 in immunity to better understand this important phosphatase.

Donor-Specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac Allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival.

The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation (SBT), which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts, such as skin, kidney, and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed. To improve current mixed chimerism induction protocols for future clinical application, we developed a new protocol using donor-specific regulatory T (Treg) cells from mice with heart allograft tolerance, immunosuppressive drugs which could be used clinically and low doses of irradiation. Our results demonstrated that donor-specific Treg cells acquired from tolerant mice after in vitro expansion generate stable chimerism and lead to acceptance of intestinal allograft. Increased intragraft Treg cells and clonal deletion contribute to the development of SBT tolerance.