scholarly journals When Leptin Is Not There: A Review of What Nonsyndromic Monogenic Obesity Cases Tell Us and the Benefits of Exogenous Leptin

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaio Cezar Rodrigues Salum ◽  
Jônatas de Mendonça Rolando ◽  
Verônica Marques Zembrzuski ◽  
João Regis Ivar Carneiro ◽  
Cicero Brasileiro Mello ◽  
...  

Obesity is a pandemic condition of complex etiology, resulting from the increasing exposition to obesogenic environmental factors combined with genetic susceptibility. In the past two decades, advances in genetic research identified variants of the leptin-melanocortin pathway coding for genes, which are related to the potentiation of satiety and hunger, immune system, and fertility. Here, we review cases of congenital leptin deficiency and the possible beneficial effects of leptin replacement therapy. In summary, the cases presented here show clinical phenotypes of disrupted bodily energy homeostasis, biochemical and hormonal disorders, and abnormal immune response. Some phenotypes can be partially reversed by exogenous administration of leptin. With this review, we aim to contribute to the understanding of leptin gene mutations as targets for obesity diagnostics and treatment strategies.

2006 ◽  
Vol 3 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Aristo Vojdani ◽  
Jonathan Erde

Over the past decade, great interest has been given to regulatory T (Treg) cells. A vast body of evidence has shown the existence and highlighted the importance of Treg cells in the active suppression of immune system responses. This form of immunoregulation is the dominant means utilized by the immune system to reach a harmony between reciprocal response processes in order to ensure adequate host defense with minimal host detriment. Therapeutically targeting Treg cells is a direct and powerful means to manipulate the immune system to achieve beneficial effects on various disease pathologies, including allergy, autoimmunity and cancer, as well as the facilitation of organ transplantation. This powerful target for immunoregulation is of much concern to practitioners and researchers of complementary and alternative medicine because it allows a great deal of control and certainty in dealing with the prevalence of debilitating immune system-related disorders for which there has been little remedy outside of Western Medicine.


Author(s):  
Elvan Dwi Widyadi ◽  
Yetti Hernaningsih ◽  
Endang Retnowati ◽  
Ugroseno Ugroseno ◽  
Ryzky Widi Atmaja

Acute Mieloid Leukemia (AML) is a hematologic cause of cancer deaths of 1.2% including a relatively rare disease but by the end of the decade there is an increase in the number of new cases. The immune system in AML is caused by gene mutations giving immunosuppressive effects so that the immune system will be inhibited in eliminating leukemia cells. The immune response of tumors is important to determine the prognosis, development of new cancer immunotherapy as well. One of the subset of lymphocytes T is  gdT lymphocyte cell with innate nature, but until now no information is required about gdT cell profile in AML patients. gdT cells have properties as antitumors played by Interferon production g (INF g), and the nature of protumor by interleukin 17 (IL-17). The percentage of lymphocyte T (CD3 +) of AML patients and healthy people did not differ (p = 0.528), indicating, not being activated for proliferation. gdT Lymphocyte cells percentage in healthy people by race, genetic and exposure to the surrounding environment such as infection. Percentage of gdT lymphocyte of AML patients and healthy people was not different from (p = 0.694), showed an immune response by gdT cells Unefected to proliferate. The percentage of gdT llimfocytes expressing the interleukin 17 (gdT17 cells)in patients AML and healthy people did not differ significantly (p = 0.436), this indicates inhibited proliferation.


2019 ◽  
Vol 19 (19) ◽  
pp. 1611-1626 ◽  
Author(s):  
Xiang-Li Bai ◽  
Xiu-Ling Deng ◽  
Guang-Jie Wu ◽  
Wen-Jing Li ◽  
Si Jin

Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.


