Head and Neck Diseases by Alexandros G.Sfakianakis

Παρασκευή 26 Ιανουαρίου 2018

Two novel microRNA biomarkers related to β-cell damage and their potential values for early diagnosis of type 1 diabetes.

Two novel microRNA biomarkers related to β-cell damage and their potential values for early diagnosis of type 1 diabetes.

J Clin Endocrinol Metab. 2018 Jan 23;:

Authors: Liu L, Yan J, Xu H, Zhu Y, Liang H, Pan W, Yao B, Han X, Ye J, Weng J

Abstract
Context: New strategies and biomarkers are needed in the early detection of β-cell damage in the progress of type 1 diabetes mellitus (T1DM).
Objective: To explore whether serum microRNAs should be served as biomarkers for T1DM.
Design, Settings and Patients: The serum microRNA profile was established with microRNA microarray in discovery phase (6 T1DM, 6 controls). A microRNA-based model for T1DM diagnosis was developed using logistic regression analysis in the training dataset (40 T1DM, 56 controls) and then validated with leave-one-out cross validation and another independent validation dataset (33 T1DM, 29 controls).
Main Outcome Measure(s): Quantitative RT-PCR was applied to confirm the differences of candidate microRNAs between T1DM and controls. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. INS-1 cells, streptozocin-treated mice (n=4) and NOD mice (n=12) were used to evaluate the association of microRNAs with β-cell damage.
Results: A microRNA-based model was established in the training dataset with high diagnostic accuracy for T1DM (AUC=0.817) based on six candidate differential expressed microRNAs identified in discovery phase. The validation dataset showed the model's satisfactory diagnostic performance (AUC=0.804). Secretions of miR-1225-5p and miR-320c were significantly increased in streptozocin-treated mice and INS-1 cells. Noteworthy, the elevation of these two microRNAs was observed before glucose elevation in the progress of diabetes in NOD mice.
Conclusions: Two microRNA biomarkers (miR-1225-5p and miR-320c) related to β-cell damage were identified in recent-onset T1DM patients. The microRNA-based model established in this study exhibited a good performance in diagnosis of T1DM.

PMID: 29370422 [PubMed - as supplied by publisher]

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Gut Microbial Diversity in Women with Polycystic Ovary Syndrome Correlates with Hyperandrogenism.

Gut Microbial Diversity in Women with Polycystic Ovary Syndrome Correlates with Hyperandrogenism.

J Clin Endocrinol Metab. 2018 Jan 23;:

Authors: Torres PJ, Siakowska M, Banaszewska B, Pawelczyk L, Duleba AJ, Kelley ST, Thackray VG

Abstract
Context: A majority of women with polycystic ovary syndrome (PCOS) have metabolic abnormalities that result in an increased risk of developing type 2 diabetes and heart disease. Correlative studies have shown an association between changes in the gut microbiome and metabolic disorders. Two recent studies reported a decrease in alpha diversity of the gut microbiome in women with PCOS compared with healthy women.
Objective: We investigated whether changes in the gut microbiome correlated with specific clinical parameters in women with PCOS compared to healthy women. We also investigated whether there were changes in the gut microbiome in women with polycystic ovarian morphology (PCOM) that lacked the other diagnostic criteria of PCOS.
Participants: Subjects were recruited at the Poznan University of Medical Sciences. Fecal microbial diversity profiles of healthy women (n=48), women with PCOM (n=42), and women diagnosed with PCOS using the Rotterdam criteria (n=73) were analyzed using 16S rRNA gene sequencing.
Results: Lower alpha diversity was observed in women with PCOS compared with healthy women. Women with PCOM had a change in alpha diversity that was intermediate between the other two groups. Regression analyses showed that hyperandrogenism, total testosterone and hirsutism were negatively correlated with alpha diversity. PERMANOVA of UniFrac distances showed that hyperandrogenism was also correlated with beta diversity. Random Forest identified bacteria that discriminated between healthy women and women with PCOS.
Conclusions: These results suggest that hyperandrogenism may play a critical role in altering the gut microbiome in women with PCOS.

PMID: 29370410 [PubMed - as supplied by publisher]

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Access to Safe, Timely, and Affordable Surgical Care in Uganda: A Stratified Randomized Evaluation of Nationwide Public Sector Surgical Capacity and Core Surgical Indicators.

