Dihydroartemisinin Affects STAT3/DDA1 Signaling Pathway and Reverses Breast Cancer Resistance to Cisplatin.

Dihydroartemisinin (DHA) has anticancer effects on multiple tumors, including those associated with breast cancer. This study aimed to investigate the mechanism causing DHA-reversing cisplatin (DDP) resistance in breast cancer. Relative mRNA and protein levels were tested using a qRT-PCR and western blot assay. Cell proliferation, viability, and apoptosis were evaluated using colony formation, MTT, and flow cytometry assays, respectively. Interaction of STAT3 and DDA1 was measured via a dual-luciferase reporter assay. The results showed that DDA1 and p-STAT3 levels were dramatically elevated in DDP-resistant cells. DHA treatment repressed proliferation and induced apoptosis of DDP-resistant cells by suppressing STAT3 phosphorylation; the inhibition ability was positively proportional to the DHA concentration. DDA1 knockdown inhibited cyclin expression, promoted G0/G1 phase arrest, restrained cell proliferation, and induced apoptosis of DDP-resistant cells. Furthermore, knockdown of STAT3 restrained proliferation and induced apoptosis and G0/G1 cell cycle arrest of DDP-resistant cells by targeting DDA1. DHA could restrain tumor proliferation of breast cancer via enhancing drug sensitivity of DDP-resistant cells through the STAT3/DDA1 signaling pathway.

Nobiletin promotes the pyroptosis of breast cancer via regulation of miR-200b/JAZF1 axis.

Nobiletin is a polymethoxylated flavone present in citrus fruits, which has been reported to have inhibitory effects on tumorigenesis of cancers. However, the biological function of nobiletin in breast cancer (BC) is largely unknown. To investigate the effect of nobiletin on growth of BC cells, the cell viability of BC was measured by MTT assay. In addition, gene and protein expressions were detected by qRT-PCR and western blot, respectively. The apoptosis and pyroptosis of BC cells were tested by flow cytometry. Finally, the correlation between miR-200b and JAZF1 was detected by dual luciferase report. The data indicated that nobiletin inhibited the proliferation of BC cells in a dose-dependent manner. Moreover, miR-200b mimics-induced pyroptosis of BC cells was further increased by nobiletin. Meanwhile, JAZF1 was found to be the target of miR-200b. Moreover, nobiletin induced apoptosis and pyroptosis of BC cells via miR-200b/JAZF1/NF-κB axis. In conclusion, nobiletin inhibited the tumorigenesis of BC via regulation of miR-200b/JAZF1 axis. Thus, nobiletin might serve as a new agent for the treatment of BC.

Stripe and supersolid phases of spin-orbit coupled spin-2 Bose-Einstein condensates in an optical lattice.

We study the ground-state phases of two-dimensional spin-orbit coupled spin-2 Bose-Einstein condensates in a one-dimensional spin-dependent optical lattice. Due to the competition among optical lattice, spin-orbit coupling and spin-exchange interaction, the exotic ground-state phases are found, i.e. three types of the stripe phases and three types of the supersolid phases. The spin-exchange interaction can adjust the direction of the stripe in the stripe phase and generate various vortex lattice structures in the supersolid phase, which shows that the spin-exchange interaction plays an important role in the formation of the stripe and supersolid phases of spin-orbit coupled spin-2 Bose-Einstein condensates in an optical lattice.

Ground-state phases of spin-orbit coupled spin-1 Bose-Einstein condensate in a plane quadrupole field.

We study the ground-state phases of two-dimensional spin-orbit coupled spin-1 Bose-Einstein condensate loaded in a plane quadrupole field. In the absence of rotation, for the fixed spin-orbit coupling strength, the ordinary stripe phase is found when the strength of the magnetic field gradient is small. As the strength of magnetic field gradient enhances, the system realizes the phases with three layer vortices along the radial direction. The number of vortices in the second layer is successively increased and the vortices in the outermost layer disappear when the strength of magnetic field gradient surpass the critical value. For the large strength of magnetic field gradient, the system only has the inner layer vortices. The magnetic field inhibits the region of vortices. For the fixed magnetic field gradient strength, the vortices of the system elongate along the radial direction and form a series of vortex lines, the number of the vortex line increases as the strength of spin-orbit coupling enhances. By adding the rotation, for the fixed strengths of spin-orbit coupling and magnetic field gradient, the number of second layer vortices also successively increases as the rotational frequency increases. The number of vortices in the certain layer of the ground-state density can be regularly changed under the effects of the magnetic field and spin-orbit coupling.

