Hypoxia inducible factor-3α promotes osteosarcoma progression by activating KDM3A-mediated demethylation of SOX9.

Hypoxia/oxygen-sensing signally is closely associated with many tumor progressions, including osteosarcoma (OS). Previous research principally focused on the function of hypoxia-inducible factor (HIF)-1α and HIF-2α as the major hypoxia-associated transcription factors in OS, however, the role of HIF-3α has not been investigated. Our study found that HIF-3α was upregulated in OS tissues and cell lines. HIF-3α overexpression facilitated cell proliferation and invasion, and inhibited apoptosis, whereas HIF-3α knockdown showed the opposite results. Chromatin immunoprecipitation analysis revealed that lysine demethylase 3A (KDM3A) expression was transcriptionally activated by HIF-3α under hypoxia, and KDM3A occupied the SRY-box transcription factor 9 (SOX9) gene promoter region through H3 lysine 9 dimethylation (H3K9me2). Additionally, rescue results revealed that KDM3A or SOX9 overexpression reversed the effects of HIF-3α silence on cell functions. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway inhibitor cucurbitacin I suppressed the promotive effects of HIF-3α overexpression on cell proliferation, invasion and TAK2/STAT3 pathway. Finally, OS cell line MG-63 transfected with HIF-3α short hairpin RNA (HIF-3α shRNA) were subcutaneously injected into nude mice, and the results found that HIF-3α knockdown significantly inhibited the xenograft tumor growth of OS in vivo. In conclusion, this study reveals that HIF-3α promotes OS progression in vitro and in vivo by activating KDM3A-mediated SOX9 promoter demethylation, which may provide a potential therapeutic mechanism for OS.

Bi8Se7: Delocalized Interlayer π-Bond Interactions Enhancing Carrier Mobility and Thermoelectric Performance near Room Temperature.

Environmental heat-to-electric energy conversion provides a promising solution to power sensors used for wearable and portable devices. Yet the near-room-temperature thermoelectric materials are extremely rare. The natural heterostructure [Bi2]m[Bi2Q3]n family provides an important platform to search and develop the cheaper and less toxic of such materials. However, the bottleneck problem in this family is how to enhance the interlayer electrical conductivity (σ). Herein, we uncover for the first time that the delocalized π-bond interaction between the stacking layers in the [Bi2]m[Bi2Se3]n family effectively increases the interlayer carrier mobility (µH) and σ. Moreover, we propose an empirical index, F = Dpx,py(Bi0)/Dpx,py(Bi3+) along the kz direction in the Brillouin zone to evaluate the strength of the interlayer delocalized π-bond. F is optimized at a value of 1, under which µH is maximized. Interestingly, Bi8Se7 possessing an optimal F = 1.06 is predicted to have the best µH in the [Bi2]m[Bi2Q3]n family. Our subsequent experiments confirm the as-synthesized Bi8Se7 exhibiting n-type behavior with a µH value (33.08 cm2/(V s) at 300 K) that is higher than that of BiSe (26.19 cm2/(V s) at 300 K) and an enhanced σ value. Furthermore, the Te/Sb codoping, via varying the top of the valence band, significantly increases the Seebeck coefficient and eventually enhances the ZT value to ∼0.7 in Bi5.6Sb2.4Se5Te2 at 425 K along the hot-pressing direction, which is comparable to the optimized value of BiSe. According to the single parabolic band model prediction, the ZT of Bi5.6Sb2.4Se5Te2 may reach ∼1.2 at 425 K, suggesting a novel and promising n-type thermoelectric material near room temperature.

microRNA-544 promoted human osteosarcoma cell proliferation by downregulating AXIN2 expression.

microRNAs (miRNAs) perform various oncogenic or tumor suppressor functions in carcinogenesis. Currently, the underlying mechanisms of miRNAs in osteosarcoma (OS) are poorly understood. In the present study, it is demonstrated that expression of miR-544 was markedly upregulated in OS cells and clinical tissues. Furthermore, overexpression of miR-544 enhanced OS cell proliferation in vitro. Bioinformatics analysis indicated that miR-544 may target the 3'-untranslated region of axis formation inhibitor 2, which was validated using luciferase reporter gene assays. The present study demonstrated a vital role for miR-544 in promoting OS cell proliferation, indicating that it may represent a novel prognostic factor or therapeutic target for OS.

Effects of gene­activated matrix on autograft healing of anterior cruciate ligament.

