Current Drug Targets - Volume 21, Issue 6, 2020

Dendrimers are emerging class of nanoparticles used in targeted drug delivery systems. These are radially symmetric molecules with well-defined, homogeneous, and monodisperse structures. Due to the nano size, they can easily cross the biological membrane and increase bioavailability. The surface functionalization facilitates targeting of the particular site of action, assists the high drug loading and improves the therapeutic efficiency of the drug. These properties make dendrimers advantageous over conventional drug delivery systems. This article explains the features of dendrimers along with their method of synthesis, such as divergent growth method, convergent growth method, double exponential and mixed method, hyper-core and branched method. Dendrimers are effectively used in anticancer delivery and can be targeted at the site of tumor either by active or passive targeting. There are three mechanisms by which drugs interact with dendrimers, and they are physical encapsulation, electrostatic interaction, chemical conjugation of drug molecules. Drug releases from dendrimer either by in vivo cleavage of the covalent bond between drugdendrimer complexes or by physical changes or stimulus like pH, temperature, etc.

Toxoplasma gondii is a prevalent parasitic pathogen that infected over one-third of the global population. Toxoplasmosis is diagnosed by isolating the parasite and detecting host antibodies. In contrast, the main problem with diagnosis relates to the sensitivity and specificity of the tests. Currently, treatment with pyrimethamine and sulfadiazine is recommended, despite their side effects and toxicity to humans. Moreover, the absence of a vaccine to completely protect against this infection is the main obstacle to the effective treatment and prevention of toxoplasmosis. Recently, nanoparticles and nanomaterials have been studied as delivery systems for the immunization and treatment of T. gondii infections. One of the most important applications of liposomes is drug and vaccine delivery, due to their biodegradability, low inherent toxicity, and immunogenicity. Liposomes are flexible delivery systems and immunological adjuvants able not only to load diverse antigens, such as proteins, peptides, nucleic acids, and carbohydrates but also to combine them with immunostimulators. Liposomes have the incredible potential within the development of modern types of vaccines and numerous endeavors have been made to improve the effectiveness of vaccines in recent years. In this review, we concentrate on the viable targeting strategies of liposome-based vaccine delivery systems to prevent, control and treat toxoplasmosis.

Honokiol and its isomer magnolol are poly-phenolic compounds isolated from the Magnolia officinalis that exert cardiovascular modulating effects via a variety of mechanisms. They are used as blood-quickening and stasis-dispelling agents in Traditional Chinese Medicine and confirmed to have therapeutic potential in atherosclerosis, thrombosis, hypertension, and cardiac hypertrophy. This comprehensive review summarizes the current data regarding the cardioprotective mechanisms of those compounds and identifies areas for further research.

Photoreceptor loss is a major cause of blindness around the world. Stem cell therapy offers a new strategy in retina degenerative disease. Retinal progenitors can be derived from embryonic stem cells (ESC) in vitro, but cannot be processed to a mature state. In addition, the adult recipient retina presents a very different environment than the photoreceptor precursor donor. It seems that modulation of the recipient environment by ectopic development regulated growth factors for transplanted cells could generate efficient putative photoreceptors. The purpose of this review article was to investigate the signaling pathway of growth factors including: insulin-like growth factors (IGFs), fibroblast growth factors (FGF), Nerve growth factor (NGF), Brain-derived neurotrophic factor (BDNF), Taurin and Retinoic acid (RA) involved in the differentiation of neuroretina cell, like; photoreceptor and retinal progenitor cells. Given the results available in the related literature, the differentiation efficacy of ESCs toward the photoreceptor and retinal neurons and the important role of growth factors in activating signaling pathways such as Akt, Ras/Raf1/ and ERKs also inhibit the ASK1/JNK apoptosis pathway. Manipulating differentiated culture, growth factors can influence photoreceptor transplantation efficiency in retinal degenerative disease.

Inflammation is the multifaceted biological response of vascular tissues against injurious stimuli such as pathogens, irritants or infection. However, when inflammation goes away, it leads to produce quite serious life-threatening diseases like Alzheimer's, rheumatoid arthritis, heart attacks, colon cancer, etc. Therefore, inflammation suddenly has become one of the hottest areas of medical research. The present review article is aimed to provide a detailed outline of the fundamental causes and the surprising relationship of inflammation in the onset of sundry diseases or illnesses. Furthermore, the role of various anti-inflammatory drugs alone and in combination with other therapeutic drugs, in alleviating the life-threatening diseases has also been discussed.

