MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20.

Although the oncogenic roles of regulator of G protein signaling 20 (RGS20) and its upstream microRNAs (miRNAs) have been reported, their involvement in hepatocellular carcinoma (HCC) remains unexplored. We utilized the starBase, miRDB, TargetScan, and mirDIP databases, along with a dual-luciferase reporter assay and cDNA chip analysis to identify miRNAs targeting RGS20. miR-204-5p was selected for further experiments to confirm its direct targeting and downregulation of the RGS20 expression. To study the miR-204-5p/RGS20 axis in HCC, RGS20 and miR-204-5p were increased in PLC/PRF/5/Hep3B cells, and the viability, hyperplasia, apoptosis, cell cycle, and invasion/migration of the cells were assessed. RGS20 exhibited optimism, while miR-204-5p exhibited pessimism in tumors. miR-204-5p directly targeted RGS20 and downregulated its expression, whereas high RGS20 expression indicated a poor prognosis. Transfection of miR-204-5p inhibited the hyperplasia, migration, and invasion of HCC cells, but promoted apoptosis and influenced the levels of cyclin-dependent kinase 2 (CDK2), cyclin E1, B-cell lymphoma-2 (Bcl-2), Bax, and cleaved caspase-3/8. These effects were reversed by overexpression of RGS20. We recognized miR-204-5p as an upstream regulator targeting RGS20, thereby inhibiting HCC progression by downregulating RGS20 expression. RGS20 may prove to be a potential target for HCC treatment, and miR-204-5p might seem like to be a potential miRNA in gene therapy.

Babao Dan alleviates gut immune and microbiota disorders while impacting the TLR4/MyD88/NF-кB pathway to attenuate 5-Fluorouracil-induced intestinal injury.

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1ß, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.

ANRIL promotes the regulation of colorectal cancer on lymphatic endothelial cells via VEGF-C and is the key target for Pien Tze Huang to inhibit cancer metastasis.

lncRNA ANRIL is an oncogene, however the role of ANRIL in the regulation of colorectal cancer on human lymphatic endothelial cells (HLECs) is remain elusive. Pien Tze Huang (PZH, PTH) a Tradition Chinese Medicine (TCM) as an adjunctive medication could inhibit the cancer metastasis, however the mechanism still uncovering. We used network pharmacology, subcutaneous and orthotopic transplanted colorectal tumors models to determine the effect of PZH on tumor metastasis. Differential expressions of ANRIL in colorectal cancer cells, and stimulating the regulation of cancer cells on HLECs by culturing HLECs with cancer cells' supernatants. Network pharmacology, transcriptomics, and rescue experiments were carried out to verify key targets of PZH. We found PZH interfered with 32.2% of disease genes and 76.7% of pathways, and inhibited the growth of colorectal tumors, liver metastasis, and the expression of ANRIL. The overexpression of ANRIL promoted the regulation of cancer cells on HLECs, leading to lymphangiogenesis, via upregulated VEGF-C secretion, and alleviated the effect of PZH on inhibiting the regulation of cancer cells on HLECs. Transcriptomic, network pharmacology and rescue experiments show that PI3K/AKT pathway is the most important pathway for PZH to affect tumor metastasis via ANRIL. In conclusion, PZH inhibits the regulation of colorectal cancer on HLECs to alleviate tumor lymphangiogenesis and metastasis by downregulating ANRIL dependent PI3K/AKT/VEGF-C pathway.

Thermal poling of multi-wire array optical fiber.

We demonstrate in this paper thermal poling of multi-wire array fibers, which extends poling of fibers with two anodes to ~50 and ~500 wire array anodes. The second harmonic microscopy observations show that second order nonlinearity (SON) layers are developed surrounding all the rings of wires in the ~50 anode array fiber with poling of 1.8kV, 250°C and 30min duration, and the outer rings of the ~500 anode array fiber at lower poling temperature. Our simulations based on a two-dimensional charge dynamics model confirm this can be explained by the self-adjustment mechanism, and show the SON layers are induced from the outer rings to the inner rings.

Simulating the space-charge field formation in thermally poled optical fibers: a new two-rate model for hydrogenated cations.

In thermally poled optical fibers, the second-order nonlinearity has been observed to be distributed in a narrow layer more than 10 µm beneath the anode surface, a result that cannot be explained by current models. In this Letter, we propose a new model based on slow migration of H3O+ and fast H+ migration related to the H3O+ concentration. The numerical simulation results show a narrow layer-shaped distribution of the induced second-order nonlinearity, which retains its magnitude and distribution profile in the migration process, and is in good agreement with the experimental observations.

