Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model.

The excretory-secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30-150-nm-sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto-lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV-treated macrophages. Due to this, both macro-autophagy and caspase-linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT-mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV-mediated immune suppression revealed that the EV can protect the mice from DSS-induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.

Immunoinformatics Approaches for Vaccine Design: A Fast and Secure Strategy for Successful Vaccine Development.

Vaccines are major contributors to the cost-effective interventions in major infectious diseases in the global public health space [...].

Wear rate and biocompatibility of pre and post UV irradiated UHMWPE for tribo-pair in total knee replacement application.

Ultra-high molecular weight polyethylene (UHMWPE) and CoCr alloy are popular tribo-pair in total knee replacement. Wear in the liner is a major failure reason for knee implant. Therefore, this work focuses on an approach for reducing the wear rate by irradiating the UHMWPE specimens using Ultraviolet (UV) radiation. The powder of UHMWPE was molded into a plate by microwave-assisted compression (MAC) molding. The UV radiations of intensity 0.025 J/cm2 were irradiated on the MAC molded UHMWPE specimens. The wear rate was determined using a pin on the disc wear tribometer using the pre and post-irradiated UHMWPE specimens as a pin and CoCr alloy as the disc. The pre and post-irradiated UHMWPE sliding was done at the load of 40 N for 1500 m under dry conditions. The reduction in the wear rate recorded was 56% after UV irradiation. The surface morphology of the worn specimens was done using scanning electron microscopy (SEM) and the 3D surface mapping technique. The obtained results of wear rate were validated numerically by implementing the contact problem solution in Archard's wear law using user-subroutine on Python. The experimental and numerically obtained results were in good agreement. The biological response of pre and post-irradiated specimens was evaluated by hemolysis assay, cellular compatibility against peripheral blood mononuclear cells, platelet adhesion, and in vitro degradation under a simulated blood fluid environment.

Immunoinformatics driven construction of multi-epitope vaccine candidate against Ascaris lumbricoides using its entire immunogenic epitopes.

OBJECTIVE: Ascaris lumbricoides infects 80 million people per year, causing malnutrition, stunted growth of children etc., but there is no vaccine available against it. We aimed to design a multimeric-subunit vaccine using comprehensive immunoinformatic approach. RESEARCH DESIGN AND METHODS: The T and B cell epitopes were shortlisted on antigenicity, allergenicity, and toxicity from proteome data and joined with appropriate linkers. The physical characteristics of vaccine candidate was calculated and docking/molecular dynamic simulation performed to validate its robustness. The multimeric protein was codon optimized and in-silico cloned in pET28b. RESULTS: From the 23,604 proteins of Ascaris, we filtered based on epitope prediction, localization, antigenicity, and allergenicity. Prepared a vaccine of 534 amino acid long, 56.31 kD weight and pI 4.52. Physiochemical features showed it is soluble, highly antigenic and non-allergenic. Its tertiary structure was forecasted, certified, and refined. The immunoinformatic simulation studies showed it to be potent T and B cell stimulator. CONCLUSIONS: We identified highly antigenic peptides of Ascaris from its proteome with good potential to induce innate as well as humoral immune response. These peptides were used to design a chimeric vaccine against Ascariasis infection, which can be used for prophylactic purpose but needs experimental and clinical validation.

Vaccine for a neglected tropical disease Taenia solium cysticercosis: fight for eradication against all odds.

INTRODUCTION: Taenia solium infection is among the 17 most neglected tropical diseases identified by World Health Organization and to be eradicated by 2030. This parasite infects the central nervous system (Neurocysticercosis [NCC]) and intestine [Taeniasis]). NCC is the most frequent cause of acquired epilepsy in endemic regions and Taeniasis is responsible for the widespread malnutrition and abdominal discomfort among children. Epilepsy caused by T. solium is preventable and the total elimination of NCC can be achieved by good hygiene, mass therapy, and most importantly vaccination of pigs or humans. Vaccine for pig is available but not widely in use and for humans it's still elusive. AREA COVERED: Several vaccine candidates for porcine cysticercosis have been tried like TSOL18, SP3Vac, KETc7, TSOL45, etc. with good success in the limited field trial. This review highlights some seminal contributions for the anti-cestode vaccine, the associated challenges, current status, suggestive future directions, and the need of vaccine for human use. EXPERT OPINION: Though several vaccines are available, none is being widely used due to lack of awareness, economic constraints, accessibility, etc. Hence, there is a need for a newer, economic, and reliable vaccine for humans or pigs use to reduce the disease burden.