Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes Treg development.

Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in the United States in young adults, but current treatments are only partially effective, making it necessary to develop new, innovative therapeutic strategies. Myelin-specific interleukin (IL)-17-producing T helper type 17 (Th17) cells are a major subset of CD4 T effector cells (Teff ) that play a critical role in mediating the development and progression of MS and its mouse model, experimental autoimmune encephalomyelitis (EAE), while regulatory T cells (Treg ) CD4 T cells are beneficial for suppressing disease. The IL-6/signal transducer and activator of transcription 3 (STAT-3) signaling pathway is a key regulator of Th17 and Treg cells by promoting Th17 development and suppressing Treg development. Here we show that three novel small molecule IL-6 inhibitors, madindoline-5 (MDL-5), MDL-16 and MDL-101, significantly suppress IL-17 production in myelin-specific CD4 T cells in a dose-dependent manner in vitro. MDL-101 showed superior potency in suppressing IL-17 production compared to MDL-5 and MDL-16. Treatment of myelin-specific CD4 T cells with MDL-101 in vitro reduced their encephalitogenic potential following their subsequent adoptive transfer. Furthermore, MDL-101 significantly suppressed proliferation and IL-17 production of anti-CD3-activated effector/memory CD45RO+ CD4+ human CD4 T cells and promoted human Treg development. Together, these data demonstrate that these novel small molecule IL-6 inhibitors have the potential to shift the Teff  : Treg balance, which may provide a novel therapeutic strategy for ameliorating disease progression in MS.

Burden of decompensated cirrhosis and ascites on hospital services in a tertiary care facility: time for change?

BACKGROUND: Ascites, the most frequent complication of cirrhosis, is associated with poor prognosis and reduced quality of life. Recurrent hospital admissions are common and often unplanned, resulting in increased use of hospital services. AIMS: To examine use of hospital services by patients with cirrhosis and ascites requiring paracentesis, and to investigate factors associated with early unplanned readmission. METHODS: A retrospective review of the medical chart and clinical databases was performed for patients who underwent paracentesis between October 2011 and October 2012. Clinical parameters at index admission were compared between patients with and without early unplanned hospital readmissions. RESULTS: The 41 patients requiring paracentesis had 127 hospital admissions, 1164 occupied bed days and 733 medical imaging services. Most admissions (80.3%) were for management of ascites, of which 41.2% were unplanned. Of those eligible, 69.7% were readmitted and 42.4% had an early unplanned readmission. Twelve patients died and nine developed spontaneous bacterial peritonitis. Of those eligible for readmission, more patients died (P = 0.008) and/or developed spontaneous bacterial peritonitis (P = 0.027) if they had an early unplanned readmission during the study period. Markers of liver disease, as well as haemoglobin (P = 0.029), haematocrit (P = 0.024) and previous heavy alcohol use (P = 0.021) at index admission, were associated with early unplanned readmission. CONCLUSION: Patients with cirrhosis and ascites comprise a small population who account for substantial use of hospital services. Markers of disease severity may identify patients at increased risk of early readmission. Alternative models of care should be considered to reduce unplanned hospital admissions, healthcare costs and pressure on emergency services.

Circular RNA hsa_circ_0011946 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA hsa_circ_0011946 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA, by Y. Meng, E.-Y. Zhao, Y. Zhou, D.-X. Qiang, S. Wang, L. Shi, L.-Y. Jiang, L.-J. Bi, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1226-1232-DOI: 10.26355/eurrev_202002_20175-PMID: 32096152" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20175.

Circular RNA hsa_circ_0011946 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA.

OBJECTIVE: The importance of circular RNAs in malignant tumors has been well concerned nowadays. Oral squamous cell carcinoma (OSCC) is diagnosed prevalently in the world. Our study aims to uncover the potential functions of hsa_circ_0011946 in OSCC development. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to determine the level of hsa_circ_0011946 in OSCC tissues and cell lines. Hsa_circ_0011946 was knocked down in OSCC cells. Biological functions of hsa_circ_0011946 in OSCC were identified by performing cell proliferation assay, colony formation assay, wound healing assay, and transwell assay. The underlying mechanism of hsa_circ_0011946 in regulating OSCC progression was explored by RT-qPCR and Western blot assay. RESULTS: Hsa_circ_0011946 was highly expressed in OSCC tissues compared with adjacent samples. It was also upregulated in OSCC cell lines. The knockdown of hsa_circ_0011946 inhibited cell growth, migration, and invasion in OSCC. The expression of PCNA was reduced via knockdown of hsa_circ_0011946. Furthermore, the expression of PCNA in tumor tissues was positively correlated to the expression of hsa_circ_0011946. CONCLUSIONS: Hsa_circ_0011946 could promote cell growth, migration, and invasion of OSCC by upregulating PCNA, which may offer a new therapeutic intervention for OSCC patients.

Preliminary report on the effect of Nd: YAG laser irradiation on canine tooth pulps.

OBJECTIVE: To study the effects of Nd: YAG laser irradiation on the canine tooth pulps. METHODS: The crown pulp of dog was exposed and excised by ND: YAG laser irradiation. Histopathological examination was used to check changes of the tissues in root canal and periodontium. RESULTS: The pulp of the crown could be successfully excised by Nd: YAG laser without harmful changes in either root canal or periodontal tissues. CONCLUSION: This study may provide an experimental basis for the clinical possibility of crown pulp excision by using Nd: YAG laser irradiation.