Icaritin Exerts Anti-Cancer Effects through Modulating Pyroptosis and Immune Activities in Hepatocellular Carcinoma.

Icaritin (ICT), a natural compound extracted from the dried leaves of the genus Epimedium, possesses antitumor and immunomodulatory properties. However, the mechanisms through which ICT modulates pyroptosis and immune response in hepatocellular carcinoma (HCC) remain unclear. This study demonstrated that ICT exhibits pyroptosis-inducing and anti-hepatocarcinoma effects.

SARS-CoV-2 Papain-like Protease Negatively Regulates the NLRP3 Inflammasome Pathway and Pyroptosis by Reducing the Oligomerization and Ubiquitination of ASC.

The interaction of viruses with hosts is complex, especially so with the antiviral immune systems of hosts, and the underlying mechanisms remain perplexing. Infection with may result in cytokine syndrome in the later stages, reflecting the activation of the antiviral immune response. However, viruses also encode molecules to negatively regulate the antiviral immune systems of hosts to achieve immune evasion and benefit viral replication during the early stage of infection.

A comprehensive analysis of Usutu virus (USUV) genomes revealed lineage-specific codon usage patterns and host adaptations.

The Usutu virus (USUV) is an emerging arbovirus virus maintained in the environment of Afro-Eurasia a bird-mosquito-bird enzootic cycle and sporadically infected other vertebrates. Despite primarily asymptomatic or mild symptoms, humans infected by USUV can develop severe neurological diseases such as meningoencephalitis. However, no detailed study has yet been conducted to investigate its evolution from the perspective of codon usage patterns.

Syntheses and Structure-Activity Relationships in Antibacterial Activity against Clostridium difficile and XBP1 Activation Property of 13-[(N-Alkylamino)methyl]-8-oxodihydrocoptisines.

13-[(N-Alkylamino)methyl]-8-oxodihydrocoptisines were synthesized to evaluate antibacterial activity against Clostridium difficile and activating x-box-binding protein 1 (XBP1) activity, biological properties both associated with ulcerative colitis. Improving structural stability and ameliorating biological activity were major concerns. Different substituents on the structural modification site were involved to explore the influence of diverse structures on the bioactivities.

MCPIP1 negatively regulate cellular antiviral innate immune responses through DUB and disruption of TRAF3-TBK1-IKKε complex.

IFNβ innate immune plays an essential role in antiviral immune. Previous reports suggested that many important regulatory proteins in innate immune pathway may be modified by ubiquitin and that many de-ubiquitination (DUB) proteins may affect immunity. Monocyte chemotactic protein-inducing protein 1 (MCPIP1), one of the CCCH Zn finger-containing proteins, was reported to have DUB function, but its effect on IFNβ innate immune was not fully understood.

Autophagy relieves the function inhibition and apoptosis‑promoting effects on osteoblast induced by glucocorticoid.

Autophagy may be a major mechanism by which osteoblasts (OBs) protect against the negative effects of chronic glucocorticoid (GC) usage. OBs are closely associated with the remodeling that occurs in GC‑induced osteoporosis (GIO). In osteocytes, in response to stress induced by GCs, several pathways are activated, including cell necrosis, apoptosis and autophagy.

Radiation protective effects of baclofen predicted by a computational drug repurposing strategy.

Exposure to ionizing radiation causes damage to living tissues; however, only a small number of agents have been approved for use in radiation injuries. Radioprotector is the primary countermeasure to radiation injury and none radioprotector has indeed reached the drug development stage. Repurposing the long list of approved, non-radioprotective drugs is an attractive strategy to find new radioprotective agents.

Clinical characteristics and prognosis of primary pancreatic carcinoid tumors: A report of 13 cases from a single institution.

The present study aimed to analyze the diagnosis and treatment of 13 cases of pancreatic carcinoid tumors during a 56-year period at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The data from 13 cases, consisting of 5 males and 8 females (mean age, 50 years), were collected and analyzed. Hematoxylin-eosin and immunohistochemistry staining were performed to investigate the expression of neuron-specific enolase (NSE), cytokeratin (CK), chromogranin A (CgA) and synaptophysin (Syn) in the tumors.

Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity.

Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 (PLP2-TM) of coronaviruses acts as a novel autophagy-inducing protein.

SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway.

Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease.

The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood.

5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells.

Hepatitis B virus (HBV) infection often results in acute or chronic viral hepatitis and other liver diseases including cirrhosis and hepatocellular carcinoma. Current therapies for HBV usually have severe side effects and can cause development of drug-resistant mutants. An alternative and safe immunotherapeutic approach for HBV infection is urgently needed for effective anti-HBV therapy.

5'-triphosphate-siRNA against survivin gene induces interferon production and inhibits proliferation of lung cancer cells in vitro.

Survivin is a new member of the inhibitors of apoptosis family and upregulated in various human malignancies including human lung cancer. In this study, we proposed a new strategy for RNA interference (RNAi)-mediated anticancer therapy combining activation of interferon production with RNAi using 5'-triphosphate-siRNA (3p-siRNA) against survivin gene. We designed and generated 3p-siRNA targeting human survivin gene (3p-survivin-siRNA).

The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase.

Porcine epidemic diarrhea virus (PEDV) is the cause of an economically important swine disease. Previous studies suggested that PEDV does not elicit a robust IFN response, but the mechanism(s) used to evade or block this innate immune response was not known. In this study, we found that PEDV infection blocked synthetic dsRNA-induced IFN-β production by interfering with the activation of interferon regulatory factor 3 (IRF3).

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist.

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application.

Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling.

Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN).

Protocatechuic aldehyde inhibits lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis via regulation of caspase-3.

Apoptosis of vascular endothelial cells results in the loss of endothelial integrity, and is a risk factor of atherosclerosis (AS). Lipopolysaccharide (LPS) stimulates inflammation during AS. The current study examined the effect of a potent water-soluble antioxidant, protocatechuic aldehyde (PCA; derived from the Chinese herb Salvia miltiorrhiza) on apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated with LPS.

S-Nitrosylation of mitogen activated protein kinase phosphatase-1 suppresses radiation-induced apoptosis.

Radiotherapy is a key modality for head and neck cancer (HNC) treatment. Mitogen activated protein kinase phosphatase-1 (MKP-1) protein levels are elevated in various tumors and are negatively correlated with efficacy of chemo- or radio-therapy. However, the mechanisms underlying the moderate radiosensitivity of HNC and the increased MKP-1 protein levels are still dismal.

WITHDRAWN: Tanshinone IIA protects rat cardiomyocytes against apoptosis induced by angiotensin II in vitro.

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Salvianolic acid B, an antioxidant from Salvia miltiorrhiza, prevents 6-hydroxydopamine induced apoptosis in SH-SY5Y cells.

Oxidative stress caused by dopamine may play an important role in the pathogenesis of Parkinson's disease. Salvianolic acid B is an antioxidant derived from the Chinese herb, Salvia miltiorrhiza. In this study, we investigated the neuroprotective effect of salvianolic acid B against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells.