Autophagy and cancer therapy.

Autophagy is an intracellular degradation process that sequesters cytoplasmic components in double-membrane vesicles known as autophagosomes, which are degraded upon fusion with lysosomes. This pathway maintains the integrity of proteins and organelles while providing energy and nutrients to cells, particularly under nutrient deprivation. Deregulation of autophagy can cause genomic instability, low protein quality, and DNA damage, all of which can contribute to cancer.

Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OX neurons).

The role of the immune response and inflammatory pathways in TNF-related apoptosis-inducing ligand (TRAIL) resistance in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, and the majority of TNBC lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to TNF-related apoptosis-inducing ligand (TRAIL), making it a potentially viable treatment option for TNBC. However, the development of TRAIL resistance limits its potential for clinical use, and the underlying mechanisms are not fully understood.

The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that selectively induces apoptosis in tumor cells without harming normal cells, making it an attractive agent for cancer therapy. TRAIL induces apoptosis by binding to and activating its death receptors DR4 and DR5. Several TRAIL-based treatments have been developed, including recombinant forms of TRAIL and its death receptor agonist antibodies, but the efficacy of TRAIL-based therapies in clinical trials is modest.

Donor-Derived Transmission of Scedosporiosis in Kidney Transplant Recipients from a Systemic lupus erythematosus donor.

Donor-derived infection (DDI) associated with Scedosporium spp is extremely rare, and results in a very poor prognosis. The present study reports a probable DDI due to Scedosporium boydii (S. boydii) from a donor with neuropsychiatric systemic lupus erythematosus.

Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), making it a promising agent for treating TNBC. However, the development of TRAIL resistance limits its further clinical development, and the underlying mechanisms are not fully understood.

Proteomic Analysis Identifies p62/SQSTM1 as a Critical Player in PARP Inhibitor Resistance.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) are currently being used for treating breast cancer patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic diseases. Despite durable responses, almost all patients receiving PARPis ultimately develop resistance and succumb to their illness, but the mechanism of PARPi resistance is not fully understood. To better understand the mechanism of PARPi resistance, we established two olaparib-resistant SUM159 and MDA468 cells by chronically exposing olaparib-sensitive SUM159 and MDA468 cells to olaparib.

First case of Shewanella indica isolated from a Bryde's whale (Balaenoptera edeni) stranded in the northern Beibu Gulf, China.

The purpose of this study was to culture and characterise bacteria from an intact abscess on the skin of a dead Bryde's whale (Balaenoptera edeni) which stranded in the northern Beibu Gulf, China. To grow bacteria, samples from the abscess were added to blood agar. After incubation, yellowish mucous colonies were visualized.

Alcohol consumption analysis among patients with liver disease in China.

Background: Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking.

Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy.

Accumulating evidence suggests that mitogen-activated protein kinases (MAPKs) regulate macroautophagy/autophagy. However, the involvement of dual-specificity protein phosphatases (DUSPs), endogenous inhibitors for MAPKs, in autophagy remains to be determined. Here we report that DUSP1/MKP-1, the founding member of the DUSP family, plays a critical role in regulating autophagy.

The Role of Ceramide in the Pathogenesis of Alcoholic Liver Disease.

Aims: Ceramide is an important second messenger in the sphingomyelin signaling pathway. In this review, we will focus on the potential role of ceramide in the pathogenesis of alcoholic liver disease (ALD).

Methods: We have summarized the relevant studies and reviews about the role of ceramide in ALD.

The role of DCs in the immunopathogenesis of chronic HBV infection and the methods of inducing DCs maturation.

Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Dendritic cells (DCs), as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation. DCs of patients with chronic HBV infection are impaired, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence.

The adiponectin-SIRT1-AMPK pathway in alcoholic fatty liver disease in the rat.

