Physiological anti-inflammatory mechanisms are selected by evolution to effectively control the immune system and can be exploited for the treatment of inflammatory disorders. Recent studies indicate ...that the vagus nerve (which is the longest of the cranial nerves and innervates most of the peripheral organs) can modulate the immune response and control inflammation through a 'nicotinic anti-inflammatory pathway' dependent on the alpha7-nicotinic acetylcholine receptor (alpha7nAChR). Nicotine has been used in clinical trials for the treatment of ulcerative colitis, but its clinical applications are limited by its unspecific effects and subsequent toxicity. This article reviews recent advances supporting the therapeutic potential of selective nicotinic agonists in several diseases. Similar to the development of alpha- and beta-agonists for adrenoceptors, selective agonists for alpha7nAChR could represent a promising pharmacological strategy against infectious and inflammatory diseases.
The ability to perform movements is vital for our daily life. Our actions are embedded in a complex environment where we need to deal efficiently in the face of unforeseen events. Neural oscillations ...play an important role in basic sensorimotor processes related to the execution and preparation of movements. In this review, I will describe the state of the art regarding the role of motor gamma oscillations in the control of movements. Experimental evidence from electrophysiological studies has shown that motor gamma oscillations accomplish a range of functions in motor control beyond merely signaling the execution of movements. However, these additional aspects associated with motor gamma oscillation remain to be fully clarified. Future work on different spatial, temporal and spectral scales is required to further understand the implications of gamma oscillations in motor control.
Acetylcholine is a cellular mediator selected early in evolution as a key neu- rotransmitter, but its other biological roles including immune-modulation remain to be elucidated. In a recent paper ...published in Cell Research, Sun et aL report that acetylcholine modulates cytokine production in macrophages via microRNA-124.
Past research has yielded conflicting findings concerning socio-cognitive deficits in individuals with autistic traits. This raises the fundamental question whether autistic traits and ...socio-cognitive abilities are related. The present study investigated whether three key socio-cognitive abilities—imitation-inhibition, empathy, and emotion regulation—can serve as predictive factors for autistic traits within a neurotypical population. Participants (N = 166, Mage = 24.83 years, SDage = 5.20 years, rangeage = 18 to 39 years) were asked to perform an online imitation-inhibition task and complete self-report measures assessing empathy, emotion regulation, and autistic traits. Empathy was measured using the Interpersonal Reactivity Index (IRI), emotion regulation was assessed using the Difficulties in Emotion Regulation Scale (DERS), and autistic traits were measured using the ten-item short form of the Autism-Spectrum Quotient (AQ-10). Multiple regression analyses revealed that both imitation-inhibition and emotion regulation were significantly associated with autistic traits. However, empathy was not found to be a significant predictor. Our study aimed to clarify inconsistent results regarding the relationship between socio-cognitive abilities and autistic traits.
Neurons that express a specific molecular marker are activated by 'electroacupuncture' stimulation. They can then mediate the treatment's anti-inflammatory effects in a mouse model of the ...inflammatory condition sepsis.
Transgelin-2 has been regarded as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. However, transgelin-2 has recently been shown to relax the myosin cytoskeleton ...of the airway smooth muscle cells by acting as a receptor for extracellular metallothionein-2. From a clinical perspective, these results support transgelin-2 as a promising therapeutic target for diseases such as cancer and asthma. The inhibition of transgelin-2 prevents actin gelation and thereby cancer cell proliferation, invasion, and metastasis. Conversely, the activation of transgelin-2 with specific agonists relaxes airway smooth muscles and reduces pulmonary resistance in asthma. Here, we review new studies on the biochemical properties of transgelin-2 and discuss their clinical implications for the treatment of immune, oncogenic, and respiratory disorders.
Actin is a critical component of the cellular cytoskeleton and interacts with a plethora of actin-binding proteins.Transgelin-2 is an important actin-binding protein and misregulation of transgelin-2 may contribute to diseases such as cancer and asthma.Ezrin has emerged as an essential regulator of transgelin-2 in biological functions other than those involving actin.Specific targeting of transgelin-2 may result in a high potential to selectively and effectively regulate various diseases.
