Interferon-gamma regulates the levels of bone formation effectors in a stage-dependent manner.

BACKGROUND: Interferon-gamma (IFN-γ) is an immune-derived cytokines in the innate and adaptive immune responses, and functions as a major pro-inflammatory cytokine. IFNγ has previously been reported involving in the regulation of bone metabolism. However, contradictory results about the roles of IFN-γ in bone formation or bone resorption have been reported. It is possible that the functions of IFN-γ in bone formation is dose-dependent or time-dependent. In this study we examined the effect of IFN-γ on different stages of osteoblastogenesis and bone formation. MATERIALS AND METHODS: Cell proliferation, gene expression and protein levels of the critical effectors involving in different stages of differentiation were compared between differentiating preosteoblast MC3T3-E1 treated with or without IFN-γ at different stages. Cell proliferation were determined by MTT assay. Expression levels of osteoblast differentiation markers was performed by quantitative PCR assay. Also, western blot was conducted to investigate the protein levels in those effectors. CONCLUSION: IFN-γ regulates osteoblast and bone formation in a stage-dependent manner. IFN-γ did not alter and the expression of critical osteogenic transcription factors, such as Runx2 and Cbfb, suggesting that the differentiation was not disrupted by IFN-γ. The cell number and the levels of matrix proteins, including COL1A and BSP, at both early and late stage of osteoblastogenesis were downregulated by IFN-γ, indicating its negative regulating roles in early stages. In contrast, the mineralization protein ALP and OCN was upregulated at late stages. The results suggested that IFN-γ might act as a negative regulator in osteoblast differentiation and bone formation at early stages but switch into positive regulator at late stage. Our data revealed the complex features of the effects of IFN-γ on osteoblast differentiation. The detailed mechanisms of how IFN-γ influence on the bone formation and balance of bone remodeling will be further studied.

First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan.

An outbreak of respiratory illness proved to be infected by a 2019 novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19), was notified first in Wuhan, China, and has spread rapidly in China and to other parts of the world. Herein, we reported the first confirmed case of novel coronavirus pneumonia (NCP) imported from China in Taiwan. This case report revealed a natural course of NCP with self-recovery, which may be a good example in comparison with medical treatments.

Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus.

PM2.5 travels along the respiratory tract and enters systemic blood circulation. Studies have shown that PM2.5 increases the incidence of various diseases not only in adults but also in newborn infants. It causes chronic inflammation in pregnant women and retards fetal development. In this study, pregnant rats were exposed to PM2.5 for extended periods of time and it was found that PM2.5 exposure increased immune cells in mother rats. In addition, cytokines and free radicals rapidly accumulated in the amniotic fluid and indirectly affected the fetuses. The authors collected cerebral cortex and hippocampus samples at E18 and analyzed changes of miRNA levels. Expression levels of cortical miR-6315, miR-3588, and miR-466b-5p were upregulated, and positively correlated with the genes Pkn2 (astrocyte migration), Gorab (neuritogenesis), and Mobp (allergic encephalomyelitis). In contrast, PM2.5 decreased expression of miR-338-5p and let-7e-5p, both related to mental development. Further, PM2.5 exposure increased miR-3560 and let-7b-5p in the hippocampus, two proteins that regulate genes Oxct1 and Lin28b that control ketogenesis and glycosylation, and neural cell differentiation, respectively. miR-99b-5p, miR-92b-5p, and miR-99a-5p were decreased, leading to reduced expression of Kbtbd8 and Adam11 which reduced cell mitosis, migration, and differentiation, and inhibited learning abilities and motor coordination of the fetus. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1412-1425, 2017.

Creating two-dimensional solid helium via diamond lattice confinement.

