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Moreover, genetic and pathophysiologic inhibition of the HIF-2α-NEU3-ceramide pathway can alleviate insulin resistance, suggesting that these could be potential drug targets for the treatment of metabolic diseases. Herein, the effects of hypoxia and ceramide, especially in the intestine, on metabolic diseases are summarized.Hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider, for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immune-competent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance". However, with regard to HBV and LT, outstanding issues are still on the table (1) A standard HBV prophylaxis protocol after transplant has not yet been clearly defined; (2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs; and (3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.Nonalcoholic steatohepatitis (NASH) is the progressive subtype of non-alcoholic fatty liver disease and potentiates risks for both hepatic and metabolic diseases. Although the pathophysiology of NASH is not completely understood, recent studies have revealed that macrophage activation is a major contributing factor for the disease progression. Macrophages integrate the immune response and metabolic process and have become promising targets for NASH therapy. Natural products are potential candidates for NASH treatment and have multifactorial underlying mechanisms. Macrophage involvement in the development of steatosis and inflammation in NASH has been widely investigated. In this review, we assess the evidence for natural products or their active ingredients in the modulation of macrophage activation, recruitment, and polarization, as well as the metabolic status of macrophages. Our work may highlight the possible natural products that target macrophages as potential treatment options for NASH.Liver transplantation represents the only curative option for patients with end-stage liver disease, fulminant hepatitis and advanced hepatocellular carcinoma. Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period, long-term survival is hampered by the lack of improvement in survival in the late post transplantation period (over 5 years after transplantation). The main etiologies for late mortality are malignancies and cardiovascular complications. The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components (arterial hypertension, dyslipidemia, obesity, renal injury, etc.). Selleckchem SF2312 These comorbidities result from a combination of pre-liver transplant features, immunosuppressive agent side-effects, changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle. In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation, as well as proposing management strategies.Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a dismal prognosis, especially when diagnosed at advanced stages. Annexin A2 (ANXA2), is found to promote cancer progression and therapeutic resistance. However, the underlining mechanisms of ANXA2 in immune escape of HCC remain poorly understood up to now. Herein, we summarized the molecular function of ANXA2 in HCC and its relationship with prognosis. Furthermore, we tentatively elucidated the underlying mechanism of ANXA2 immune escape of HCC by upregulating the proportion of regulatory T cells and the expression of several inhibitory molecules, and by downregulating the proportion of natural killer cells and dendritic cells and the expression of several inhibitory molecules or effector molecules. We expect a lot of in-depth studies to further reveal the underlying mechanism of ANXA2 in immune escape of HCC in the future.Antibiotic-loaded cement spacers are used in two-stage revision knee arthroplasty for infection, but commercially available spacers may not always be suitable for significant bone loss or soft tissue failure in multiply revised cases. We describe a technique for producing an on-table, static, reinforced cement spacer - the 'apple core' spacer - with the intended outcome of providing joint stability in such patients, prior to undertaking a second-stage procedure. Following a radical debridement, the spacer is made of three components (1) a 'central bar' of external fixator connecting rods, combined using cerclage wires as needed; (2) a standard polymethylmethacrylate cement 'apple core'; and (3) a covering 'skin' of high dose antibiotic-loaded cement, which is stippled as it sets, to increase the surface area and facilitate antibiotic elution. This technique was performed in nine patients who underwent two-stage salvage revision for complex, recurrent infected total knee arthroplasty at a single institution. All patients successfully went on to definitive second-stage reimplantation and have retained their limbs. The 'apple core' cement spacer allows massive bone defects to be effectively managed between staged revision procedures.
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