Vol 3-3 Commentary

Neuroimmune Imbalance: The Key for the Treatment of Anxiety?

Bai Li, Tangxin Gao, Jing Du *

School of Medicine, Yunnan University, 2 Cuihu North Road, Kunming, 650091, Yunnan, China

DOI: 10.29245/2578-3009/2019/3.1175 View / Download Pdf
Vol 3-3 Mini Review

Synaptic Compensatory Mechanism and its Impairment in Autoimmune Myasthenic Diseases

Masaharu Takamori*

Neurological Center, Kanazawa-Nishi Hospital, Kanazawa, Ishikawa, 920-0025, Japan

The neuromuscular junction (NMJ) is organized by a complex architecture and various signals orchestrated by sophisticated interactions. They include the presynaptic Ca2+ homeostasis for acetylcholine (ACh) release in the active zone organization, the post-synaptic ACh receptor (AChR) clustering at endplate membranes, the trans-synaptic communication from muscle to nerve, and the synaptic stabilization. The present data and discussions are concerned in an adaptive change of ACh release from the nerve terminal and its immunological impairment in the post-synaptic disease (myasthenia gravis, MG) and the presynaptic disease (Lambert-Eaton myasthenic syndrome, LEMS).?Discussions mainly focus the antibody-induced failure of the synaptic compensatory mechanisms that are brought about by the presynaptic autoreceptors (the M1-type muscarinic AChR [mAChR] cooperated with adenosine receptors), and the non-voltage-gated Ca2+-dominant influx channel (transient receptor potential canonical [TRPCs], particularly its phenotype TRPC3). Besides the synaptic transmission fatigue, the TRPC3 antibodies are discussed in terms of their implication in the muscle contraction fatigue that often occurs in the thymoma-associated MG and reflects a defect in the physiological association of TRPC3 with the ryanodine receptor-1 in the excitation-contraction coupling in which the sarcoplasmic Ca2+ release takes place. In addition to the modulating role in the NMJ functions, the mAChRs participate in the innate and adaptive inmmunity by MG thymus and in the lung cancer (often associated with LEMS) growth.

DOI: 10.29245/2578-3009/2019/3.1173 View / Download Pdf
Vol 3-3 Review Article

Immunometabolic Links Underlying the Infectobesity with Persistent Viral Infections

Yongming Sang*

Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN, USA

Obesity and its related comorbidities are prevailing globally. Multiple factors are etiological to cause obesity and relevant metabolic disorders. In this regard, some pathogenic infections including those by viruses have also been associated with obesity (termed as infectobesity). In this mini-review, I examined recent publications about primary or cofactorial role of viral infections to exacerbate the local and systemic immunometabolic cues that underlie most cofactorial obesity. Major immuno-metabolic pathways involved, including that mediated by interferon (IFN) signaling and peroxisome proliferator activated receptor-γ (PPAR-γ), are discussed.

DOI: 10.29245/2578-3009/2019/4.1176 View / Download Pdf
Vol 3-3

Association of Gender with Efficacy of Immunotherapy in Metastatic Melanoma

Varsha Jain1, Sriram Venigalla1, Kevin T. Nead1, Wei-Ting Hwang2, John N. Lukens1, Tara C. Mitchell3, Jacob E. Shabason1*

1Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

2Department of Biostatistics, Epidemiology and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

3Division of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Pre-clinical data from animal models suggest that the anti-tumor efficacy of immune checkpoint blockade agents may be influenced by gender specific sex hormones. However, recent meta-analyses of clinical data aimed at addressing the impact of gender on response to these agents have demonstrated conflicting results. Given the discordant evidence, we sought to evaluate the association of gender with the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. This retrospective cohort study used the National Cancer Database to identify patients who were ≥18 years old with Stage IV melanoma from 2011 to 2015. Patterns of utilization of immunotherapy, including by gender, were assessed using multivariable logistic regression. A multivariable Cox proportional hazards model, including an interaction term between the receipt of immunotherapy and gender, was used to evaluate whether gender modified the association of receipt of immunotherapy with hazards of death. 11,944 patients met study inclusion criteria. Of these, 8,093 (68%) were males and 3,851 (32%) were females. 2,930 (25%) patients received immunotherapy while 9,014 (75%) did not. There was no statistically significant difference in the receipt of immunotherapy between males and females. On multivariable analysis, receipt of immunotherapy was associated with a survival benefit in both males and females. However, a statistically significant difference in efficacy of immunotherapy based on gender was not observed (pinteraction =0.422). Utilizing a real world cohort of patients derived from a national cancer registry, gender was not associated with differences in immunotherapy survival outcomes in patients with metastatic melanoma.

DOI: 10.29245/2578-3009/2019/4.1174 View / Download Pdf