The universe abounds with solid helium in polymorphic forms. Therefore, exploring the allotropes of helium remains vital to our understanding of nature. However, it is challenging to produce, observe and utilize solid helium on the earth because high-pressure techniques are required to solidify helium. Here we report the discovery of room-temperature two-dimensional solid helium through the diamond lattice confinement effect. Controllable ion implantation enables the self-assembly of monolayer helium atoms between {100} diamond lattice planes. Using state-of-the-art integrated differential phase contrast microscopy, we decipher the buckled tetragonal arrangement of solid helium monolayers with an anisotropic nature compressed by the robust diamond lattice. These distinctive helium monolayers, in turn, produce substantial compressive strains to the surrounded diamond lattice, resulting in a large-scale bandgap narrowing up to ~2.2 electron volts. This approach opens up new avenues for steerable manipulation of solid helium for achieving intrinsic strain doping with profound applications.

Rab5A is associated with axillary lymph node metastasis in breast cancer patients.

The expression of Rab proteins has been associated with cancer. However, few data are available on Rab5A expression in human breast cancer or its impact on disease progression. First, we examined the functional role of Rab5A in breast cancer cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal growth factor in a dose-dependent manner. The epidermal growth factor-induced increase of Rab5A expression correlated well with enhanced migration in wound healing migration assays in these cells. Furthermore, we evaluated the expression of Rab5A in breast cancer specimens using immunohistochemical staining, then analyzed the relationship between the expression of Rab5A and clinicopathological parameters. The increased expression of Rab5A protein in 123 breast cancer samples was associated with higher histological grade (P = 0.004), more lymphovascular invasion (P = 0.027), more axillary lymph node (LN) metastasis (P = 0.008), and a higher number of axillary LN metastases (P = 0.043). Among 218 axillary LNs of more than 10 breast cancer patients with node metastases, 167 metastatic LNs were found to have increased Rab5A expression. Rab5A is associated with axillary LN metastasis in breast cancer patients.

APQS consensus regarding patient shielding during routine radiographic imaging.

Shielding, particularly of the gonads, has been a routine part of diagnostic radiographic imaging for many years. However, recent thinking suggests that such shielding may offer little benefit, and in some cases may actually cause harm, e.g. by obscuring anatomy or paradoxically increasing patient radiation dose secondary to the need for repeat imaging. This thinking has led many institutions in the West to abandon routine shielding. However, in Asia, shielding is still commonplace. It was felt that the Asia-Pacific Forum on Quality and Safety in Medical Imaging (APQS) was an ideal place to discuss the merits of shielding and deliver a pan-Asian consensus. The APQS is an annual meeting that convenes radiation safety and imaging quality experts from all of the major Asian regions. During the 2020 APQS meeting, radiation safety experts from each region discussed their opinions of shielding during a dedicated session. These experts' views were mostly in line with the views of Western radiologists. However, important country specific and cultural factors were noted by each of the experts. A pan-Asian consensus was issued by the forum. It is hoped that this consensus will guide the development of future shielding policies throughout Asia.

Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation.

Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.

Suitability of boric acid as a boron drug for boron neutron capture therapy for hepatoma.

Hepatoma is the second leading cause of cancer death worldwide. Due to the poor outcomes of patients with late diagnosis, newer treatments for hepatoma are still needed. As an emerging therapy, boron neutron capture therapy (BNCT) may be an effective solution in hepatoma management. In this study, boric acid (BA) was used as the boron drug for in vivo analysis of action mechanism. The N1S1 single liver tumor-bearing rat and the VX2 multifocal liver tumor-bearing rabbit models were used to investigate the retention status of BA in the tumor regions during BNCT. The autoradiographic examination showed BA can localize specifically not only in the hepatoma cells but also in tumor blood vessels. Our findings indicate that superior hepatoma targeting could be achieved in BA-mediated BNCT, which supports BA to be a suitable boron drug for BNCT for hepatoma.

Therapeutic Efficacy and Radiobiological Effects of Boric Acid-mediated BNCT in a VX2 Multifocal Liver Tumor-bearing Rabbit Model.

