Therapeutic Opportunities for Targeting microRNAs in Cancer

MicroRNAs (miRNAs) are small noncoding RNAs that can function as either powerful tumor promoters or suppressors in numerous types of cancer. The ability of miRs to target multiple genes and biological signaling pathways has created intense interest in their potential clinical utility as predictive and diagnostic biomarkers, and as innovative therapeutic agents. Recently, accumulating preclinical studies have illustrated the feasibility of slowing tumor progression by either overexpressing tumor suppressive miRNAs, or by neutralizing the activities of oncogenic miRNAs in cell- and animal-based models of cancer. Here we highlight prominent miRNAs that may represent potential therapeutic targets in human malignancies, as well as review current technologies available for inactivating or restoring miRNA activity in clinical settings.

Clinical Potential of miRNAs in Human and Infectious Diseases

MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in human disease. Several miRnome profiling studies have identified miRNAs deregulated in cancer and infectious diseases and miRNAs are also involved in regulation of the host response to infection. Thereby, the usage of miRNAs as biomarkers and potential treatments for both human and infectious diseases is under development. This review will provide insights into the contribution of miRNAs to pathogenesis and disease development and will present a general outline of the potential use of miRNAs as therapeutic tools.

Understanding Hydrogen Sulfide in Inflammation: Opportunities and Challenges

Inflammation is an adaptive response to injury, but uncontrolled inflammation can lead to tissue damage and disease. Research in our laboratory (since confirmed in different laboratories worldwide) has shown that hydrogen sulfide (H2S) acts as a mediator of inflammation in different disease conditions. Learning about a novel mediator of inflammation results in unique opportunities with which to approach inflammatory diseases. At the same time, the complexity of biological systems and translation of research from the bed to the bedside also presents challenges. This Editorial aims to discuss the opportunities and challenges in relation to the role of H2S in inflammation, and the future prospects for this research.

Retinoids Induced Cancer Stem Cell Differentiation and Apoptosis for Cancer Therapies

Retinoids show great potential in various kinds of cancer chemotherapy due to its ability to induce signals for cell differentiation or death, as well as inhibit cancer stem cell proliferation. This paper summarized the recent progress of retinoids induced cancer stem cell differentiation and apoptosis in cancer therapy field, with the highlighted novel retinoid named WYC-209 in our lab, which could inhibit the tumor stem cell and malignant melanoma tumors with high efficacy and little toxicity.

Proteomic analysis of extracellular vesicles from medullospheres reveals a role for iron in the cancer progression of medulloblastoma

Background: Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity todisseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed toimprove cure rates and to reduce life-long cognitive and functional deficits associated with current therapies.Extracellular Vesicles (EVs) are important players in cell-to-cell communication in health and diseases. A clearerunderstanding of cell-to-cell communication in tumors can be achieved by studying EV secretion inmedullospheres. This can reveal subtle modifications induced by the passage from adherent to non-adherentgrowth, as spheres may account for the adaptation of tumor cells to the mutated environment.Methods: Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained throughculture conditioning based on low attachment flasks and specialized medium. EVs collected by ultracentrifugation,in adherent conditions and as spheres, were subjected to electron microscopy, NanoSight measurements andproteomics.Results: Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population ofspheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease innumber/size of spheres and in stem cell populations able to initiate in vitro spheres formation.Conclusions: This work suggests a not yet identified role of iron metabolism in MB progression and invasion andopens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.

A prospective, randomized, three arm, open label study comparing the safety and efficacy of PP110, a novel treatment for hemorrhoids to preparation-H® maximum strength cream in the treatment of grade 2–3 hemorrhoids

Background Hemorrhoids are a common disorder that affects the quality of life of millions of people worldwide. The effectiveness of OTC medication is limited and they mainly provide symptomatic relief. In order to treat this ailment, we formulated PP110 Gel and Wipes, as a novel treatment for hemorrhoids. PP110 is based on known active ingredients with a topical film-forming agent designed to provide physical protection and prolonged tissue contact with the active ingredients. Methods PP110 Gel, PP110 Wipes and the comparator Preparation-H® were used on three patient cohorts. Treatment was administered once daily for PP110, and three-four times daily for Preparation-H®, for 14 days. Six different clinical parameters relating to common symptoms of hemorrhoids were monitored. Results PP110 Gel was significantly better than Preparation-H® in reducing bleeding (Δ = 6 %), providing pain relief (Δ = 10 %) and controlling itching (Δ = 11 %). These three parameters are considered as the most common distressing symptoms for hemorrhoids patients, demonstrating that PP110 is superior to conventional treatment. Conclusion This study demonstrated the efficacy of the PP110 Gel in treating hemorrhoids and its superiority to conventional treatments. The PP110 film-based formulation provides a slow-release mechanism and as a consequence, a prolonged therapeutic window. PP110 was both more effective in reducing hemorrhoids symptoms and more convenient to use, in that it only required application once per day.

Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta

Actinidia Chinensis Planch roots (acRoots) are used to treat many cancers, although the antitumor mechanism by which acRoots inhibit cancer cell growth remains unclear. The present study aims at investigating inhibitory effects of acRoots on human lung cancer cells and potential mechanisms. Our data demonstrate that the inhibitory effects of acRoots on lung cancer cells depend on genetic backgrounds and phenotypes of cells. We furthermore found the expression of metabolism-associated gene profiles varied between acRoots-hypersensitive (H460) or hyposensitive lung cancer cells (H1299) after screening lung cancer cells with different genetic backgrounds. We selected retinoic acid receptor beta (RARB) as the core target within metabolism-associated core gene networks and evaluated RARB changes and roles in cells treated with acRoots at different concentrations and timeframes. Hypersensitive cancer cells with the deletion of RARB expression did not response to the treatment with acRoots, while RARB deletion did not change effects of acRoots on hyposensitive cells. Thus, it seems that RARB as the core target within metabolism-associated networks plays important roles in the regulation of lung cancer cell sensitivity to acRoots.

RIPK1 and RIPK3 – emerging targets in cancer?

RIPK1 and RIPK3 are homologous Ser/Thr kinases, which act in concert within the necrosome complexes to initiate a sub-type of regulated necrosis, termed necroptosis. Necroptosis has gradually emerged as a highly clinically relevant form of necrosis, which can be targeted therapeutically. Besides necroptosis, RIPK1 and RIPK3 have been implicated in other pathophysiologically-relevant responses, including regulation of apoptosis and inflammation. More recently, it became evident that RIPK1/RIPK3 pathways may be systematically altered in cancers. Status of these pathways may provide a prognostic value, and therapeutic modulation of RIPK1/RIPK3 signaling may represent a new strategy against various forms of human cancer.

HIV Universal Vaccine

For many deadly viruses, there are no preventive and / or therapeutic vaccines approved by health authorities World-wide (e.g., HIV, Ebola, Dengue, and many others). Although, for some viruses, prophylactic vaccines are very effective (e.g., HBV, Polio, Rota, and many others). In this realm, we design, manufacture, test, and streamline into the clinics novel viral universal vaccines (VUV). VUV have such unique features, that medical vaccination or natural infection induced immunity against some viruses (e.g., HBV) in patients, who became infected with other viruses (e.g., HIV), upon the VUV’s administration , is redirected against these other, newly infecting viruses (e.g., HIV).

The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondriatargeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’ s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.