Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer

Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.

Disrupted regulatory T cell homeostasis in inflammatorybowel diseases

In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells(Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases(IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20^(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.

Development of NK cell-based cancer immunotherapies through receptor engineering

Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.

Cell therapy for the treatment of reproductive diseases and infertility:an overview from the mechanism to the clinic alongside diagnostic methods

Infertility is experienced by 8%–12%of adults in their reproductive period globally and has become a prevalent concern.Besides routine therapeutic methods,stem cells are rapidly being examined as viable alternative therapies in regenerative medicine and translational investigation.Remarkable progress has been made in understanding the biology and purpose of stem cells.The affected pluripotent stem cells(iPSCs)and mesenchymal stem cells(MSCs)are further studied for their possible use in reproductive medicine,particularly for infertility induced by premature ovarian insufficiency and azoospermia.Accordingly,this study discusses current developments in the use of some kinds of MSCs such as adipose-derived stem cells,bone marrow stromal cells,umbilical cord MSCs,and menstrual blood MSCs.These methods have been used to manage ovarian and uterine disorders,and each technique presents a novel method for the therapy of infertility.

Expert group syndrome at high altitude

During a training session for the university diploma of Mountain medicine delivered by University Sorbonne Paris Nord for medical doctors,one of the participants developed signs of maladaptation to high altitude at 3600 m,the severity of which was incorrectly interpreted.Information was sparingly given by the patient(an anesthetist)to several of his colleagues and no one was in charge to collect clinical data,take a history,and provide appropriate treatment.The combination of the absence of designation of a supervising doctor and the difficulty of communicating with the patient led to a lack of coordinated management and to an evolution of the symptoms towards severe acute mountain sickness.Fortunately,the very rapid management of the patient and a rapid helicopter evacuation,as soon as the symptoms worsened towards the onset of a suspected high altitude cerebral and/or pulmonary edema,allowed rapid resolution without sequelae.Environmental,medical,psychological,and managerial factors led to this Expert Group Syndrome.