Access to Safe, Timely, and Affordable Surgical Care in Uganda: A Stratified Randomized Evaluation of Nationwide Public Sector Surgical Capacity and Core Surgical Indicators.

World J Surg. 2018 Jan 24;:

Authors: Albutt K, Punchak M, Kayima P, Namanya DB, Anderson GA, Shrime MG

Abstract
BACKGROUND: Access to safe surgery is critical to health, welfare, and economic development. In 2015, the Lancet Commission on Global Surgery recommended that all countries collect surgical indicators to lend insight into improving surgical care. No nationwide high-quality data exist for these metrics in Uganda.
METHODS: A standardized quantitative hospital assessment and a semi-structured interview were administered to key stakeholders at 17 randomly selected public hospitals. Hospital walk-throughs and retrospective reviews of operative logbooks were completed.
RESULTS: This study captured information for public hospitals serving 64.0% of Uganda's population. On average, <25% of the population had 2 h access to a surgically capable facility. Hospitals averaged 257 beds/facilities and there were 0.2 operating rooms per 100,000 people. Annual surgical volume was 144.5 cases per 100,000 people per year. Surgical, anesthetic, and obstetrician physician workforce density was 0.3 per 100,000 people. Most hospitals reported having electricity, oxygen, and blood available more than half the time and running water available at least three quarters of the time. In total, 93.8% of facilities never had access to a CT scan. Sterile gloves, nasogastric tubes, and Foley catheters were frequently unavailable. Uniform outcome reporting does not exist, and the WHO safe surgery checklist is not utilized.
CONCLUSION: The Ugandan public hospital system does not meet LCoGS targets for surgical access, workforce, or surgical volume. Critical policy and programmatic developments are essential to build surgical capacity and facilitate provision of safe, timely, and affordable surgical care. Surgery must become a public health priority in Uganda and other low resource settings.

PMID: 29368021 [PubMed - as supplied by publisher]

http://ift.tt/2DOXpVr

upper respiratory tract infection; +19 new citations

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EphB4: A promising target for upper Aerodigestive malignancies.

EphB4: A promising target for upper Aerodigestive malignancies.

Biochim Biophys Acta. 2018 Jan 21;:

Authors: Salgia R, Kulkarni P, Gill PS

Abstract
The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that include two major subclasses, EphA and EphB. They form an important cell communication system with critical and diverse roles in a variety of biological processes during embryonic development. However, dysregulation of the Eph/ephrin interactions is implicated in cancer contributing to tumour growth, metastasis, and angiogenesis. Here, we focus on EphB4 and review recent developments in elucidating its role in upper aerodigestive malignancies to include lung cancer, head and neck cancer, and mesothelioma. In particular, we summarize information regarding EphB4 structure/function and role in disease pathobiology. We also review the data supporting EphB4 as a potential pharmacological and immunotherapy target and finally, progress in the development of new therapeutic strategies including small molecule inhibitors of its activity is discussed. The emerging picture suggests that EphB4 is a valuable and attractive therapeutic target for upper aerodigestive malignancies.

PMID: 29369779 [PubMed - as supplied by publisher]

http://ift.tt/2Bw8HJ6

PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

Cancer Biol Ther. 2018 Jan 25;:1-8

Authors: Ibrahim S, Li G, Hu F, Hou Z, Chen Q, Li G, Luo X, Hu J, Feng Y

Abstract
Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in different types of human cancer. We previously reported the important role of PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC is still remaining unclear. In this study, we explored online clinical databases to analyze the prognosis differences between higher and lower expression of PIK3R3 in CRC patients. Interestingly, we found that better disease-free survival (DFS) were occurred in patients with higher expression of PIK3R3, but there is no significant difference in overall survival (OS). For further, we showed that PIK3R3 could enhance 5-FU induced apoptosis by regulating the expression of thymmidine phosphorylase (TP). In conclusion, PIK3R3 could be considered as a predictor of 5-FU sensitivity for personalized treatment, and a therapeutic target for colorectal cancer.

PMID: 29370570 [PubMed - as supplied by publisher]

http://ift.tt/2FiB1AX

Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

Cancer Biol Ther. 2018 Jan 25;:1-9

Authors: Liu J, Qu X, Shao L, Hu Y, Yu X, Lan P, Guo Q, Han Q, Zhang J, Zhang C

Abstract
Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.

PMID: 29370558 [PubMed - as supplied by publisher]

http://ift.tt/2DQuMYg