Background and Objectives
A chalazion, also known as a stye, is a common and chronic inflammatory problem of the eyelids where one or more Meibomian glands are blocked. Previous studies have shown that a chalazion is a sign of Meibomian Gland Dysfunction (MGD) and evaporative dry eye disease. The prevalence of chalazia in the pediatric population has recently been noted. In this report, we will describe two pediatric cases of chalazion that are associated with MGD and related dry eye disease.
Methods
This is a case report of non-genetically related 7-year-old and 16-year-old patients as they were each seen for newly developed chalazia.
Results
External exam in both patients showed chalazia, waxy plugs and poor Meibomian gland expression. Meibography showed shorten, truncated, and dilated Meibomian glands with rapid tear break-up times leading to the diagnosis of evaporative dry eye disease due to MGD.
Conclusion
These cases serve to confirm an increase in the prevalence of MGD in the pediatric population and to emphasize the need for early screening for dry eye disease.
Key Words: Chalazion - Meibomian gland dysfunction - Pediatric Dry Eye Disease
Eccentrically biased exercise has been shown to result in delayed onset of muscle damage. This process has been linked to oxidative stress mechanism. However, the effect of antioxidant supplementation on oxidative stress in the skeletal muscle after eccentrically biased exercise has not been investigated. In addition, the effect in different muscle fiber types has not been compared. PURPOSE To determine if antioxidant supplementation can influence oxidative stress markers in different fiber types of rat skeletal muscle after downhill running. METHODS Sixty-six young male Sprague-Dawley rats were pretreated with either a normal diet or an antioxidant diet (2000 mg vitamin C plus 1000 IU vitamin E/g diet) for 2 weeks. Exercised rats ran 90 minutes on a rodent treadmill at a speed of 16 m/min at −16° grade. The rats were sacrificed at before (rested), immediately, 2 hours, and 48 hours post-exercise. Concentrations of malondialdehyde (MDA), protein carbonyls (PC), total glutathione (TGSH) and oxidized glutathione (GSSG) in vastus lateralis (white fast-twitch), vastus intermedius (red fast-twitch), and soleus (slow-twitch) muscles were measured. A 2 x 4 ANOVA was used to analyze the data. RESULTS PC concentration in vastus intermedius (rested =2.46 ± 0.16 nmol/mg protein, 2hr = 3.35 ± 0.24 nmol/mg protein) and soleus (rested =3.04 ± 0.22 nmol/mg protein, 2hr = 4.22 ± 0.33 nmol/mg protein) significantly increased 36% and 39% after downhill running. No changes in MDA concentrations and glutathione status were observed. Antioxidant supplementation significantly decreased PC concentrations in both vastus intermedius and soleus muscles, but did not significantly influence muscle MDA and glutathione status. CONCLUSION These data indicate that 90 minutes of downhill running resulted in protein oxidation in red fast-twitch and slow-twitch muscles of the rats and two weeks of antioxidant pretreatment reduced protein carbonyls in these muscles. (Supported in part by Susan Stout Research Fellowship from UNC-Greensboro)
It is unknown which post-transcriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate post-transcriptional RNA metabolism within ribonucleoprotein networks, are essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to Lin28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 is a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 were able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore NRASG12V/Tp53 cancer formation in Lin28a/b deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver.
Purpose – It is widely acknowledged that the pace of change due to complexity in the competitive environment coupled with advances in technology and innovation is forcing management to rethink strategy formulation and implementation. The purpose of this paper is to discuss convergence in the context of discontinuous competitive environment and possible management responses to changes.
Malignant cells exhibit major metabolic alterations. The regulatory gene networks that regulate metabolism and the impact of these alterations on overall cellular fitness deserve further exploration. The let-7 microRNAs and their antagonists, the Lin28 RNA-binding proteins, are well-known for controlling the timing of embryonic development. This pathway has recently been shown to regulate glucose metabolism in adult mice and to reprogram metabolism during tissue injury and repair. In addition, many lines of evidence have established that Lin28 is an oncogene that drives tumorigenesis in part by suppressing let-7. The metabolic underpinnings of this oncogenic program are just beginning to be uncovered. Here, we will review the current understanding of how Lin28 exerts regenerative and oncogenic effects through metabolic mechanisms.
The let-7 family of miRNAs has been shown to be crucial in many aspects of biology, from the regulation of developmental timing to cancer. The available methods to regulate this family of miRNAs have so far been mostly genetic and therefore not easily performed experimentally. Here, we describe a small molecule screen designed to identify regulators of let-7 targets in human cells. In particular, we focused our efforts on the identification of small molecules that could suppress let-7 targets, as these could serve to potentially intercede in tumors driven by loss of let-7 activity. After screening through roughly 36,000 compounds, we identified a class of phosphodiesterase inhibitors that suppress let-7 targets. These compounds stimulate cAMP levels and raise mature let-7 levels to suppress let-7 target genes in multiple cancer cell lines such as HMGA2 and MYC. As a result, these compounds also show growth inhibitory activity on cancer cells.
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