Investigating the effectiveness of thermally poling optical fibers with various internal electrode configurations.

Twin-hole fibers were thermally poled with different internal electrode configurations, including having only one anode wire in the hole, two anode wires in the two holes, one cathode wire, and two cathode wires in the holes, in comparison to the conventional one anode wire and one cathode wire combination. Second harmonic microscopy was utilized to visually reveal the spatial distribution and to measure the magnitude of the induced second-order optical nonlinearity within the poled fibers. It was found that both one- and two-anode configurations resulted in strong nonlinearity comparable with the conventional case but the two-anode configuration was more reproducible than the one-anode case; for the one-cathode-wire and two-cathode-wire configuration, strong nonlinearity in a ring shape concentric with the fiber outer surface was induced as if the cathode metal wire were in the center of the twin-hole fiber rather than substantially offset. These new results provide strong support for the proposed model of a "self-adjustment" mechanism and point the way to simplified and more repeatable experimental techniques.

Creating second-order nonlinearity in pure synthetic silica optical fibers by thermal poling.

A twin-hole optical fiber with pure synthetic silicate glass between the two electrode holes was thermally poled. The induced second-order nonlinearity (SON) was located at the core-cladding interface sections that were nearly parallel to the poling electric field. The polarization dependence of the induced SON suggests that nonlinearity was due to the presence of a space-charge field, which was probably formed by electron migration among the defects located at the core-cladding interface. The magnitude of the induced SON was measured to be approximately 0.06 pm /V.

Overcoming the impeding effect of core-cladding interface on the progression of the second-order nonlinearity in thermally poled optical fibers.

The spatial distribution of the second-order optical nonlinearity in thermally poled optical fibers was characterized with second-harmonic microscopy. The second-order optical nonlinearity (SON) was found to be distributed in a layer, the progression of which was impeded at the core-cladding interface, which acted as an extra potential barrier to the migrating ions. At higher poling voltages and temperatures, the SON layer could overcome this barrier and extend further into the fiber core. The polarization dependence of the optical nonlinearity within the fiber core was also checked and found to be almost negligible.

Characterization of a second-order nonlinear layer profile in thermally poled optical fibers with second-harmonic microscopy.

Second-harmonic microscopy has been successfully applied to characterize the second-order nonlinear layer in optical fibers thermally poled at 280 degrees C and 3.5 kV for 30 min. The nonlinear layer was found to be approximately 5.1 microm deep under the anode and was not always centered about the closest point between the electrodes.

Investigation of the spatial distribution of second-order nonlinearity in thermally poled optical fibers.

The spatial distribution of second-order nonlinearity in thermally poled optical fibers was characterized by second-harmonic microscopy. The second-order nonlinearity was found to be confined to a thin layer close to the anode surface and progressed further into the silica as the poling time increased. Position uncertainty of the anode metal wire was observed to have an effect, as the nonlinear layers were found not always symmetrically located around the nearest points between the anode and cathode. Optical microscopy results were obtained on etched poled fiber cross-sections and compared with those from second-harmonic microscopy.

Long-period-grating-assisted optical add-drop filter based on mismatched twin-core photosensitive-cladding fiber.

A noninterferometric optical fiber add-drop channel filter based on a mismatched twin-core photosensitive-cladding fiber and long-period fiber grating is demonstrated. With assistance from the fiber grating, co-directional spectrally selective cross coupling between the two cores can be realized with an efficiency of 90%.

Characterization of surface crystallization in Ge-doped graded-index silica glass.

Surface crystallization was induced in Ge-doped silica glass samples from a graded-index optical fiber preform by re-heating them at 1100 degrees C for several hours. X-ray diffraction and second-harmonic generation (SHG) microscopy have been utilized to investigate the crystalline phases formed. Experimental results indicate that the predominant crystalline phase is alpha-cristobalite. The cross-sectional distribution of the crystal particles has also been measured with the SHG microscopy and the result is in good agreement with that from traditional bright field light microscopy.

Viewing structural inhomogeneities at the core-cladding interface of re-heated MCVD optical fiber performs with optical microscopy.

Optical microscopy has been used to observe structural inhomogeneities at the core-cladding interface of re-heated MCVD optical fiber preforms. Experimental results show that the heat treatment has enhanced these core-cladding interface inhomogeneities. Their formation mechanism and effects on optical applications are also discussed.