2021 ◽  
Author(s):  
Xiaonan Sheng ◽  
Huijuan Dai ◽  
Yonggang Song ◽  
Xueyun Ma

Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it lacks an efficient target treatment. Here, we aimed to gain knowledge on the development of TNBC research and explore potential treatment strategies.Methods: We analyzed 14,389 publications on TNBC from the Web of Science (WOS) over the past 20 years, from 2000 to 2020, using bibliometric methods. We evaluated the publication tendency of TNBC and the contributions of different countries. Institutions and journals with the highest number of TNBC publications were screened. Finally, the research focus of the TNBC publications were also analyzed.Results: TNBC publications have significantly increased in the past 20 years, with elevated relative research interest (RRI). The USA has the most TNBC-related publications with high quality, and China is the country with the most rapid growth tendency in TNBC publications. The University of Texas System is the institution with the most TNBC publications. Breast Cancer Research and Treatment is the journal that published the most TNBC-related publications. The top 30 publications with high citations are also listed. The researches focusing on TNBC in the past 20 years were separated into four main clusters: tumor biology, TNBC therapies, treatment sensitivity, and gene mutations. The research focus in TNBC ranked by appearing years reflects the development of TNBC treatment strategy, showing that targeting tumor immunity is now the main focus in TNBC research. Conclusions: Using bibliometric analysis, we initially revealed the increasing interest in TNBC research and summarized the publication tendency of TNBC. We also reported focused topics screened from publications in the past 20 years, indicating the main problems and research objectives of TNBC for the first time. Immune-related topics are becoming the focus of TNBC research.


2019 ◽  
Vol 74 (2) ◽  
pp. 115-124 ◽  
Author(s):  
Carolina Maldonado Galdeano ◽  
Silvia Inés Cazorla ◽  
José María Lemme Dumit ◽  
Eva Vélez ◽  
Gabriela Perdigón

Background: The gastrointestinal tract is one of the most microbiologically active ecosystems that plays a crucial role in the working of the mucosal immune system (MIS). In this ecosystem, the consumed probiotics stimulate the immune system and induce a network of signals mediated by the whole bacteria or their cell wall structure. This review is aimed at describing the immunological mechanisms of probiotics and their beneficial effects on the host. Summary: Once administered, oral probiotic bacteria interact with the intestinal epithelial cells (IECs) or immune cells associated with the lamina propria, through Toll-like receptors, and induce the production of different cytokines or chemokines. Macrophage chemoattractant protein 1, produced by the IECs, sends signals to other immune cells leading to the activation of the MIS, characterized by an increase in immunoglobulin A+ cells of the intestine, bronchus and mammary glands, and the activation of T cells. Specifically, probiotics activate regulatory T cells that release IL-10. Interestingly, probiotics reinforce the intestinal barrier by an increase of the mucins, the tight junction proteins and the Goblet and Paneth cells. Another proposed mechanism of probiotics is the modulation of intestinal microbiota by maintaining the balance and suppressing the growth of potential pathogenic bacteria in the gut. Furthermore, it has been demonstrated that long-term probiotics consumption does not affect the intestinal homeostasis. The viability of probiotics is crucial in the interaction with IECs and macrophages favoring, mainly, the innate immune response. Macrophages and Dendritic cells (DCs) play an important role in this immune response without inducing an inflammatory pattern, just a slight increase in the cellularity of the lamina propria. Besides, as part of the machinery that probiotics activate to protect against different pathogens, an increase in the microbicidal activity of peritoneal and spleen macrophages has been reported. In malnutrition models, such as undernourishment and obesity, probiotic was able to increase the intestinal and systemic immune response. Furthermore, probiotics contribute to recover the histology of both the intestine and the thymus damaged in these conditions. Probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. Different mechanisms such as the generation of cytokines from activated pro-T-helper type 1, which favor the production of IgG instead of IgE, have been proposed. Key Messages: Probiotic bacteria, their cell walls or probiotic fermented milk have significant effects on the functionality of the mucosal and systemic immune systems through the activation of multiple immune mechanisms.


2011 ◽  
Vol 2 (2) ◽  
pp. 173
Author(s):  
Nikos G. Gavalas ◽  
Meletios A. Dimopoulos ◽  
Aristotelis Bamias

Ovarian cancer is one of the leading causes of cancer-related death among women. Disease relapse occurs in a high number of cases and treatment currently involves the use of chemotherapy with the use of paclitaxel and platinum-based agents. Resistance to the disease occurs in more than 70% of the cases. The immune system is increasingly becoming a target for intense research in order to study the host’s immune response against ovarian cancer. T cell populations, including NK T cells and Tregs, have been associated with disease outcome indicating their increasing clinical significance, having been associated with positive prognosis and as markers of disease progress, respectively. Cytokines may also be associated with positive prognosis and they can have a direct or indirect effect in mobilizing relevant T cells, thus eliciting an immune response. Harnessing the immune system capacity in order to induce anti-tumor response is a major challenge. This is achieved via the use of antibodies that can elicit an immune response or via the use of direct administration of cytotoxic T cell populations (e.g., CD8?). This review examines the recent developments in our understanding of the mechanisms of development of the immune response in ovarian cancer as well as its prognostic significance and the existing experience in clinical studies using factors associated with immune response, such as monoclonal antibodies, cytokines, vaccines and activated or expanded relevant autologous populations from peripheral blood.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 468
Author(s):  
Antonella Di Sotto ◽  
Annabella Vitalone ◽  
Silvia Di Giacomo

