Abstract: HIV-1 infection is characterized by a continuous viral replication throughout the illness that can be controlled to some extent by effective treatment. Early during primary infection, latent reservoirs where the virus remains hidden in metabolically inert cells are established. These reservoirs are responsible for a low-rate viral replication that can be observed even during effective treatment and are a major obstacle for the complete eradication of the infection. This low-rate viral replication also comes from anatomical sites where drug penetration is limited and only a suboptimal drug concentration can be achieved. Further understanding of the mechanisms underlying HIV-1 latency is of primary importance to develop new strategies that ensure the complete destruction of reservoirs and, therefore, the eradication of the infection. ... Read more

Abstract: Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following human papilloma virus vaccine. ... Read more

Abstract: One-third of humans carry Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) where microbe/host immune response interactions result in persistence or active TB. However, immune mediators associated with human TB remain poorly defined. Through a series of comparative studies of lung immune response of TB cases at the time of diagnosis and patients with other infectious lung diseases and volunteers, we found that TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity critical for containment of M. tuberculosis. Despite the concomitant heightened levels of Th1-type mediators, they are likely rendered ineffectual by high levels of intracellular (e.g., SOCS) and extracellular (e.g., IL-10) immune suppressors. These modulators are a direct response to M. tuberculosis as many suppressive factors declined to the levels of controls by 30 days of anti-TB treatment while most Th1-type and innate immune mediators rose above the pre-treatment levels. Parallel laboratory studies and monitored lung alveolar macrophage effector, nitric oxide synthase-2 (being shown critical for killing M. tuberculosis), support that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type/innate immunity as an immunopathological strategy. Our studies highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response. ... Read more

Abstract: Carbohydrates are ubiquitous and represent the most abundant class of molecules in nature. All cell surfaces are coated with complex carbohydrates where they act as recognition molecules for other cells, functional molecules, and pathogens. Consequently, they are involved in disease indications as diverse as inflammation, cancer, and infectious disease. In general, native carbohydrates lack the properties necessary for efficacious drugs and historically have not been successful candidates to capitalize on these applications. Understanding the bioactive conformation and molecular interactions of functional carbohydrates, however, allows the rational design of small molecule glycomimetics that exhibit improved drug-like properties such as increased affinity, serum half-life, stability, and bioavailability. Recent advances in analytical techniques (i.e., NMR, x-ray crystallization), molecular modeling, and synthetic organic chemistry allow the design of potent glycomimetic compounds, which opens the door to a new class of therapeutic drugs to target molecular mechanisms that can address many of the current unmet needs in the treatment of disease. ... Read more

Abstract: As research techniques and biotechnology advance, the risk for potential bioterrorism increases due to the ease of creating or modifying virulent pathogenic microorganisms. In addition, the destruction of natural habitats to a host of animals and microbial species that are normally sequestered in these areas may bring about new diseases to humans. ... Read more

Abstract: Hepatitis C virus (HCV) infection is a major public health problem around the world and it is estimated that there are about 200 million infections globally. The majority of HCV infected patients develop chronic infection, which can progress to liver cirrhosis, hepatocellular carcinoma, and liver failure. Since the discovery of the virus in 1989, impressive progress has been made in the treatment of HCV hepatitis. However, the actual standard of care in treating HCV infection, represented by the combination therapy of pegylated interferon alpha 2a or 2b with ribavirin, fails to cure near half of treated patients. This paper aimed to trace a brief overview of the progress made by interferon-based treatments for HCV hepatitis since their introduction in the early 1990s, and to highlight the results of recent clinical studies concerning new and emerging drugs. ... Read more

Abstract: Hepatitis C virus (HCV) infects about 2% of the world population or approximately 123 million people. The disease causes a significant level of morbidity and mortality among those afflicted. The combination of interferon and ribavirin is effective in many patients. However, the right treatment doses and duration, among other attributes, have a large impact on the treatment outcome. ... Read more

Abstract: Liver cancer is among the most common malignancies, impacting significantly across all societies worldwide. The lethal impact of this prevalent cancer is unlikely to change considerably in the near future due to a limited understanding of disease pathogenesis on the molecular, cellular, and environmental levels and how current knowledge might be converted into new preventive, therapeutic and diagnostic approaches. This article highlights the current challenges and opportunities in this critical area of unmet need. ... Read more

Abstract: Insufficient concentrations and very short residence time of the anti-retroviral agents at the cellular and anatomical sites are among major factors that contribute to the failure of eradicating HIV from reservoirs and the development of multidrug resistance against antiretroviral agents. In recent years, nanotechnology-based drug delivery systems have shown remarkable ability to overcome many of the same anatomical and physiological barriers and deliver the therapeutic agents locally at the site of systemic diseases such as cancer. ... Read more

Abstract: It has been known for a long time that memory CD8+ T cells are the main players in conferring long-lasting and effective protection against infection with intracellular pathogens. The generation of instantly protective memory cells, so-called effector memory T cells, represents the basic principle of T cell-based vaccination strategies. Therefore, the understanding of the exact mechanisms required for in vivo generation of distinct CD8+ memory T cell subtypes will become the crucial rationale for enhancing the efficiency and quality of vaccine-induced protective immunity. ... Read more