Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovarian Syndrome: A Narrative Review.

Polycystic ovarian syndrome (PCOS) has been estimated to affect 10-15 percent of women in the U.S. Emerging research has found higher rates of nonalcoholic fatty liver disease (NAFLD) among PCOS individuals. While the mechanism continues to be poorly understood the aim of this review is to convey the most recent knowledge regarding the pathogenesis, diagnosis, and treatments for NAFLD in PCOS patients. Elements of insulin resistance, hyperandrogenism, obesity, and chronic inflammation are culprits in the pathogenesis of NAFLD in these patients therefore early liver screening and diagnosis is essential. Although liver biopsy remains the gold standard, advances in imaging modalities show accurate diagnosis and some can even assess the risk of progression to cirrhotic states. Apart from lifestyle modifications resulting in weight loss, other treatments with bariatric surgery, thiazolidinediones, angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARBs), and vitamin E show promising results.

Normalized neutral lipid quantitation by flow cytometry.

Interest in measuring tissue lipids has increased as the link between fat-laden tissues and metabolic disease has become obvious; however, linking disease to a specific cell type within a tissue has been hampered by methodological limitations. Flow cytometry (FC) has been used to assess relative lipid levels in cells. Unfortunately, its usefulness is limited because comparisons between samples generated over several hours is problematic. We show that: 1) in lipophilic fluorophore stained cells, fluorescence intensity measured by FC reflects lipid levels; 2) this technique can be used to assess lipid levels in a mixed cell population; 3) normalizing to a control condition can decrease experiment-to-experiment variation; and 4) fluorescence intensity increases linearly with lipid levels. This allows triacylglycerol (TG) mass to be estimated in mixed cell populations comparing cells with known fluorescence and TG levels. We exploited this strategy to estimate lipid levels in monocytes within a mixed population of cells isolated from human blood. Using this strategy, we also confirmed that perilipin (PLIN)1 increases TG accumulation by ectopically expressing fluorescently tagged PLIN1 in Huh7 cells. In both examples, biochemically assaying for TG in specific cell populations is problematic due to limited cell numbers and isolation challenges. Other advantages are discussed.

Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super-infection.

OBJECTIVES: The upper respiratory tract is the major entry site for Streptococcus pyogenes and influenza virus. Vaccine strategies that activate mucosal immunity could significantly reduce morbidity and mortality because of these pathogens. The severity of influenza is significantly greater if a streptococcal infection occurs during the viraemic period and generally viral infections complicated by a subsequent bacterial infection are known as super-infections. We describe an innovative vaccine strategy against influenza virus:S. pyogenes super-infection. Moreover, we provide the first description of a liposomal multi-pathogen-based platform that enables the incorporation of both viral and bacterial antigens into a vaccine and constitutes a transformative development. METHODS: Specifically, we have explored a vaccination strategy with biocompatible liposomes that express conserved streptococcal and influenza A virus B-cell epitopes on their surface and contain encapsulated diphtheria toxoid as a source of T-cell help. The vaccine is adjuvanted by inclusion of the synthetic analogue of monophosphoryl lipid A, 3D-PHAD. RESULTS: We observe that this vaccine construct induces an Immunoglobulin A (IgA) response in both mice and ferrets. Vaccination reduces viral load in ferrets from influenza challenge and protects mice from both pathogens. Notably, vaccination significantly reduces both mortality and morbidity associated with a super-infection. CONCLUSION: The vaccine design is modular and could be adapted to include B-cell epitopes from other mucosal pathogens where an IgA response is required for protection.