Combining Killed Vaccine Candidate with Different Adjuvants to Determine Prophylactic Potential against Leishmaniasis.

Visceral Leishmaniasis is a serious public health problem caused by Leishmania species parasites. Approximately 500 thousand people get Visceral Leishmaniasis (VL) every year. An effective and reliable vaccine against the disease has still not been formulated. Choosing the right adjuvant is important to increase immunogenicity in vaccines prepared with total antigens. In this study, we investigate the ideal adjuvant for use in vaccine formulations against VL. For this purpose, Leishmania antigens (FTLA) obtained from L. infantum parasites by the freeze-thaw method and three different adjuvants (alum-saponin and calcium phosphate) were used. The effectiveness of the formulations was investigated in vitro by cell viability analysis and determination of nitric oxide and cytokine production abilities in J774 macrophage cells. According to the study results, it was determined that formulations prepared with calcium phosphate produced 72% more NO and approximately 7.2 times more IL-12 cytokine. The results obtained showed that calcium phosphate salts can be used as ideal adjuvants in vaccine research against leishmaniasis.

Design and Simulation of the Microcantilever Biosensor for MITF Antigen and D5 Monoclonal Antibody Interaction Finite Element Analysis, and Experimental.

BACKGROUND: Biosensors and MEMS have witnessed rapid development and enormous interest over the past decades. Constant advancement in diagnostic, medical, and chemical applications has been demonstrated in several platforms and tools. In this study, the analytical and FEA of the microcantilever used in biomolecular analyses were compared with the experimental analysis results. METHODS: In this study, MITF antigen, which is a melanoma biomarker, and anti-MITF antibody (D5) were selected as biomolecules. A MEMS-type microcantilever biosensor was designed by functionalizing the AFM cantilever by utilizing the specific interaction dynamics and intermolecular binding ability between both molecules. Surface functionalization of cantilever micro biosensors was performed by using FEA. The stress that will occur as a result of the interactions between the MITF-D5 has been determined from the deviation in the resonant frequency of the cantilever. RESULTS: It has been found that the simulation results are supported by analytical calculations and experimental results. CONCLUSION: The fact that the results of the simulation study overlap with the experimental and mathematical results allows us to get much cheaper and faster answers compared to expensive and time-consuming experimental approaches.

Applications of Exosome Vesicles in Different Cancer Types as Biomarkers.

One of the biggest challenges in the fight against cancer is early detection. Early diagnosis is vital, but there are some barriers such as economic, cultural, and personal factors. Considering the disadvantages of radiological imaging techniques or serological analysis methods used in cancer diagnosis, such as being expensive, requiring expertise, and being time-consuming, there is a need to develop faster, more reliable, and cost-effective diagnostic methods for use in cancer diagnosis. Exosomes, which are responsible for intercellular communication with sizes ranging from 30-120 nm, are naturally produced biological nanoparticles. Thanks to the cargo contents they carry, they are a potential biomarker to be used in the diagnosis of cancer. Exosomes, defined as extracellular vesicles of endosomal origin, are effective in cancer growth, progression, metastasis, and drug resistance, and changes in microenvironmental conditions during tumor development change exosome secretion. Due to their high cellular activity, tumor cells produce much higher exosomes than healthy cells. Therefore, it is known that the number of exosomes in body fluids is significantly rich compared to other cells and can act as a stand-alone diagnostic biomarker. Cancer- derived exosomes have received great attention in recent years for the early detection of cancer and the evaluation of therapeutic response. In this article, the content, properties, and differences of exosomes detected in common types of cancer (lung, liver, pancreas, ovaries, breast, colorectal), which are the leading causes of cancer-related deaths, are reviewed. We also discuss the potential utility of exosome contents as a biomarker for early detection, which is known to be important in targeted cancer therapy.

Particulate and non-particle adjuvants in Leishmaniasis vaccine designs: A review.

Leishmaniasis is a parasitic disease with different clinical forms caused by protozoan parasites of the genus Leishmania and transmitted by the bite of an infected female sandfly. According to the World Health Organization (WHO), it is the second most common parasitic disease after malaria and it is known that approximately 350 million people are at risk. The disease manifests itself in different clinical forms. In addition to asymptomatic cases, cutaneous leishmaniasis (CL), which creates large lesions on the skin, and visceral leishmaniasis (VL), which causes death if not treated, especially affecting the abdominal organs, are two important clinical forms. When the studies were examined, it was seen that a clinically used vaccine against any form of human leishmaniasis has not been developed yet. In some studies, it was stated that the lack of appropriate adjuvant was responsible for the failure to develop an effective Leishmania vaccine. We can say that strong adjuvants are needed to achieve successful vaccines. In this article, adjuvants and adjuvant candidates used in vaccine studies against leishmaniasis are discussed.

