Jiancong Lin

Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells.

A number of studies have demonstrated that inflammation plays a role in doxorubicin (DOX)-induced cardiotoxicity. However, the molecular mechanism by which DOX induces cardiac inflammation has yet to be fully elucidated. The present study aimed to investigate the role of the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in DOX-induced inflammation and cytotoxicity. The results of our study demonstrated that the exposure of H9c2 cardiac cells to DOX reduced cell viability and stimulated an inflammatory response, as demonstrated by an increase in the levels of interleukin-1β (IL-1β) and IL-6, as well as tumor necrosis factor-α (TNF-α) production. Notably, DOX exposure induced the overexpression of phosphorylated p38 MAPK and phosphorylation of the NF-κB p65 subunit, which was markedly inhibited by SB203580, a specific inhibitor of p38 MAPK. The inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, significantly ameliorated DOX-induced inflammation, leading to a decrease in the levels of IL-1β and IL-6, as well as TNF-α production in H9c2 cells. The pretreatment of H9c2 cells with either SB203580 or PDTC before exposure to DOX significantly attenuated DOX-induced cytotoxicity. In conclusion, our study provides novel data demonstrating that the p38 MAPK/NF-κB pathway is important in the induction of DOX-induced inflammation and cytotoxicity in H9c2 cardiac myocytes.

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Hyperglycemia is a risk factor for the development of diabetic cardiovascular complications, which are associated with the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. In this study, we demonstrate the inhibitory effects of exogenous hydrogen sulfide (H₂S) on the activation of the MAPK pathway. The aim of the present study was to determine whether exogenous H₂S prevents high glucose (HG)-induced injury by inhibiting the activation of the p38 MAPK and extracellular signal-regulated kinase (ERK)1/2 (members of MAPK) pathways in cardiomyoblasts (H9c2 cells). The findings of the present study demonstrated that the treatment of H9c2 cells with HG (35 mM glucose) for 24 h not only significantly induced injury, including cytotoxicity, apoptosis, overproduction of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential (MMP), but also upregulated the expression levels of phosphorylated (p)-p38 MAPK and p-ERK1/2. The increased expression levels of p-p38 MAPK and p-ERK1/2 were markedly reduced by pre-treatment of the H9c2 cells with 400 µM sodium hydrogen sulfide (NaHS; a donor of H2S) prior to exposure to 35 mM glucose. Importantly, pre-treatment of the cells with 400 µM NaHS or 3 µM SB203580 (a selective inhibitor of p38 MAPK) or 15 µM U0126 (a selective inhibitor of ERK1/2) attenuated the HG-induced cardiomyocyte injury, leading to an increase in cell viability and a decrease in the number of apoptotic cells, preventing ROS generation, as well as the loss of MMP. In addition, pre-treatment of the cells with 1,000 µM N‑acetyl‑L‑cysteine (a ROS scavenger) prior to exposure to HG ameliorated the HG-induced cytotoxicity. Taken together, the data from the present study demonstrate for the first time, to our knowledge, that exogenous H2S exerts a protective effect against HG‑induced injury by inhibiting the activation of the p38 MAPK and ERK1/2 pathways and preventing oxidative stress in H9c2 cells.

Interleukin-12 and interleukin-2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model

Aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. Th1 cytokines could enhance fungicidal activity. The effects from the combination of interleukin‐12 (IL‐12) and IL‐2 are rarely known in invasive pulmonary aspergillosis infection. To assess the cleaning of A. fumigatus infection in the pulmonary tissues by IL‐12 and IL‐2, interferon‐γ (IFN‐γ) was detected in the sera using ELISA, quantification of IFN‐γ mRNA using real‐time RT‐PCR and lung Colony‐forming unit was assayed by cultivation. Morphology was analysed by histopathological examination. Our results showed that IL‐12 and/or IL‐2 could enhance the IFN‐γ expression in the pulmonary tissue, reduce the colony load in the pulmonary tissue and increase the survival rate of mouse. The combination of IL‐12 and IL‐2 could assist in increasing the IFN‐γ expression in the pulmonary tissue, but neither reduce colony load in the pulmonary tissue nor increase the survival rate of mouse significantly. It was demonstrated that IL‐12 and IL‐2 were strong immunomodulatory cytokines as a prerequisite for protecting the host from infectious agents.

Case-Control Study on Impact of the Telomerase Reverse Transcriptase Gene Polymorphism and Additional Single Nucleotide Polymorphism (SNP)- SNP Interaction on Non-Small Cell Lung Cancers Risk in Chinese Han Population.

To investigate the impact of telomerase reverse transcriptase (TERT) gene polymorphism and additional SNP–SNP interaction on non‐small cell lung cancer (NSCLC) risk in Chinese population.

The serum glucan level and pathological changes of antifungal treatment for lower respiratory tract infection of Candida albicans

Due to the fact that Candida albicans colonizes in the upper respiratory tracts of healthy people, whether or not its isolation from airway secretions is sufficient to warrant treatment remains controversial. The animal models of immunosuppressive rats with pulmonary candidiasis were established by the intratracheal inoculating suspensions of C. albicans, and the animals were divided into the following three groups: (1) antifungal treatment group, (2) saline control group, and (3) blank control group. We noted the following in our studies: (1) The fungal load of the saline control group gradually increased such that it was higher than those of the antifungal treated group and was significant from the fourth day of treatment (P < 0.01). (2) The serum (1,3)-β-D-glucan (BG) in the saline control group also gradually increased so that it was significantly higher than found with the treated group by the sixth day of treatment (P < 0.05), and in fact, the rank of pulmonary colony count and BG in the two groups at different time points showed an almost perfect linear correlation. (3) The median survival period of the rats in the antifungal treated group and saline control group was 15 and 8 days respectively, no rats died in the blank control group. (4) The lung lesions from the saline control group gradually became more aggravated than those in the antifungal treated group; no significant pathological changes were found in the blank control group. Antifungal treatment (micafungin) is capable of efficaciously decreasing the lung fungal burden, and continuous monitoring of BG is useful for the evaluation of therapeutic effect of antifungals. Infection of C. albicans with associated pathological damage implies the need for antifungal therapy.

The Establishment of Realtime Fluorescent Quantitative Polymerase chain reaction(PCR) for Detection of Highly Pathogenic Avian Influenza Virus Subtype H5N1

Highly pathogenic strains of avian influenza virus (AIV), which are influenza A viruses, cause severe disease in domestic poultry and humans. The objective of this study was to establish a fluorescent quantitative RT-PCR assay for detection of highly pathogenic avian influenza virus (AIV) subtype H5N1. The H5 and N1 subtypespecific probe sets were developed based on avian influenza virus sequences detected in China. Two pairs of primers and two fluorescent probes were strictly designed and optimized in a reaction system. According to the amount of plasmid RNA extracted from H5N1 strains, the standard curve DWQBGWDWQBGW of fluorescent quantitative PCR was drawn and all of the specimens were then tested by means of Real-time PCR. The test of highly pathogenic AIV subtype H5N1 was identified to be specific and its sensitivity level was 102~103 copies/reaction. The standard curve was accomplished at 109～105 DNA copies/reaction. It took only three hours from viral RNA extraction through to completion of the test. The assay was easy to carry out and highly reproducible. In conclusion, fluorescent quantitative PCR, described here, provides a rapid, specific and sensitive method to detect not only the H5 but N1 genes as well.