BACKGROUND/AIM: Most patients with hepatocellular carcinoma (HCC) cannot be treated using traditional therapies. Boron neutron capture therapy (BNCT) may provide a new treatment for HCC. In this study, the therapeutic efficacy and radiobiological effects of boric acid (BA)-mediated BNCT in a VX2 multifocal liver tumor-bearing rabbit model are investigated. MATERIALS AND METHODS: Rabbits were irradiated with neutrons at the Tsing Hua Open Pool Reactor 35 min following an intravenous injection of BA (50 mg 10B/kg BW). The tumor size following BNCT treatment was determined by ultrasonography. The radiobiological effects were identified by histopathological examination. RESULTS: A total of 92.85% of the tumors became undetectable in the rabbits after two fractions of BNCT treatment. The tumor cells were selectively eliminated and the tumor vasculature was collapsed and destroyed after two fractions of BA-mediated BNCT, and no injury to the hepatocytes or blood vessels was observed in the adjacent normal liver regions. CONCLUSION: Liver tumors can be cured by BA-mediated BNCT in the rabbit model of a VX2 multifocal liver tumor. BA-mediated BNCT may be a breakthrough therapy for hepatocellular carcinoma.

Treatment of massive retroperitoneal hemorrhage from adrenal metastasis of hepatoma.

Spontaneous rupture of metastatic adrenal tumor with massive retroperitoneal hemorrhage and shock is an uncommon clinical event. Herein, we report a case of hepatocellular carcinoma (HCC), where left hepatic lobectomy and right adrenalectomy for metastatic HCC were performed in April and August 2002, respectively. Subsequently, the patient presented to the emergency room with acute-onset severe left flank and back pain in March 2004, accompanied by a falling hemoglobin level. Computed tomography revealed a 7-cm left adrenal tumor mass with retroperitoneal hemorrhage. The ruptured adrenal tumor was further confirmed by selective angiography, which demonstrated that the bleeder was supplied by the left suprarenal artery. Transarterial embolization (TAE) to stop tumor bleeding was performed successfully. The patient then underwent tumor resection with left adrenalectomy 5 days after the embolization, with pathology subsequently revealing metastatic HCC. The recurrent intrahepatic HCC was controlled with TAE, and the patient underwent hormone replacement therapy with prednisolone 10 mg/day. Metastatic adrenal tumor bleeding should be suspected in hepatoma patients who suffer abrupt flank pain and shock. Hemodynamically unstable patients require supportive transfusions and urgent surgical exploration. Angiographic embolization, if deemed feasible, may be a valuable adjunct for achievement of hemostasis prior to definite surgery.

Automatic Detection of Calcaneal-Fifth Metatarsal Angle Using Radiograph: A Computer-Aided Diagnosis of Flat Foot for Military New Recruits in Taiwan.

Flatfoot (pes planus) is one of the most important physical examination items for military new recruits in Taiwan. Currently, the diagnosis of flatfoot is mainly based on radiographic examination of the calcaneal-fifth metatarsal (CA-MT5) angle, also known as the arch angle. However, manual measurement of the arch angle is time-consuming and often inconsistent between different examiners. In this study, seventy male military new recruits were studied. Lateral radiographic images of their right and left feet were obtained, and mutual information (MI) registration was used to automatically calculate the arch angle. Images of two critical bones, the calcaneus and the fifth metatarsal bone, were isolated from the lateral radiographs to form reference images, and were then compared with template images to calculate the arch angle. The result of this computer-calculated arch angle was compared with manual measurement results from two radiologists, which showed that our automatic arch angle measurement method had a high consistency. In addition, this method had a high accuracy of 97% and 96% as compared with the measurements of radiologists A and B, respectively. The findings indicated that our MI registration measurement method cannot only accurately measure the CA-MT5 angle, but also saves time and reduces human error. This method can increase the consistency of arch angle measurement and has potential clinical application for the diagnosis of flatfoot.