The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches.

mTOR is a serine/threonine kinase that plays various roles in cell growth, proliferation, and metabolism. mTOR signaling in cancer becomes irregular. Therefore, drugs targeting mTOR have been developed. Although mTOR inhibitors rapamycin and rapamycin rapalogs (everolimus, rapamycin, temsirolimus, deforolimus, etc.) and new generation mTOR inhibitors (Rapalink, Dual PI3K/mTOR inhibitors, etc.) are used in cancer treatments, mTOR resistance mechanisms may inhibit the efficacy of these drugs. Therefore, new inhibition approaches are developed. Although these new inhibition approaches have not been widely investigated in cancer treatment, the use of nanoparticles has been evaluated as a new treatment option in a few types of cancer. This review outlines the functions of mTOR in the cancer process, its resistance mechanisms, and the efficiency of mTOR inhibitors in cancer treatment. Furthermore, it discusses the next-generation mTOR inhibitors and inhibition strategies created using nanoparticles. Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in cancer treatments, new inhibition strategies should be developed. Inhibition approaches are created using nanoparticles, and one of them offers a promising treatment option with evidence supporting its effectiveness.

Regenerative Therapy Approaches and Encountered Problems in Sensorineural Hearing Loss.

Hearing loss is one of the most important public health matters worldwide, severely affecting people's social, psychological, and cognitive development. The perception of sound, movement, and balance in vertebrates depends on a special sensory organ called the cochlea, which contains hair cells and supporting cells in the inner ear. Genetic factors, epigenetics, the use of ototoxic drugs (some antibiotics and chemotherapeutics), noise, infections, or even aging can cause loss of hair cells and their related primary neurons, leading to sensorineural hearing loss. Although a sensorineural hearing loss, also known as permanent hearing loss, is treated with hearing aids and cochlear implants, treatment methods are limited. Since even the best implant cannot exhibit the characteristics of the original ear, the permanent sensory deficit will be permanent. For this reason, it has become important to develop regenerative treatment methods to regenerate and replace lost or damaged hair cells and neurons. Developments in stem cell technology have led to promising studies in regenerating damaged/lost hair cells or neurons with endogenous or exogenous cell-based therapies. Epigenetic mechanisms can turn hearing-related genes on and off and determine which proteins to copy. In addition, due to gene silencing, gene replacement, and CRISPR/CAS9 technology, gene therapy methods have accelerated, and studies have been carried out to treat dominant and recessive mutations that cause genetic-induced hearing loss or increase hair cell regeneration. In this paper, potential gene therapy and stem cell applications in the acquisition of cochlear function, which causes sensorineural hearing loss, and the difficulties encountered in these applications are compiled from a bioengineering perspective.

In Vitro Determination of Antileshmanial Activities of Benzimidazolium Derivatives on L. major Promastigotes and Amastigotes.

PURPOSE: Leishmaniasis is a serious public health problem infecting millions of people worldwide. An effective and reliable treatment method to be used in the treatment of the disease has not been developed yet. METHODS: In this article, the anti-leishmanial activities of two benzimidazolium derivatives (B.A and B.B) against Leishmania major promastigotes and amastigotes, which are known to cause cutaneous leishmaniasis, were investigated for the first time. The immunostimulatory activity of the developed formulations was determined using the J774 murine macrophage cell line. RESULTS: B.A and B.B compounds were found to have a much higher cytotoxic effect than Amphotericin B (IC50 value 0.75 µM ± 0.03), which is used as the reference drug. The IC50 value was determined as 2.02 µM ± 0.52 for B.A and 1.83 µM ± 0.71 for B.B in Leishmania promastigotes. In addition, IC50 values of B. A and B.B Leishmania amastigotes were found to be 1.01 µM and 0.67 µM, respectively. It was found that B.B was 81.12 times more selective than Amphotericin B and showed the highest selectivity against L. major promastigotes (359.09) and amastigotes (980.80). Considering the selectivity indices (SI) of B.A and B.B, both compounds tested are more promising than Amphotericin B. CONCLUSION: The results showed that benzimidazolium derivatives have anti-leishmanial potential against L. major, which is the causative agent of cutaneous leishmaniasis. Thus, we can say that the obtained results will help the development of effective and safe antileishmanial drug formulations against cutaneous leishmaniasis.