Immunomodulators are agents able to affect the immune system, by boosting the immune defences to improve the body reaction against infectious or exogenous injuries, or suppressing the abnormal immune response occurring in immune disorders. Moreover, immunoadjuvants can support immune system acting on nonimmune targets, thus improving the immune response. The modulation of inflammatory pathways and microbiome can also contribute to control the immune function. Some plant-based nutraceuticals have been studied as possible immunomodulating agents due to their multiple and pleiotropic effects. Being usually more tolerable than pharmacological treatments, their adjuvant contribution is approached as a desirable nutraceutical strategy. In the present review, the up to date knowledge about the immunomodulating properties of polysaccharides, fatty acids and labdane diterpenes have been analyzed, in order to give scientific basic and clinical evidence to support their practical use. Since promising evidence in preclinical studies, limited and sometimes confusing results have been highlighted in clinical trials, likely due to low methodological quality and lacking standardization. More investigations of high quality and specificity are required to describe in depth the usefulness of these plant-derived nutraceuticals in the immune system modulation, for health promoting and disease preventing purposes.


Parasitology ◽  
2009 ◽  
Vol 136 (6) ◽  
pp. 627-639 ◽  
Author(s):  
M. E. SOLANA ◽  
C. D. ALBA SOTO ◽  
M. C. FERNÁNDEZ ◽  
C. V. PONCINI ◽  
M. POSTAN ◽  
...  

SUMMARYInfection with a myotropicTrypanosoma cruziclone induces maternal fertility failure. In the current work, we evaluated whether reduction of maternal parasitaemia before mating has beneficial effects on pregnancy outcome. Female mice were subjected to benznidazole (Bz) treatment after infection. On day 30 of therapy, mating was assessed and pregnancy outcome was determined on day 14 of gestation. Fetal resorptions diminished inT. cruzi-infected Bz-treated mice compared withT. cruzi-infected untreated mice. This was in agreement with the reduction in the blood/solid tissue parasite load and with the percentage of necrotic foci in placental samples fromT. cruzi-infected Bz-treated females. To study eventual changes in the immune homeostasis ofT. cruzi-infected Bz-treated mice, activation of the immune system was evaluated at the end of Bz therapy and before mating. We found specific IgG1reduction resulting in a predominance of specific IgG2a, reduced numbers of CD69+CD4+cells and diminished frequency and numbers of CD44+T cells. Concanavalin A-stimulated splenocytes fromT. cruzi-infected Bz-treated mice produced higher amounts of IFN-γ thanT. cruzi-infected untreated mice. These results indicate that reduction of maternal parasite load improves pregnancy outcome. These findings correlate with a favourable modulation of the immune response.


2021 ◽  
Vol 68 (2) ◽  
pp. 147-153
Author(s):  
Ana Maria Chivu ◽  
◽  
Elena Bălășescu ◽  
Roxana Ioana Nedelcu ◽  
Alice Brînzea ◽  
...  

The pathogenesis of vitiligo is still unclear. The complexity of the disease seems to be based on the intervention of environmental factors in the background of genetic predisposition which will determine the response of the immune system, the involvement of the nervous and endocrine systems, altered metabolisms and increased oxidative stress - all these elements leading to melanocytic dysfunction and their subsequent destruction. Melanocytic death has a clinical correspondent that embraces the form of white macules on the skin, associated or not with leucotrichia. A better understanding of vitiligo' s pathophysiology and mechanisms of cell death at the skin level can be a step to some appropriate treatment strategies.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jessica M. F. Hall ◽  
desAnges Cruser ◽  
Alan Podawiltz ◽  
Diana I. Mummert ◽  
Harlan Jones ◽  
...  

Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.


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