ß 2 -Microglobulin Participates in the Development of Vestibular Schwannoma by Regulating Nuclear Factor-κB.

BACKGROUND AND OBJECTIVES: Vestibular schwannoma (VS), the most common intercranial schwannoma, originates from the sheath of the vestibular nerve. The growth rate of VS varies greatly, with the tumor enlarging gradually, which can compress the peripheral nerve tissue and reveal corresponding symptoms. This study was aimed to elucidate the growth mechanism of VS by analyzing cellular changes at protein, messenger ribonucleic acid (mRNA), and other molecular levels. METHODS: We determined mRNA and protein levels of ß 2 -microglobulin (ß 2 -M) and nuclear factor κB (NF-κB) in tumors of different sizes using the real-time polymerase chain reaction and Western blotting, respectively. The relationship between these factors was verified in VS primary cells cultured in vitro, and the potential role of ß 2 -M and NF-κB in VS growth was elucidated. RESULTS: In the secretions of freshly isolated tumor tissue cultured for 72 h, the concentration of ß 2 -M was positively correlated with the tumor diameter. Furthermore, tumors with larger diameter showed higher expressions of ß 2 -M and NF-κB at protein and mRNA level. ß 2 -M treatment resulted in elevated protein expression of NF-κB and also its phosphorylated form in vitro. CONCLUSION: ß 2 -M may participate in VS growth by regulating NF-κB and act as a key regulatory molecule in VS tumor growth.

Tooth loss associated with the use of tenofovir disoproxil fumarate.

WHAT IS KNOWN AND OBJECTIVE: The frequent tenofovir disoproxil fumarate (TDF)-related adverse drug reactions (ADRs) are nephrotoxicity and bone toxicity; however, tooth-related ADRs of TDF have not been reported. We describe the case of a 41-year-old Han Chinese man with chronic hepatitis B with TDF-associated tooth loss. CASE SUMMARY: He presented with halitosis, gingival swelling and tooth loss after TDF use. After excluding the possibility of other drug-related ADRs, TDF was considered a possible cause and switched with tenofovir alafenamide fumarate (TAF). After 6 months, the oral symptoms disappeared, with no additional tooth loss. WHAT IS NEW AND CONCLUSION: This is the first report of such ADRs. The ADR score was 7, indicating tooth loss as a potential TDF-related ADR.

The Ca2+/CaMKK2 axis mediates the telbivudine induced upregulation of creatine kinase: Implications for mechanism of antiviral nucleoside analogs' side effect.

Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from creatine kinase (CK) elevation to myopathy. The purpose of this study was to explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on mitochondrial morphology and proteins (TK2 and ß-actin), oxidative stress, intracellular Ca2+ levels, Ca2+-related signaling pathway (CaMKK2/AMPK), and Ca2+-related biomarkers such as superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed in human skeletal muscle cells (HSKMCs). The results showed that LdT induced a dose-dependent increase in CK activity in HSKMCs, without affecting mitochondrial morphology, and TK2 and ß-actin protein levels, following 72 h of treatment. In addition, LdT increased Ca2+ production, ROS generation, MDA and lipid peroxide (LPO) levels, and activated the CaMKK2/AMPK signaling pathway. Moreover, these effects were attenuated by the BAPIA-AM (the calcium chelator). We also confirmed the presence of relevant markers (MDA, LPO, and SOD) in serum from CHB patients after LdT treatment, and found that CK was positively correlated with MDA and LPO, and negatively associated with SOD. These findings indicate that LdT induces CK elevation and oxidative stress associated with imbalance of intracellular Ca2+ in HSKMCs, suggesting that Ca2+/CaMKK2 axis imbalance may underlie human LdT-induced CK elevation. The present findings provide a solid basis for assessing the mechanism of drug-induced CK elevation, which can help develop new tools for the prevention and treatment of diseases associated with drug-induced CK elevation.

Neuronal plasticity and the changes of microenvironment at the ischemic neocortical penumbra after cere- bral artery occlusion in rats / 中国神经精神疾病杂志

Objectives To investigate the effects of nerve nutrient factors and inhibitory factors on neuronal regen? eration and axonal reconstruction at ischemic neocortical penumbra after focal cerebral ischemia in rats. Methods The rat model of middle cerebral artery ischemia was established using suture-occluded method. The pathological morpholo? gy of brain tissue was examined by using HE staining. The expression levels of GAP-43 SYN, nutrient factor (BDNF VEGF Ang1) and inhibitory factor (NogoA NogoR RhoA) were determined by using Western blotting technique. Results The number of neurons in ischemic penumbra was significantly decreased in model group (P<0.01) than in sham-operat? ed group. The expression levels of GAP-43 were significantly decreased (P<0.05) while the expression levels of NogoA NgR and RhoA in the thalamus were significantly increased (P<0.05) in model group than in sham-operated group. The expression levels of SYN and nutrient factors (BDNF VEGF Ang1) were not different between the model group and sham-operated group. Conclusion The increase in nerve inhibitory factors may contribute to the down-regulation of neu?rogenesis at ischemic neocortical penumbra after focal cerebral ischemia in rats.