Oncosuppressive role of MicroRNA-205-3p in gastric cancer through inhibition of proliferation and induction of senescence: Oncosuppressive role of MicroRNA-205 in gastric cancer.

BACKGROUND: Our previous study showed that CXCL11 could play an immunomodulatory role. In this study, we investigated the regulator (miR-205-3p) of CXCL11 and the mechanism of miR-205-3p as a tumor suppressor gene in gastric cancer (GC). MATERIALS AND METHODS: A target relationship between miR-205-3p and CXCL11 was revealed by using the bioinformatics method. This study detected the expressions of miR-205-3p and CXCL11 through qRT-PCR and Western blotting. Moreover, the expressions of Akt, PD-L1, p16, p21, and senescence-associated secretory phenotype (SASP) factor were determined. The effects of miR-205 on proliferation, invasion, and senescence of GC cells were assessed by using methods, such as transfection, Transwell assay, tablet cloning, flow cytometry, and senescence-associated beta-galactosidase (SA-ß-gal) staining. Furthermore, the effects were verified using methods, like immunohistochemistry, flow cytometry and SA-ß-gal in animal experiments. RESULTS: Based on the study, it is found that the expression of miR-205-3p is down-regulated, while that of CXCL11 is up-regulated in GC cell lines. By regulating CXCL11, miR-205-3p inhibits Akt activation, reduces the proliferation and invasion of GC cells, promotes cell apoptosis, induces senescence of GC cells, and secretes immunostimulatory SASP factor. The animal experiments confirm that miR-205-3p promotes cell senescence, down-regulates the immunosuppressive signal induced by PD-L1, and promotes secretion of immunostimulatory SASP factor, so that more T cells are recruited in blood and tumors. CONCLUSIONS: This study revealed the molecular mechanism of miR-205-3p in inhibiting proliferation and invasion and inducing senescence of GC cells by regulating CXCL11 and Akt pathways in animal and cell experiments.

Exacerbating effects of PM2.5 in OVA-sensitized and challenged mice and the expression of TRPA1 and TRPV1 proteins in lungs.

OBJECTIVE: To investigate the effects of particulate matter ≤ 2.5 microns (PM2.5) on asthma-related phenotypes and on lung expression of TRPA1 and TRPV1 proteins in a mouse model of asthma. METHODS: Female BALB/c mice were utilized to establish 28- and 42-day asthma models. Mice were sensitized with ovalbumin (OVA) and challenged with OVA, OVA plus normal saline (NS), or OVA plus PM2.5 at two doses, 1.6 or 8.0 mg kg-1. PM2.5 was instilled intratracheally without anesthesia. After the final OVA challenge was performed, 24 hours later, the changes in airway resistance (RI) and lung dynamic compliance (Cdyn) in response to acetylcholine chloride (ACH) were evaluated, and blood, bronchoalveolar lavage fluid (BALF) and lung tissue were taken at that time. The number of eosinophils in blood and various leukocytes in BALF were determined. Lung protein was extracted and probed for TRPA1 and TRPV1 expression. Interleukin (IL)-13, substance P (SP), prostaglandin D2 (PGD2) and nerve growth factor (NGF) in BALF were measured by enzyme-linked immunosorbent assay. RESULTS: PM2.5 treated mice showed significantly greater changes in the number of inflammatory cells in blood and BALF, in RI and Cdyn in response to ACH, and in lung histopathology, indicated by inflammatory cell infiltration, thickened bronchial smooth muscles and bronchial mucosa damage, compared to controls. In addition, higher expression of TRPA1 and TRPV1 in lung and IL-13, SP, PGD2 and NGF in BALF were seen in mice exposed to PM2.5. All effects were most pronounced in mice in the 42-day model. CONCLUSIONS: PM2.5 exacerbates effects of asthma in this model, possibly by regulating TRPA1 and TRPV1 and the relevant neurokines.

Radiation enhancing effects of sanazole and gemcitabine in hypoxic breast and cervical cancer cells in vitro.