Background: CD28, a cell surface glycoprotein receptor, predominantly expressed on activated T cells, belongs to the Ig superfamily and provides a critical co-stimulatory signal. CTLA-4 has sequence homology to CD28, and is expressed on T cells after activation. It provides an inhibition signal coordinated with CD28 to regulate T cell activation. Both of them regulate T cell proliferation and differentiation and play an important role in the immune response pathway in vivo. Objective: We studied the special role of different structural sites of CD28 in producing costimulatory signals. Methods: We reviewed the relevant literature, mainly regarding the structure of CD28 to clarify its biological function, and its role in the immune response. Results: In recent years, increasingly attention has been paid to CD28, which is considered as a key therapeutic target for many modern diseases, especially some immune diseases. Conclusion: In this paper, we mainly introduce the structure of CD28 and its related biological functions, as well as the application of costimulatory pathways targeting CD28 in disease treatment.

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

Clozapine has been regarded as the last-line antipsychotic agent for patients with refractory schizophrenia. However, many patients remain unresponsive to clozapine, referred to as “clozapineresistant”, “ultra-treatment-resistant”, or remain in incurable state. There has been no convincing evidence for augmentation on clozapine so far. Novel treatments including numerous N-methyl-Daspartate (NMDA) receptor (NMDAR) enhancers, such as glycine, D-serine, D-cycloserine, and Nmethylglycine (sarcosine) failed in clinical trials. Earlier, the inhibition of D-amino acid oxidase (DAAO) that may metabolize D-amino acids and activate NMDAR has been reported to be beneficial for patients with schizophrenia receiving antipsychotics except for clozapine. A recent randomized, double-blind, placebo-controlled clinical trial found that add-on sodium benzoate, a DAAO inhibitor, improved the clinical symptoms in patients with clozapine- resistant schizophrenia, possibly through DAAO inhibition (and thereby NMDAR activation) and antioxidation as well; additionally, sodium benzoate showed no obvious side effects, indicating that the treatment is safe at doses up to 2 g per day for 6 weeks. More studies are warranted to elucidate the mechanisms of sodium benzoate for the treatment of schizophrenia and the etiology of this severe brain disease. If the finding can be reconfirmed, this approach may bring new hope for the treatment of the most refractory schizophrenia. This review summarizes the current status of clinical trials and related mechanisms for treatmentresistant, especially, clozapine-resistant schizophrenia. The importance of understanding the molecular circuit switches is also highlighted which can restore brain function in patients with schizophrenia. Future directions in developing better treatments for the most difficult to cure schizophrenia are also discussed.

Introduction: Tumor cells may present several molecular alterations that favor their malignancy, among which there is the expression of tumor-related antigens, such as truncated T-glycans, Thomsen-nouvelle, sialyl-Lewis X and sialyl Tn, which may help in the diagnosis and treatment using specific target molecules. Lectins are ubiquitous proteins capable of interacting with specific carbohydrates. Lectins isolated from marine organisms have important characteristics such as low immunogenicity and can bind to complex glycans compared to plant lectins. Objective: This work evaluated, through a systematic review, the molecular mechanisms of antitumor activity of lectins isolated from marine organisms. Methodology: The Pubmed, Lilacs, Science Direct, Wiley and Scopus databases were reviewed using the descriptors: marine lectin and cancer. Articles in English, published between January 2008 and December 2018, which proposed the molecular mechanisms of anticancer activity of lectins from marine organisms were eligible for the study. Results: 17 articles were eligible. The lectins showed promising performance against cancer cells, presenting specific cytotoxicity for some types of malignant cells. The articles presented several lectins specific to different carbohydrates, modulating: pro and anti-apoptotic proteins, transcription factor E2F-1, via mitogen-activated protein kinase. In addition, exogenous lectin expression in cancer cells has been shown to be a promising way to treat cancer. Conclusion: This review showed the various studies that described the molecular mechanisms caused by marine lectins with antineoplastic potential. This knowledge is relevant for the development and use of the next generations of lectins isolated from marine organisms, supporting their potential in cancer treatment.