Background: Our previous work showed that binge drinking in the rat induced hepatic steatosis which correlated with reduced expression of AMP-activated protein kinase (AMPK). In this study, we used the rat model to investigate the role of adiponectin (Adip), sirtuin 1 (SIRT1), AMPK, and lipin 1 (LIP 1) signaling, a central controlling pathway of lipid metabolism in hepatic steatosis.

Methods: The serum Adip and tumor necrosis factor-alpha (TNF-α) as well as liver Adip receptors (AdipoR1 and AdipoR2) SIRT1, AMPK, phosphorylated AMPK (p-AMPK), sterol regulatory element-binding proteins (SREBPs), acetyl-CoA carboxylase (ACC), LIP 1, lipocalin-2 (LCN2), and serum amyloid A1 were assessed in the rat model where 16 weeks of gavaged alcohol were administered.

The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling.

Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase that regulates a number of cell signaling pathways. PP2A activity is controlled partially through protein degradation; however, the underlying mechanism is not fully understood. Here we show that PP2A/C, a catalytic subunit of PP2A, is degraded by the Cullin3 (Cul3) ligase-mediated ubiquitin-proteasome pathway.

Involvement of insulin resistance in the protective effect of metformin against alcoholic liver injury.

Background: Alcoholic liver disease (ALD) continues to be a major cause of morbidity worldwide. The exact mechanisms for ALD pathogenesis are not fully understood. There is currently no known available drug for ALD.

[Dynamic changes in programmed death-1 expression on the surface of T cells in chronic hepatitis C patients undergoing interferon therapy].

Objective: To investigate the dynamic changes that occur in T cell subsets, particularly involving the surface expression of programmed death 1 (PD-1), in response to pegylated (Peg)-interferon (IFN) a-2a therapy in patients with chronic hepatitis C virus (HCV) infection.

Methods: Twenty-five patients with HCV genotype 1b chronic infection and 10 healthy controls were enrolled in the study. All the HCV patients received combination antiviral therapy of Peg-IFNa-2a (180 mug/week) plus ribavirin.

Regulation of the Src-PP2A interaction in tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in transformed and tumor cells but not in normal cells, making it a promising agent for cancer therapy. However, many cancer cells are resistant to TRAIL, and the underlying mechanisms are not fully understood. Here, we show that the regulation of the PP2A and Src interaction plays a critical role in TRAIL resistance.

[PD-1 expression in HBcAg-specific CD8+ T cells of adolescents with chronic HBV infection].

Objective: To investigate the differential expression of programmed death-1 (PD-1) in the hepatitis B core antigen (HBcAg)17-28-specific CD8+ T cell subsets of adolescent patients with chronic hepatitis B virus (HBV) infection during the immune tolerant phase and the immune clearance phase.

Methods: A total of 105 patients between the ages of 12-28 years old (mean age 17.20+/-6.

Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.

Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10.

Virological responses in chronic hepatitis C patients undergoing prolonged therapy with low-dose Peg-IFNα-2a.

Background/aims: Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy.

Methodology: Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a.

Long-term binge and escalating ethanol exposure causes necroinflammation and fibrosis in rat liver.

Background: To investigate whether "binge" and escalating alcohol exposure in the rat influences the development of pathological liver injury.

Methods: Time courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative stress and nitrosative stress production, expression of hypoxia-inducible factor 1 (HIF-1), cytokines, hepatic tissue necroinflammation, and fibrosis were assessed in rats during 16 weeks of daily alcohol gavage.

Results: In this model of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and inflammation as well as fibrosis were increased over the 16-week period.

The acute effects of levetiracetam on nocturnal sleep and daytime sleepiness in patients with partial epilepsy.

This study investigated the effect of the novel antiepileptic drug levetiracetam (LEV) on sleep in eleven patients with partial epilepsy. At baseline and one week after therapy with LEV (1000 mg/day), patients underwent polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT). Patients also rated their own degree of sleep disturbance and daytime sleepiness with the Athens Insomnia Scale (AIS) and the Epworth Sleepiness Scale (ESS).