Roles of Tumor Suppressor Signaling on Reprogramming and Stemness Transition in Somatic Cells

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Management of Bell’s Palsy with Phototherapy

Bell’s palsy (BP) is a common condition; its incidence rate has increased during the COVID-19 pandemic. The standard treatment for facial nerve palsy includes corticosteroids alone or in combination with antiviral agents. However, the treatment is contraindicated in some patients, including hypertensive or diabetic patients. Also, the medication combination may result in inadequate recovery when complementary and alternative approaches are indicated. This chapter reviewed the literature on managing BP with different types of photobiomodulation (PBM) therapies. Fourteen papers were included. The results show that despite the different kinds of photo energy used, varying laser parameters, and the heterogeneity of patients, the outcome of PBM was similar among studies. Of interest is that acute and subacute BP respond more favorably to PBM than chronic cases. Hence, it is suggested to apply PMB as a complementary treatment in the early stage of the disease to enhance the recovery rate of BP patients. However, the risk of bias in these studies was relatively high. Therefore, further randomized, double-blind placebo-controlled studies are needed to determine the effectiveness of PBM in treating BP

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome.BackgroundSevere acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection.MethodsWe conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy.ResultsAmong these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS.ConclusionAcute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS

MicroRNA profiling study reveals MIR-150 in association with metastasis in nasopharyngeal carcinoma

© 2017 The Author(s). MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in pathogenesis of human cancers. Several miRNAs have been shown to involve in nasopharyngeal carcinoma (NPC) pathogenesis through alteration of gene networks. A global view of the miRNA expression profile of clinical specimens would be the best way to screen out the possible miRNA candidates that may be involved in disease pathogenesis. In this study, we investigated the expression profiles of miRNA in formalin-fixed paraffin-embedded tissues from patients with undifferentiated NPC versus non-NPC controls using a miRNA real-time PCR platform, which covered a total of 95 cancer-related miRNAs. Hierarchical cluster analysis revealed that NPC and non-NPC controls were clearly segregated. Promisingly, 10 miRNA candidates were differentially expressed. Among them, 9 miRNAs were significantly up-regulated of which miR-205 and miR-196a showed the most up-regulated in NPC with the highest incidence percentage of 94.1% and 88.2%, respectively, while the unique down-regulated miR-150 was further validated in patient sera. Finally, the in vitro gain-of-function and loss-of-function assays revealed that miR-150 can modulate the epithelial-mesenchymal-transition property in NPC/HK-1 cells and led to the cell motility and invasion. miR-150 may be a potential biomarker for NPC and plays a critical role in NPC tumourigenesis.Link_to_subscribed_fulltex

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn2+ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn2+ chelator to create an EBNA1-specific inhibitor (ZRL5P4). ZRL5P4 by itself is sufficient to reactivate EBV from its latent infection. ZRL5P4 is able to emit unique responsive fluorescent signals once it binds with EBNA1 and a Zn2+ ion. ZRL5P4 can selectively disrupt the EBNA1 oligomerization and cause nasopharyngeal carcinoma (NPC) tumor shrinkage, possibly due to EBV lytic induction. Dicer1 seems essential for this lytic reactivation. As can been seen, EBNA1 is likely to maintain NPC cell survival by suppressing viral reactivation

THY1 (CD90) Maintains the Adherens Junctions in Nasopharyngeal Carcinoma via Inhibition of SRC Activation

We had previously shown that THY1 (CD90) is a tumor suppressor in nasopharyngeal carcinoma (NPC) and that its down-regulation and loss of expression are associated with tumor metastasis, yet the mechanism leading to such effects remains unknown. In this study we show that tumor invasion could be suppressed by THY1 via adherens junction formation in a few NPC cell lines, and knockdown of THY1 would disrupt this cell-cell adhesion phenotype. Mechanistically, the activity of the SRC family kinase (SFK) member, SRC, and canonical Wnt signaling were dramatically reduced when THY1 was constitutively expressed. Previous studies by others have found that high levels of SRC activity in NPCs are associated with EMT and a poor prognosis. We hypothesized that THY1 can suppress tumor invasion in NPC via inhibition of SRC. By gene silencing of SRC, we found that the in vitro NPC cell invasion was significantly reduced and adherens junctions were restored. Through proteomic analysis, we identified that platelet-derived growth factor receptor β (PDGF-Rβ) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) are novel and potential binding partners of THY1, which were subsequently verified by co-immunoprecipitation (co-IP) analysis. The ligand of PDGF-Rβ (PDGF-BB) could highly induce SRC activation and NPC cell invasion, which could be almost completely suppressed by THY1 expression. On the other hand, the PTPN22 siRNA could enhance both the SRC activities and the cell invasion and could also disrupt the adherens junctions in the THY1-expressing NPC cells; the original THY1-induced phenotypes were reverted when the PTPN22 expression was reduced. Together, our results identified that PTPN22 is essential for THY1 to suppress cell invasion and SRC activity, maintain tight adherens junctions, and prevent NPC metastasis. These results suggested that PDGF-Rβ and SRC can be used as drug targets for suppressing NPC metastasis. Indeed, our in vivo assay using the SRC inhibitor KX2-391, clearly showed that inhibition of SRC signaling can prevent the metastasis of NPC, indicating that targeting SRC can be a promising approach to control the NPC progression