Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24.

Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model.

Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model.

The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.

ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity.

Characteristics of participants' and caregivers' influence on non-response in a cross-sectional study of dementia in an older population.

Objective: The issue of non-response in dementia epidemiological studies, which may result in the underestimation of the prevalence of dementia, has attracted little attention. We aimed to explore the causes and related factors of non-response in a dementia survey among Chinese veterans.

Methods: A two-phase, cross-sectional study investigated the prevalence of dementia and mild cognitive impairment in Chinese veterans aged ≥ 60 years.

Veratric Acid Inhibits LPS-Induced IL-6 and IL-8 Production in Human Gingival Fibroblasts.

Veratric acid, one of the major benzoic acid isolated from vegetables and fruits, has been reported to have anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of veratric acid on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). HGFs were pretreated with veratric acid 1 h before LPS stimulation.

Synthesis and antibacterial activity of naphthyridone derivatives containing mono/difluoro-methyloxime pyrrolidine scaffolds.

A series of novel naphthyridone derivatives containing mono/difluoro-methyloxime pyrrolidine scaffolds were designed and synthesized. These derivatives were initially evaluated for their in vitro antibacterial activity and compounds 13a1, b1 were chosen for further evaluation their in vivo activity against systemic infections in mice. The results indicate that all of the target compounds have considerable in vitro antibacterial activity.

HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a cancer targeting gene-viro-therapy strategy.

Background: In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an adenovirus has been frequently utilized to regulate the cancer cell specificity of a virus.

Synthesis and in vitro antibacterial activity of a series of novel gatifloxacin derivatives.

A series of novel gatifloxacin (GTFX) derivatives were designed, synthesized and characterized by (1)H NMR, (13)C NMR, MS and HRMS. These derivatives were evaluated for in vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Our results reveal that most of the target compounds show good potency in inhibiting the growth of Staphylococcus aureus including MRSA and Staphylococcus epidermidis including MRSE.

Synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones.

To explore new agents of quinolone derivatives with high antibacterial activity, 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones were designed and synthesized, and their activity against gram-positive and gram-negative strains was tested in vitro. Sixteen target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis.

[Synthesis and antibacterial activity of 7-(3-amino-4-alkoxyimino-1 -piperidyl) -quinolones].

To explore new agents of quinolone derivatives with high activity against Gram-positive and Gram-negative microorganisms, 7-(3-amino-4-alkoxyimino-1-piperidyl) quinolones were designed and synthesized, and their activity against Gram-positive and Gram- negative microorganisms were tested in vivo and in vitro. Twenty one target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis.

[Security of dual cancer-specific targeting vector and its cytotoxic effect when harbored].

Background & Objective: The xenograft tumor mass in nude mice could be completely eliminated using the targeting dual gene-virotherapy strategy. Now, the most important point is to improve its security. This study was to construct dual cancer-specific targeting adenovirus called TD55 to evaluate its security, and construct TD55-TRAIL to explore its antitumor effect.

Impairment of redox state and dopamine level induced by alpha-synuclein aggregation and the prevention effect of hsp70.

One hypothesis for the etiology of Parkinson's disease (PD) is that the formation of proteinaceous inclusion, which is mainly composed of alpha-synuclein, may contribute to the selective loss of dopaminergic neurons. To further explore the role of alpha-synuclein in neurodegeneration of PD, we examined the possible effects of aggregated alpha-synuclein on the intracellular redox state, dopamine level, and cell death of SK-N-SH cells. Our present studies show that alpha-synuclein aggregation gives rise to both elevated intracellular oxidative state and dopamine level in SK-N-SH cells.

[Synthesis and antibacterial activity of 7-(7-aminomethyl-5-azaspiro [2,4] hept-5-yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its analogues].

Aim: To find new antibacterial agents of quinolone with high activity and low toxicity.

