A Review on Plant-Derived Immunomodulatory Agents: Hopes as an Alternative Medicine in the Management of Immune-Related Disorders

In humans, the immune system serves as a protective barrier against infection; however, when the immune system is out of balance, it can harm the host. Immunomodulators are chemicals or medications that have been employed in the clinic to treat an unbalanced immune response. The majority of immunological medicines in clinical use are cytotoxic. They harm the patient's quality of life by causing various side effects and being associated with higher production costs, longer lead times, and a high failure rate. Furthermore, obtaining single-compound chemicals with low toxicity, high efficacy, and selectivity for specified disorders is difficult for researchers. As a result, techniques based on alternative medicine are gaining traction in drug development, focusing on innovative natural compounds utilized to treat various disorders. Many plant molecules founded to have biologically beneficial properties. This review aimed to look at the immunomodulatory activity of plant-derived chemicals from widely used plants that treat a range of diseases worldwide

Eradication of large solid tumors by gene therapy with a T cell receptor targeting a single cancer-specific point mutation

PURPOSE: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic non-synonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T cell receptor (TCR) that is specific for a single AAS. EXPERIMENTAL DESIGN: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. RESULTS: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intra-tumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. CONCLUSIONS: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape

Preclinical formulation for the pharmacokinetics and efficacy of GBO-006, a selective polo like kinase 2 (PLK2) inhibitor for the treatment of triple negative breast cancer

GBO-006 was shown to be a highly specific and selective PLK2 inhibitor that promoted mitotic arrest in various cancer cell lines, subsequently resulting in their apoptotic death. Intraperitoneal alternate day dosing of GBO-006 using 100 % DMSO as formulation showed significant tumor regression in xenograft models, demonstrating proof of concept of PLK2 inhibition in vivo. These studies necessitated the development of a suitable and GRAS (generally considered as safe) preformulation for pharmacokinetic and efficacy studies. GBO-006 possesses challenging physicochemical and biopharmaceutical properties like poor solubility in aqueous media, low permeability and a crystalline nature. Different methods like cosolvency, complexation and micellar solubilization were employed to improve the solubility of GBO-006. A strategy of co-solvency is used to solubilize the GBO-006 up to 10 mg/mL. A formulation with 20 % DMSO, 40 % PEG 400, 30 % of 100 mM citrate buffer (pH 3.0) and 10 % solutol displayed clear solution without any visual precipitation of the drug even after 2 weeks of storage. GBO-006 showed moderate clearance in rat and high systemic clearance in mouse and dog. It showed poor oral bioavailability across all species. Intraperitoneal dosing of GBO-006 demonstrated the linear exposure. GBO-006 showed significant inhibition of tumor progression

Deploying swarm intelligence in medical imaging identifying metastasis, micro-calcifications and brain image segmentation

This paper proposes an umbrella deployment of swarm intelligence algorithm such as Stochastic Diffusion Search for medical imaging applications. After summarising the results of some previous work which shows how the algorithm assists in the identification of metastasis in bone scans and microcalcifications on mammographs, for the first time, the use of the algorithm in assessing the CT images of aorta is demonstrated along with its performance in detecting the nasogastric tube in chest X-ray. The swarm intelligence algorithm presented in this paper is adapted to address these particular tasks and its functionality is investigated by running the swarms on sample CT images and X-rays whose status have been determined by senior radiologists. Additionally, a hybrid swarm intelligence-Learning Vector Quantisation (LVQ) approach is proposed in the context of Magnetic Resonance (MR) brain image segmentation. The Particle Swarm Optimisation (PSO) is used to train the LVQ which eliminates the iteration- dependent nature of LVQ. The proposed methodology is used to detect the tumour regions in the abnormal MR brain images

Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients

<p>Abstract</p> <p>Background</p> <p>Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis.</p> <p>Methods/Design</p> <p>This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews.</p> <p>Discussion</p> <p>This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.</p

Disturbances in Body Ownership in Schizophrenia: Evidence from the Rubber Hand Illusion and Case Study of a Spontaneous Out-of-Body Experience

A weakened sense of self may contribute to psychotic experiences. Body ownership, one component of self-awareness, can be studied with the rubber hand illusion (RHI). Watching a rubber hand being stroked while one's unseen hand is stroked synchronously can lead to a sense of ownership over the rubber hand, a shift in perceived position of the real hand, and a limb-specific drop in stimulated hand temperature. We aimed to assess the RHI in schizophrenia using quantifiable measures: proprioceptive drift and stimulation-dependent changes in hand temperature.The RHI was elicited in 24 schizophrenia patients and 21 matched controls by placing their unseen hand adjacent to a visible rubber hand and brushing real and rubber hands synchronously or asynchronously. Perceived finger location was measured before and after stimulation. Hand temperature was taken before and during stimulation. Subjective strength of the illusion was assessed by a questionnaire.Across groups, the RHI was stronger during synchronous stimulation, indicated by self-report and proprioceptive drift. Patients reported a stronger RHI than controls. Self-reported strength of RHI was associated with schizotypy in controls Proprioceptive drift was larger in patients, but only following synchronous stimulation. Further, we observed stimulation-dependent changes in skin temperature. During right hand stimulation, temperature dropped in the stimulated hand and rose in the unstimulated hand. Interestingly, induction of RHI led to an out-of-body experience in one patient, linking body disownership and psychotic experiences.The RHI is quantitatively and qualitatively stronger in schizophrenia. These findings suggest that patients have a more flexible body representation and weakened sense of self, and potentially indicate abnormalities in temporo-parietal networks implicated in body ownership. Further, results suggest that these body ownership disturbances might be at the heart of a subset of the pathognomonic delusions of passivity

Immunogenicity and Efficacy of Single Antigen Gp63, Polytope and PolytopeHSP70 DNA Vaccines against Visceral Leishmaniasis in Experimental Mouse Model

Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-γ over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis

Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection

Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems