Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation

Background

The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. In this study, we aimed to assess the circulating levels of fetuin-A and its expression in subcutaneous adipose tissue (SAT) from diabetic and non-diabetic obese subjects and their modulation by exercise.

Methods

SAT and blood were obtained from adults obese (diabetic, n=118 and non-diabetic, n=166) before and after a 3-month exercise program (diabetic, n=40 and non-diabetic, n=36, respectively). Plasma fetuin-A was assayed using ELISA. The presence and expression of fetuin-A in SAT, peripheral blood mononuclear cells (PBMCs) and cell lines (3T3-L1, THP-1, HepG2, RAW 264.7) were analysed using confocal microscopy, immunoblotting and qRT-PCR.

Results

Plasma fetuin-A level did not significantly differ between diabetic and non-diabetic obese subjects. However, when the non-diabetic group was divided into metabolically healthy and unhealthy phenotypes, significantly higher fetuin-A level was observed in the unhealthy sub-group. Circulating fetuin-A was mainly associated with glycaemic markers. In SAT, fetuin-A protein level was significantly higher in the diabetic obese subjects but its mRNA was not detected. Similarly, fetuin-A protein was detected in PBMCs, but its mRNA was not. In line with this, the use of various cell lines and culture media indicated that the presence of fetuin-A in SAT and PBMCs was due to its uptake from circulation rather than its endogenous expression. Finally, physical exercise decreased fetuin-A levels in both plasma and SAT in both groups.

Conclusions

Fetuin-A levels increased in association with diabetes in SAT but not in circulation in the obese subjects. Moreover, physical exercise decreased fetuin-A level. Fetuin-A potentially acts as a hepatokine taken up by other tissues, such as adipose tissue.

     

Cerebral sinus thrombosis in scleroderma: a case report

Scleroderma or systemic sclerosis is a multisystem disease due to excessive collagen deposition in different organs and autoimmunity by production of autoantibodies.According to previous reports, brain is rarely affected in scleroderma, however recent studies show central nervous system can be affect not only as a complication of systemic involvement (hypertension, renal failure) but also as a primary manifestation. In scleroderma, thrombus formation in central nervous system and peripheral systems is uncommon may be due to endothelial cells damage which causes to release antithrombotic factors. We discuss a scleroderma patient with high titter of anticardiolipin antibody who developed to cerebral sinus thrombosis and cerebellum infarction. Then we review literature for both primary brain involvement and thrombotic event in systemic sclerosis.     

Drug discovery technologies and strategies for Machupo virus and other New World arenaviruses

INTRODUCTION: Seven arenaviruses cause viral hemorrhagic fever in humans: the Old World arenaviruses Lassa and Lujo, and the New World Clade B arenaviruses Machupo (MACV), Junín (JUNV), Guanarito (GTOV), Sabiá (SABV), and Chapare (CHPV). All of these viruses are Risk Group 4 biosafety pathogens. MACV causes human disease outbreak with high case-fatality rates. To date, at least 1,200 cases with ≈200 fatalities have been recorded. AREAS COVERED: This review summarizes available systems and technologies for the identification of antivirals against MACV. Furthermore, the article summarizes animal models that have been used for the in vivo evaluation of novel inhibitors. The article highlights present treatments for arenaviral diseases and provides an overview of efficacious small molecules and other therapeutics reported to date. Finally, the article summarizes strategies to identify novel inhibitors for anti-arenaviral therapy. EXPERT OPINION: New high-throughput approaches to quantitate infection rates of arenaviruses, as well as viruses modified to carry reporter genes, will accelerate compound screens and drug discovery efforts. RNAi, gene expression profiling and proteomics studies will identify host targets for therapeutic intervention. New discoveries in the cell entry mechanism of MACV and other arenaviruses as well as extensive structural studies of arenaviral L and NP could facilitate the rational design of antivirals effective against all pathogenic New World arenaviruses.     