Methods: To design and synthesize 7-(7-aminomethyl-5-azaspiro [2,4] hept-5-yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its analogues, and to study their antibacterial activity in vitro and in vivo.

Results: Twenty new compounds (2 - 11, 17 - 26) were obtained including five targeted compounds (22 - 26).

An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy.

ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone. In this paper, we put forward a novel concept of Gene-ViroTherapy strategy and in this way, we constructed an armed therapeutic oncolytic adenovirus system, ZD55-gene, which is not only deleted of E1B 55-kD gene similar to ONYX-015, but also armed with foreign antitumor gene.

Expression of Brain-derived Neurotrophic Factor (BDNF) Gene in Rat Myoblast Cells.

Brain-derived neurotrophic factor (BDNF) gene was cloned into retrovirous vector plasmid pLNCX to form the pLNC/BDNF. After packaging in PA317 cell line, the infectious particles were used to infect rat myoblast cell line L-6TG. After selection with G418, the L-6TG/BDNF cells were collected.

Cloning of Glial Cell Line-derived Neurotrophic Factor Gene and Its Expression in Eukaryotic Cells.

Glial cell line-derived neurotrophic factor gene (gdnf) was obtained by RT-PCR method. Its pro-duct in COS7 cells showed neurotrophic and protective effect on the dopaminergic neurons. Then gdnf gene was cloned into retrovirus vector pLNCX and packaged with PA317.

A Novel Type of Apoptosis Induced by Cadmium in BA/F3beta Cells.

Apoptosis is usually accompanied by DNA fragmentation and up-regulation of reactive oxygen species, and it can be inhibited by overexpression of Bcl-2. Here, cadmium was found to induce apoptosis in BA/F3beta cells. MTT assay, Hochest 33258 staining, and transmission electron microscopy analysis were used to detect the apoptosis, however, neither DNA fragmentation nor up-regulation of reactive oxygen species were observed in this type of apoptosis.

Ubiquitin Conjugating Enzyme Ubc9 is Involved in Protein Degradation of Redox Factor-1 (Ref-1).

Redox factor-1 (Ref-1) is a bifunctional protein playing an important role in both cellular redox regulation and DNA apurinic/apyrimidinic sites' repair. To find Ref-1interacting proteins (Rips), a yeast two-hybrid screening was performed by using Ref-1 redox domain as the 'bait', and five positive clones were obtained. One of them (Rip3) was identified to be the ubiquitin-conjugating enzyme Ubc9.

Interaction between Jak3 and Nucleosome Assembly Protein 1.

Tyrosine kinase Jak3 plays a critical role in the interleukin 2 IL-2 signaling because it not only participates the Jak-Stat pathway, but also interacts with unidentified signal transducers and regulates expression of some oncogenes such as c-fos and c-myc. Abundant evidence demonstrated that phosphorylated tyrosine was necessary for the interaction between two proteins. Therefore, in order to clarify the role of Jak3 in IL-2 signal transduction, the tyrosine-phosphorylation-involved yeast two-hybrid system was constructed and the N-terminal region JH3-JH7 of Jak3 was used as a bait to screen a peripheral blood cDNA library.

Interleukin-2 gene has superior antinociceptive effects when delivered intrathecally.

The antinociceptive effect of interleukin-2 gene on rat carrageenan-induced pain was explored using different delivery methods. Intrathecal (i.t.

Blocking HSF1 by dominant-negative mutant to sensitize tumor cells to hyperthermia.

Heat shock protein 70 (HSP70), an antiapoptotic chaperon protein, is highly expressed in human breast tumors and renders them resistant to such therapy as hyperthermia. In the present study, we inhibited the expression of HSP70 by blocking the heat shock transcription factor 1 (HSF1) function with its dominant-negative mutant (mHSF1) in Bcap37 cells, a thermotolerant breast cancer cell line. Here we report that retrovirus-mediated transfer of mHSF1 led to massive cell death of Bcap37 after hyperthermia.