The aim of the present study was to observe the effects of gene­activated matrix (GAM) on autograft healing of the anterior cruciate ligament. Forty­eight rabbits were randomly divided into groups A and B. Rabbits were used to construct models of anterior cruciate ligament reconstruction. In group A, transforming growth factor (TGF)­ß1 was locally injected into the bone tunnel, while in group B, empty vector was administered. Tendons were removed to observe histology and ultrastructure and to evaluate biomechanics at postoperative months 1, 3 and 6. Optical microscopy revealed increased numbers of fibroblasts and collagen fibers in group A at each time­point compared with B. Electron microscopy identified increased mitosis and abundance of fibroblasts, endoplasmic reticulum and mitochondria in group A at each time­point compared with B. No significant difference was identified in the biomechanical parameters between the 2 groups at postoperative month 1. At postoperative months 3 and 6, maximum force and elastic modulus were greater in group A compared with group B (P<0.0.5). No significant differences in other biochemical parameters were observed at these time­points. The healing ligament graft transfected with TGF­ß1 by GAM was observed to have improved tissue structure and biomechanical characteristics. The results of the current study may provide a theoretical basis for GAM application in ligament repair.

[An analysis of pharyngeal respiratory pressure before and after onset of obstruction in respiratory obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To study the characteristics of pharyngeal respiratory pressure before and after onset of airflow obstruction events in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The respiratory pressure in nasopharynx, oropharynx, and hypopharynx in 8 patients with OSAHS and 9 normal persons were evaluated through catheter manometer. Base on mean respiratory pressure and the ratio of negative respiratory pressure persistent time, the characteristics of pharyngeal respiratory pressure before and after the event onset were analyzed. RESULTS: During sleep, the pharyngeal respiratory pressure in normal persons had similar and periodical wave shape. The ratio of negative respiratory pressure persistent time was less than 0.5. In patients with OSAHS, when the obstruction of airflow happened, the pharyngeal respiratory pressure fluctuated violently, the wave shape became irregular, and the negative expiratory pressure was evident. The mean respiratory pressure was 1 to 2 order of magnitude larger than in normal persons, even reaching -990 Pa. The ratio of persistent negative pressure time was larger than normal. During the intermittent period, the wave shape of pharyngeal respiratory pressure was regular and periodical, the pressure wave shape was different from onset of obstruction. However, in the intermittent period, the mean respiratory pressure, the ratio of negative respiratory pressure persistent time, and other characteristics were still statistically different from normal persons (P < 0.05). CONCLUSIONS: During the intermittent period, the pharyngeal respiratory pressure in patients with OSAHS during sleep is basically different from the pharyngeal respiratory pressure in normal person. The characteristics of pharyngeal respiratory pressure in intermittent period indicates that both structural and functional abnormalities in pharyngeal cavity in patients with OSAHS, which affect the respiratory airflow during sleep are inherent. The effects are more prominent during onset period, suggesting that the characteristics of the pharyngeal pressure of breathing during the onset period will be more important to the mechanism of airflow obstruction.

[Genetic mutations of homocysteine metabolism related enzymes in patients with ischemic stroke].

To study genetic mutations of methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine-beta-synthase (CBS) T833C related to homocysteine metabolism in patients with ischemic stroke, the MTHFR gene C677T gene mutation and the CBS T833C gene mutation were detected by PCR-RFLP or ARMS method in 74 patients with ischemic stroke and 83 normal people for control. Results showed that the frequencies of MTHFR T homogenetic type (2.7%) , heterogenetic type (51.4%) and T allele (28.4%) in ischemic group were higher than those in control group (1.2%, 39.8% and 21.1%, respectively). The frequencies of CBS C homogenetic type (13.5%) and C allele (43.9%) in ischemic group were higher than those in control group (6.0% and 38.0%, respectively). Multiple Logistic Regression analysis showed that together with the T allele in MTHFR, the C allele in CBS and age were related to ischemic stroke (P<0.05). The odds ratios (OR) of the T allele in MTHFR C677T and the C allele in CBS T833C were 1.74 (95%CI 1.06-2.86) and 1.73 (95%CI 1.07-2.81) respectively. The study revealed that the genetic mutations of MTHFR C677T, CBS T833C,were related with the ischemic stroke. The genetic mutations of MTHFR C677T and CBS T833C may be genetic factors for ischemic stroke.