siRNA-mediated inhibition of HBV replication and expression

AIM: RNA interference (RNAi) is a newly discovered phenomenon provoked by dsRNA. The dsRNA is initially cleaved by Dicer into 21-23 nt small interfering RNA (siRNA) and can then specifically target homologous mRNA for degradation by cellular ribonucleases. RNAi has been successfully utilized to down-regulate the endogenous gene expression or suppress the replication of various pathogens in mammalian cells. In this study, we investigated whether vector-based siRNA promoted by U6 (pSilencer1.0-U6) could efficiently inhibit HBV replication in cell culture.METHODS: pSilencer vectors with inserts targeting on different regions of HBV genome were constructed. These plasmids were co-transfected with pHBV3.8 into Huh-7 cells via lipofection and viral antigens were measured by ELISA. Viral RNA was analyzed by Northern blot. The mRNA of MxA and 2'-5'OAS was reverse transcribed and quantified by real-time PCR.RESULTS: Vector-based siRNA could potently reduce hepatitis B virus antigen expression in transient replicative cell culture. Furthermore, Northern blot analysis showed that viral RNA was effectively degraded, thus eliminating the messengers for protein expression as well as template for reverse transcription. Real-time PCR analysis of cellular MxA and 2'-5'OAS gene expression revealed that vector-based siRNA did not provoke the interferon pathway which reassured the specificity of the vector-based RNA interference technique.CONCLUSION: Our results indicate that RNA interference may be a potential tool to control HBV infection.</p

microRNA-33a-5p increases radiosensitivity by inhibiting glycolysis in melanoma.

Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis. In contrast, cell proliferation was upregulated after inhibition of miR-33a-5p in WM35 cells, accompanied by increased glycolysis. Overexpression of miR-33a-5p enhanced the sensitivity of melanoma cells to X-radiation by MTT assay, while downregulation of miR-33a-5p had the opposite effects. Finally, in vivo experiments with xenografts in nude mice confirmed that high expression of miR-33a-5p in tumor cells increased radiosensitivity via inhibiting glycolysis. In conclusions, miR-33a-5p promotes radiosensitivity by negatively regulating glycolysis in melanoma

Estrogen Inhibits Colon Polyp Formation by Reducing Angiogenesis in a Carcinogen-Induced Rat Model

Objective. To study the effects of estrogen on colon polyp formation, proliferation, and angiogenesis on a rat model of colon cancer induced by dimethylhydrazine (DMH). Methods. Thirty-six female ovariectomized (OVX) rats were randomly divided into 3 groups: (I) control group (administrated with vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH + E2 group (administrated with DMH and 17β-estradiol weekly). The incidence, volumes, and multiplicity of colon polyps in each group were evaluated. The microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen (PCNA), and the expressions of HIF-1α and VEGF in polyps were detected in each group. Results. Estrogen reduced the multiplicity, volumes, and the PCNA expressions of DMH-induced colon polyps. The MVD in DMH + E2 group was significantly lower than that in DMH group. Estrogen treatment decreased the HIF-1α and VEGF expressions at both mRNA and protein level. Conclusion. Estrogen replacement was protective for ovariectomized rats from DMH-induced carcinogenesis, and one of the mechanisms for this was due to estrogen’s inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1α expressions

Tourmaline composition probes serpentinite-derived fluid mobility in subduction zones

Serpentinite dehydration in subduction zones plays a pivotal role in geochemical cycling on Earth. A number of geochemical studies on arc magmas have elucidated the contributions of serpentinite-derived fluids to mantle sources. However, due to complex geological overprints during subduction zone processes, discerning serpentinite signatures in exposed metamorphic rocks within fossil subduction zones remains challenging. In this study we address these difficulties through in-situ investigations of tourmaline, the geochemistry of which reflects the host environment as well as potential fluid-induced processes. The presence of zonations in tourmaline makes it an excellent recorder of consecutive geological events. Integrated major and trace elements along with in-situ boron isotopes of tourmaline from the high-pressure Sopron area (Hungary) in the Eastern Alps were used to unravel fluid action sourced from serpentinite. Despite the presence of color zoning, tourmaline in the orthogneiss (Tur-G) has low XMg [Mg/(Mg + Fe)] of ca. 0.3–0.6 and δ11B values of around −11 ‰, along with variable trace element compositions. Petrological observations and geochemical analyses suggest that the inner domains of Tur-G are of igneous origin, while the outer rims are likely affected by subsequent metamorphic events. Tourmaline in metasomatized kyanite-quartzite (Tur-K) veins exhibits distinct geochemical zoning, and preserves metamorphic cores and fluid-induced rims. The inner domains of Tur-K display low XMg (&lt;0.6), relatively high trace element concentrations and δ11B values of less than −10 ‰, whereas the overgrowths exhibit extremely high XMg values (&gt;0.99), low trace element concentrations and high δ11B values reaching up to +21 ‰, clearly indicating the incorporation of serpentinite-derived Mg-11B-rich fluids. Through comparison with other metamorphic and metasomatic tourmalines in (ultra)high-pressure rocks globally, we establish that tourmaline with high XMg &gt; 0.85 and δ11B values &gt;0 ‰ may serve as an effective proxy for detecting serpentinite-derived fluids in subduction zones

Sports promote brain evolution: a resting-state fMRI study of volleyball athlete

BackgroundLong-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear.MethodWe conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups.ResultsNo significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group.ConclusionThis study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registrationRegistration number: ChiCTR2400079602. Date of Registration: January 8, 2024