Enhanced Loading and Release of Non‐Steroidal Anti‐Inflammatory Drugs from Silica‐Based Nanoparticle Carriers

Silica nanoparticles can be potentially considered the carriers of controlled drug systems. In this research, non‐steroidal anti‐inflammatory drugs were used. Diclofenac sodium and piroxicam were loaded on the considered nanosilica using solvent evaporation method. To prove drug encapsulation on the nanosilica and its rate, infrared spectroscopy, X‐ray diffraction, and BET were used, and after proving the existence of the drug in the nanosilica matrix and determining the amount of loading, dissolution test was performed in an environment similar to that of stomach and intestine in terms of pH. Drug loading percentage showed that over 90% of drugs were loaded on nanosilica. Dissolution tests in stomach pH environment showed the control samples (drug without SBA‐15) released considerable amount of drugs (about 90%) within first 15 min, when it was about 10–20% for the matrixes. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples. It was indicated nanosilica has the ability of retaining the drugs in acidic pH and prevented their release. Furthermore, the drugs were released in a controlled manner in small intestine, which is the main absorption site.     

Correlation of body temperature with protection against staphylococcal enterotoxin B exposure and use in determining vaccine dose-schedule

The immunoprotective potential of a recombinant vaccine against the incapacitating effect of aerosolized staphylococcal enterotoxin B (SEB) in nonhuman primates is reported. SEB belongs to a family of structurally related superantigens responsible for serious, life threatening pathologies. Injecting the recombinant SEB vaccine did not induce temperature elevation in rhesus monkeys, a classical symptom of toxic-shock syndrome. No temperature elevation was noted following injection with control tetanus toxoid. In addition to 100% survival, we observed a clear correlation between vaccine dose and mitigation of temperature elevation after a lethal SEB aerosol challenge. We conclude that the recombinant SEB vaccine is non-pyrogenic and that monitoring changes in body temperature is an important biomarker of toxic shock in a primate animal model.     

Immune protection, natural products, and skin cancer: is there anything new under the sun?

Non-melanoma skin cancers such as squamous cell carcinoma and basal cell carcinoma are the most common types of human neoplasms, representing one third of all new malignancies diagnosed in the US. The number of new cases diagnosed per year in the US alone is approaching one million and continues to rise. Ultraviolet (UV) radiation from the sun is a major cause of non-melanoma skin cancer in humans. Aside from the mutagenic effects of UV radiation, there are suggestions from clinical studies and evidence in animal models that the immune system plays an important role in preventing skin cancer development and progression, and is suppressed by cutaneous exposure to UV radiation. In this article, we review the research on new and existing agents that are being developed to protect the skin immune response from suppression by UV radiation. We also discuss the current state of knowledge regarding their mechanism of action in humans as well as animal models of photosuppression, and their efficacy in cancer prevention.     

Lumbar vertebral hemangioma with extradural extension, causing neurogenic claudication: a case report

The authors present a rare case of lumbar vertebral hemangioma extending to the epidural space with a bisected appearance and impinging on thecal sac. This 52-year-old lady presented with one year history of low back pain and bilateral leg radiation. Plain radiography showed vertical linear streaks at L2 vertebral body and axial computed tomography (CT) scan revealed small "polka dot" appearance within the vertebral body. Magnetic resonance imaging (MRI) showed low signal intensity on T1-weighted images in L2 vertebral body which was not characteristic for hemangioma. The patient underwent an L2 laminectomy, spinal canal decompression and posterior spinal instrumentation. This study indicates that lumbar vertebral hemangioma can extend to the epidural space and cause neurologic symptoms. Magnetic resonance imaging may not show diagnostic features, especially in active lesions and plain radiography and CT scan may be helpful.     

Final Effectiveness and Safety Results of NABUCCO: Real-World Data From a Noninterventional,Prospective, Multicenter Study in 697 Patients With Metastatic Breast Cancer Treated With nab-Paclitaxel

Background

One of the most effective chemotherapies for metastatic breast cancer (MBC) is nab-paclitaxel (nab-P), which is approved for treatment of MBC after failure of first-line therapy and when anthracyclines are not indicated. Randomized clinical trials have shown high efficacy and acceptable toxicity. Real-world data of nab-P in MBC, however, are still limited.