AIM OF THE STUDY: Sanazole and gemcitabine have been proven clinically as hypoxic cell radiosensitisers. This study was conducted to determine the radiation enhancing effects of sanazole and gemcitabine when administered together at relevant concentrations into hypoxic human MCF-7 and HeLa cells. MATERIAL AND METHODS: A 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Cell surviving fractions were determined by the standard in vitro colony formation assay. RESULTS: The cell colony formation assay indicated that the radiosensitivity of hypoxic MCF-7 and HeLa cells was enhanced by sanazole or gemcitabine. The combination of the two drugs displayed significant radiation enhancing effects at the irradiation doses of 6, 8, and 10 Gy in both cell lines, which were arrested in the S phase. CONCLUSIONS: This study indicated that the co-administration of the two drugs may result in a beneficial gain in radio-therapy for hypoxic breast cancer and cervical cancer.

Radiation enhancing effects with the combination of sanazole and irinotecan in hypoxic HeLa human cervical cancer cell line.

PURPOSE: This study was conducted to determine the synergistic radiation sensitizing effects of the combination of sanazole and irinotecan in hypoxic cervical cancer HeLa human tumor cell line. METHODS: The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Surviving cell fractions were determined by the standard in vitro colony formation assay. RESULTS: The MTT assay showed that the presence of irinotecan with or without sanazole reduced significantly the cells' viability. Flow cytometry demonstrated that the combination of sanazole and irinotecan led to more HeLa cells blocked in G(2) phase. Cell colony formation assay indicated that the radiosensitivity of hypoxic HeLa cells was enhanced by sanazole and/or irinotecan. CONCLUSION: This study showed that the radiation enhancing effects produced by the combination sanazole and irinotecan was significant in hypoxic HeLa cells, which were arrested in the G(2) phase of the cell cycle. This study may provide a new combination modality of radiosensitizers in the radiotherapy of cervical cancer.

Curcumin prevents dopaminergic neuronal death through inhibition of the c-Jun N-terminal kinase pathway.

Recent studies have shown that the c-Jun N-terminal kinase (JNK) signaling pathway is involved in dopaminergic neuronal degeneration, and direct blockade of JNK by specific inhibitors may prevent or effectively slow the progression of Parkinson disease (PD). Previous studies have revealed that the natural phenolic compound curcumin can reduce inflammation and oxidation, which makes it a potential therapeutic agent for neurodegenerative diseases. In this study, we investigated whether curcumin protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) or 1-methyl-4-phenylpyridnium ion- (MPP(+)) induced dopaminergic neurotoxicity in C57BL/6N mice or SH-SY5Y cells by inhibiting JNK pathways both in vivo and in vitro. Curcumin treatment significantly improved behavioral deficits, and enhanced the survival of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) in the MPTP-induced PD model mice. Most importantly, curcumin treatment significantly inhibited MPTP/MPP(+)-induced phosphorylation of JNK1/2 and c-Jun, and cleaved caspase-3. Our study suggests that the neuroprotective effect of curcumin is not related simply to its antiinflammatory and antioxidant properties, but involves other mechanisms, particularly by targeting the JNK pathways.

[Correlation between immunochemical level and patient with caries].

OBJECTIVE: To explore the relationship between immunochemical level of salivary and caries in children aged 4-6 years old. METHODS: Two groups were assorted as patients with caries and without caries. Every group included 45 people. Measurements of salivary secretory immunoglobulin A (SIgA)were performed by using radio-immunoassay and single agar diffusion assay. The levels of lysozyme (LZ), alkaline phosphatase (ALP) and lactic dehydrogenase (LDH) were studied with colorimetry and turbidimentry. RESULTS: The levels of LDH, SigA, ALP, LZ had significant difference between the two groups (P < 0.05). The level of LDH between patients and peoples without caries had little difference (P > 0.05). CONCLUSION: The incidence of caries is associated with age, and it may have association with immunochemical levels of salivary.