Classically, sympathetic and parasympathetic systems act in opposition to maintain the physiological homeostasis. In this article, we report that both systems work together to restrain systemic ...inflammation in life-threatening conditions such as sepsis. This study indicates that vagus nerve and cholinergic agonists activate the sympathetic noradrenergic splenic nerve to control systemic inflammation. Unlike adrenalectomy, splenectomy and splenic neurectomy prevent the anti-inflammatory potential of both the vagus nerve and cholinergic agonists, and abrogate their potential to induce splenic and plasma norepinephrine. Splenic nerve stimulation mimics vagal and cholinergic induction of norepinephrine and re-establishes neuromodulation in α7 nicotinic acetylcholine receptor (α7nAChR)-deficient animals. Thus, vagus nerve and cholinergic agonists inhibit systemic inflammation by activating the noradrenergic splenic nerve via the α7nAChR nicotinic receptors. α7nAChR represents a unique molecular link between the parasympathetic and sympathetic system to control inflammation.
This study describes the formation of indeterminate pronouns in Shawi, which is a class of proforms that can have interrogative, indefinite, and free relative senses. These interpretations are only ...distinguished through a class of clitics, e.g. ma'=ta (what, relative what), ma'=sha (something), ma=nta (nothing). The first of these can be further modified to ma'ta=ka (rhetorical what) and ma'=tana (whatever). As in other languages, this class of proforms can be categorized into a paradigm in which each member represents a general concept like person (who), thing (what), place (where), time (when), manner (how), etc. Comparing these forms reveals further internal structure. As such, Shawi indeterminate pronouns are analyzed and the clitics that can modify their interpretation are discussed.
•The vagus nerve controls inflammation and organ injury by regulating the production of inflammatory factors in the spleen.•Most studies showed absence of neurogenic cholinergic markers in the ...spleen.•Recent studies suggest that vagal regulation of inflammation is mediated by multi-synaptic interactions between the vagus and the splanchnic nerves.•These mechanisms are allowing the design of novel therapeutic strategies for infectious and inflammatory disorders.
The vagus nerve coordinates most physiologic functions including the cardiovascular and immune systems. This mechanism has significant clinical implications because electrical stimulation of the vagus nerve can control inflammation and organ injury in infectious and inflammatory disorders. The complex mechanisms that mediate vagal modulation of systemic inflammation are mainly regulated via the spleen. More specifically, vagal stimulation prevents organ injury and systemic inflammation by inhibiting the production of cytokines in the spleen. However, the neuronal regulation of the spleen is controversial suggesting that it can be mediated by either monosynaptic innervation of the splenic parenchyma or secondary neurons from the celiac ganglion depending on the experimental conditions. Recent physiologic and anatomic studies suggest that inflammation is regulated by neuro-immune multi-synaptic interactions between the vagus and the splanchnic nerves to modulate the spleen. Here, we review the current knowledge on these interactions, and discuss their experimental and clinical implications in infectious and inflammatory disorders.
Conjugation with the small ubiquitin-like modifier (SUMO) constitutes a key post-translational modification regulating the stability, activity, and subcellular localization of its target proteins. ...However, the vast numbers of identified SUMO substrates obscure a clear view on the function of SUMOylation in health and disease. This article presents a comprehensive review on the physiological relevance of SUMOylation by discussing how global SUMOylation levels-rather than specific protein SUMOylation-shapes the immune response. In particular, we highlight the growing body of work on SUMOylation in intestinal pathologies, because of the unique metabolic, infectious, and inflammatory challenges of this organ. Recent studies show that global SUMOylation can help restrain detrimental inflammation while maintaining immune defenses and tissue integrity. These results warrant further efforts to develop new therapeutic tools and strategies to control SUMOylation in infectious and inflammatory disorders.
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