Resveratrol inhibits interleukin 1ß-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity.

In chondrocytes, resveratrol, a natural SIRT1 activator, exerts an anti-inflammatory response via inhibition of nuclear factor kappaB (NF-κB). Given that SIRT1 inhibits the transactivation potential of NF-κB by deacetylating acetylated lysines in p65, the NF-κB subunit, we investigated the effects of resveratrol-activated SIRT1 on articular chondrocytes. We found that when chondrocytes were stimulated with interleukin 1ß (IL-1ß), the time- and dose-dependent expression of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was suppressed by resveratrol. Resveratrol-activated SIRT1 mediated this suppression. SIRT1 suppressed not only the nuclear translocation of NF-κB but also the acetylation of p65. Furthermore, acetylated Lys310 in p65, which must be present for transactivation activity, was the immediate downstream target of SIRT1. Therefore, SIRT1 protects against the inflammatory response induced by IL-1ß in articular chondrocytes. Resveratrol, as an activator of SIRT1, merits consideration as a therapeutic agent in the treatment and prevention of osteoarthritis.

Endoplasmic reticulum stress induced by tunicamycin and antagonistic effect of Tiantai No.1 (1) on mesenchymal stem cells.

OBJECTIVE: Changes of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum (ER). This ER function disorder is called endoplasmic reticulum stress (ERS). Severe long-term ERS can trigger the ER apoptosis signaling pathway, resulting in cell apoptosis and organism injury. Recent researches revealed that ERS-induced cell death was involved in the neurocyte retrogradation in the progress of neuron degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and so on. Therefore, the protection effect of the traditional Chinese drug-Tiantai No. 1 (1) on the ERS injury of AD was investigated at the molecular gene level in this study with a view to explore the gene pharmacodynamic actions and mechanisms of this drug. METHODS: Primarily cultured marrow mesenchymal stem cells (MSCs) of rats were treated by tunicamycin (TM) in order to induce ERS. RT-PCR, fluorescence immunocytochemistry and Western blot techniques were used to determine the mRNA and protein expression levels of the protective stress protein-ER molecular chaperones GRP78 and GRP94 (which would assist cells to resist cellular stress injury), and to determine the mRNA and protein expression levels of apoptosis promoting molecule Caspase-12 on the membrane of the ER, respectively. RESULTS: Protein expression levels of GRP78 and GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of Caspase-12 was also remarkably increased in the TM-induced MSCs (P<0.05). All these proved that the ERS model was successfully established by TM in MSC. Meanwhile, the mRNA and protein levels of GRP78 and GRP94 were all significantly increased compared with the model group (P<0.05 or P<0.01) after MSCs were treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase-12 were significantly decreased compared with the model group (P<0.05 or P<0.01). This effect showed a dose dependent manner. CONCLUSION: Tiantai No.1 might attenuate the cell apoptosis induced by ERS injury, and thus protect the neurons against AD.

Diagnostic model of saliva protein finger print analysis of patients with gastric cancer.

AIM: To explore the method for early diagnosis of gastric cancer by screening the expression spectrum of saliva protein in gastric cancer patients using mass spectrometry for proteomics. METHODS: Proportional peptide mass fingerprints were obtained by analysis based on proteomics matrix-assisted laser desorption ionization time-of-flight/mass spectrometry. A diagnosis model was established using weak cation exchange magnetic beads to test saliva specimens from gastric cancer patients and healthy subjects. RESULTS: Significant differences were observed in the mass to charge ratio (m/z) peaks of four proteins (1472.78 Da, 2936.49 Da, 6556.81 Da and 7081.17 Da) between gastric cancer patients and healthy subjects. CONCLUSION: The finger print mass spectrum of saliva protein in patients with gastric cancer can be established using gastric cancer proteomics. A diagnostic model for distinguishing protein expression mass spectra of gastric cancer from non-gastric-cancer saliva can be established according to the different expression of proteins 1472.78 Da, 2936.49 Da, 6556.81 Da and 7081.17 Da. The method for early diagnosis of gastric cancer is of certain value for screening special biological markers.